Sickle Cell Patients Have Even Fewer Choices for Pain Relief

By Crystal Lindell

Pfizer is voluntarily taking its sickle cell disease medication Oxbryta (voxelotor) off the market, amid concerns that it could be causing deaths and other complications. Doctors are being told to stop prescribing Oxybryta and to start sickle cell patients on other medications. 

Pfizer said its decision was based on clinical data showing the overall benefits of Oxbryta no longer outweighs the risks. In postmarketing studies, patients taking Oxbryta had higher rates of a vaso-occlusive crisis, a condition that causes severe pain when mis-shaped red blood cells block the flow of blood to tissues and organs. Patients taking the medication also had higher death rates. 

The company said it was also discontinuing all clinical trials of Oxbryta and expanded access programs worldwide. Oxbryta has been on the market since 2019. The medication works by preventing red blood cells from becoming C-shaped and breaking down too quickly.

Pfizer’s announcement delivers another setback to sickle cell patients, who already lack treatment options and face discrimination in the healthcare system. There aren’t many treatments for sickle cell disease (SCD), a lifelong inherited blood disorder that can cause complications starting in early childhood and lead to shortened life expectancy.

The lack of treatments is due in part to the fact that SCD is relatively rare in wealthier countries. It primarily impacts those whose ancestors are from sub-Saharan Africa, an under-served patient population. About 100,000 Americans have SCD, a number so low it discourages drug makers from developing medications to treat it. Over 8 million people worldwide have SCD.

Many sickle cell patients have also borne the brunt of opioid phobia in the United States. They often end up having to go to the ER during pain flares, where many are treated as drug seekers. 

‘This Is a Step Backward’

The National Alliance of Sickle Cell Centers released a statement saying the Pfizer recall was disappointing. But they were glad that Pfizer was re-evaluating Oxbryta to see which SCD patients may still benefit from it..

"At this time, the risks are too great but there may be an opportunity in the future to better understand how to optimize this medication (and all) medications in sickle cell disease,” the organization said. 

It urged sickle cell patients currently taking Oxbryta to make an appointment with their doctor and emphasized that patients should not stop taking the drug abruptly. Instead, they should work out a weaning plan with their care team. 

“Don’t lose faith,” they said. “This is a step backward but we will stay on the path to better outcomes for everyone.”

The organization added that these types of issues highlight the importance of long-term follow-up with a sickle cell center and of clinical registries like GRNDaD, an international registry developed to track the effectiveness of SCD treatments.

“We encourage everyone to see a sickle cell specialist annually to review what is and what is not working for them,” the organization said. “We all know that sickle cell disease is highly variable, many people are different and respond differently to medications. We need to better understand these differences to identify which medication will work best for which people."

An article in MedScape explained that Pfizer’s decision to recall Oxbryta (voxelotor) came amid increased scrutiny of the drug by the European Medicines Agency (EMA). 

EMA began a review of voxelotor in July after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo. Another trial showed a higher  number of deaths than expected. 

Pfizer’s Aida Habtezion, Pfizer’s Chief Medical Officer, said the recall was in the best interest of patients. 

“Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options,” Habtezion said. “We advise patients to contact their physicians to discuss alternative treatment while we continue to investigate the findings from our review of the data.”

Patients, physicians, pharmacists, or other healthcare professionals with questions about Oxbryta should contact Pfizer at 1-800-438-1985.

Direct-to-Consumer Prescription Programs Seem Ripe for Misuse

By Crystal Lindell

Two large pharmaceutical companies have launched websites that help consumers get prescriptions to the medications that they make – and I’m honestly surprised that the entire setup is even legal.

Pfizer launched PfizerForAll in August, while Eli Lilly started LillyDirect back in January. Both websites connect patients with supposedly independent doctors, who can then write prescriptions – for Pfizer or Lilly medications, of course. Both companies will then help facilitate getting the prescription filled, even offering to connect patients with direct-to-home delivery. 

While direct-to-consumer prescriptions may seem like a win for patients – considering how overly complicated and expensive the U.S. healthcare system is – it also seems ripe for misuse. And when it comes to healthcare, that can have serious consequences, up to and including death.

Pfizer says its new website serves patients seeking treatment for migraines, COVID-19 or influenza, as well as adults seeking vaccines for preventable diseases, including COVID, flu, RSV and pneumococcal pneumonia. 

To be more specific, PfizerForAll facilitates patient access to Pfizer medications for migraine, COVID-19 or flu, as well as Pfizer vaccines. Maybe they should just call it AllForPfizer.

Meanwhile, Eli LIlly’s site is for patients seeking treatment for obesity, migraine and diabetes. Like Pfizer’s program, LillyDirect provides access only to “select Lilly medicines.” Maybe they should change the name to DirectToLilly. 

Both companies say their direct-to-consumer programs are designed to make things easier for patients who lack the time, knowledge and resources to manage their own health. 

“People often experience information overload and encounter roadblocks when making decisions for themselves or their family in our complex and often overwhelming U.S. healthcare system. This can be extremely time-consuming and lead to indecision or inaction – and as a result, poor health outcomes,” Aamir Malik, Executive Vice President and Chief U.S. Commercial Officer for Pfizer, said in a press release.

"A complex U.S. healthcare system adds to the burdens patients face when managing a chronic disease. With LillyDirect, our goal is to relieve some of those burdens by simplifying the patient experience to help improve outcomes," David Ricks, Lilly's chair and CEO, said when LillyDirect was launched

To make it easier for patients to buy Pfizer and Lilly products, both companies offer similar amenities. 

PfizerForAll boasts access to same-day doctor appointments; home delivery of prescriptions, over-the-counter drugs and tests; appointment scheduling for vaccines; and even help paying for Pfizer medicines. 

The LillyDirect site is similar. It offers "independent healthcare providers” and home delivery of Lilly medicines through “third-party pharmacy dispensing services." Lilly says its vendors make treatment decisions based on their own “independent medical judgment.”

So, yes, patients will get appointments with supposedly independent doctors. But something tells me the doctors getting booked with patients via Lilly’s website aren’t going to be writing any prescriptions for Pfizer medications. Or vice versa. 

I’m also very skeptical of the claim that doctors aren’t getting any money from the companies directly. Even if they are only getting referrals, that’s more than enough to heavily incentivize doctors to only prescribe medications that those companies make. Especially if the doctors are told that the patient they are seeing was referred to them by the pharmaceutical company itself.

Personally, when I see a doctor, I want them to write prescriptions based on what’s in my best interest – not what’s in the best interest of a pharmaceutical company. Perhaps it's naive and idealistic of me to still believe that doctors are writing prescriptions based solely on a patient’s need for that specific medicine.  

Perhaps healthcare in the United States is already so far beyond that thought process that these new websites aren’t too much of a leap. After all, pharmaceutical companies have long been working hard to influence doctors. So, maybe this is just the next logical step. 

Whenever I go to a makeup store like Ulta, I’m well aware that the seemingly helpful sales clerks are all trying to push me toward a specific lipstick brand. They may even get commissions from the lipstick company for making a sale. 

But, the thing is, what brand of lipstick I wear isn’t a life or death decision. I expect more from companies that make medications. Even if they don’t hold themselves to a higher standard, I expect more from the government regulators who allow this sort of thing. 

Yes, healthcare in the United States is horrific. I know that firsthand. I’m just not convinced that pharmaceutical companies have much interest in helping to fix that. 

Many Covid Patients Can’t Afford Paxlovid

By Arthur Allen, KFF Health News

Evangelical minister Eddie Hyatt believes in the healing power of prayer but “also the medical approach.” So on a February evening a week before scheduled prostate surgery, he had his sore throat checked out at an emergency room near his home in Grapevine, Texas.

A doctor confirmed that Hyatt had covid-19 and sent him to CVS with a prescription for the antiviral drug Paxlovid, the generally recommended medicine to fight covid. Hyatt handed the pharmacist the script, but then, he said, “She kept avoiding me.”

She finally looked up from her computer and said, “It’s $1,600.”

The generally healthy 76-year-old went out to the car to consult his wife about their credit card limits. “I don’t think I’ve ever spent more than $20 on a prescription,” the astonished Hyatt recalled.

That kind of sticker shock has stunned thousands of sick Americans since late December, as Pfizer shifted to commercial sales of Paxlovid. Before then, the federal government covered the cost of the drug.

The price is one reason Paxlovid is not reaching those who need it most. And patients who qualify for free doses, which Pfizer offers under an agreement with the federal government, often don’t realize it or know how to get them.

“If you want to create a barrier to people getting a treatment, making it cost a lot is the way to do it,” said William Schaffner, a professor at Vanderbilt University School of Medicine and spokesperson for the National Foundation for Infectious Diseases.

Public and medical awareness of Paxlovid’s benefits is low, and putting people through an application process to get the drug when they’re sick is a non-starter, Schaffner said. Pfizer says it takes only five minutes online.

It’s not an easy drug to use. Doctors are wary about prescribing it because of dangerous interactions with common drugs that treat cholesterol, blood clots, and other conditions. It must be taken within five days of the first symptoms. It leaves a foul taste in the mouth. In one study, 1 in 5 patients reported “rebound” covid symptoms a few days after finishing the medicine — though rebound can also occur without Paxlovid.

A recent JAMA Network study found that sick people 85 and older were less likely than younger Medicare patients to get covid therapies like Paxlovid. The drug might have prevented up to 27,000 deaths in 2022 if it had been allocated based on which patients were at highest risk from covid. Nursing home patients, who account for around 1 in 6 U.S. covid deaths, were about two-thirds as likely as other older adults to get the drug.

Vaccine Misinformation

Shrunken confidence in government health programs is one reason the drug isn’t reaching those who need it. In senior living facilities, “a lack of clear information and misinformation” are “causing residents and their families to be reluctant to take the necessary steps to reduce covid risks,” said David Gifford, chief medical officer for an association representing 14,000 health care providers, many in senior care.

The anti-vaxxers spreading falsehoods about vaccines have targeted Paxlovid as well. Some call themselves anti-paxxers.

“Proactive and health-literate people get the drug. Those who are receiving information more passively have no idea whether it’s important or harmful,” said Michael Barnett, a primary care physician at Brigham and Women’s Hospital and an associate professor at Harvard, who led the JAMA Network study.

In fact, the drug is still free for those who are uninsured or enrolled in Medicare, Medicaid, or other federal health programs, including those for veterans.

That’s what rescued Hyatt, whose Department of Veterans Affairs health plan doesn’t normally cover outpatient drugs. While he searched on his phone for a solution, the pharmacist’s assistant suddenly appeared from the store. “It won’t cost you anything!” she said.

As Hyatt’s case suggests, it helps to know to ask for free Paxlovid, although federal officials say they’ve educated clinicians and pharmacists — like the one who helped Hyatt — about the program.

“There is still a heaven!” Hyatt replied. After he had been on Paxlovid for a few days his symptoms were gone and his surgery was rescheduled.

About That $1,390 List Price

Pfizer sold the U.S. government 23.7 million five-day courses of Paxlovid, produced under an FDA emergency authorization, in 2021 and 2022, at a price of around $530 each.

Under the new agreement, Pfizer commits to provide the drug for the beneficiaries of the government insurance programs. Meanwhile, Pfizer bills insurers for some portion of the $1,390 list price. Some patients say pharmacies have quoted them prices of $1,600 or more.

How exactly Pfizer arrived at that price isn’t clear. Pfizer won’t say. A Harvard study last year estimated the cost of producing generic Paxlovid at about $15 per treatment course, including manufacturing expenses, a 10% profit markup, and 27% in taxes.

Pfizer reported $12.5 billion in Paxlovid and covid vaccine sales in 2023, after a $57 billion peak in 2022. The company’s 2024 Super Bowl ad, which cost an estimated $14 million to place, focused on Pfizer’s cancer drug pipeline, newly reinforced with its $43 billion purchase of biotech company Seagen. Unlike some other recent oft-aired Pfizer ads (“If it’s covid, Paxlovid”), it didn’t mention covid products.

The other problem is getting the drug where it is needed. “We negotiated really hard with Pfizer to make sure that Paxlovid would be available to Americans the way they were accustomed to,” Department of Health and Human Services Secretary Xavier Becerra told reporters in February. “If you have private insurance, it should not cost you much money, certainly not more than $100.”

‘This Is a Mistake’

Yet in nursing homes, getting Paxlovid is particularly cumbersome, said Chad Worz, CEO of the American Society of Consultant Pharmacists, specialists who provide medicines to care homes.

If someone in long-term care tests positive for covid, the nurse tells the physician, who orders the drug from a pharmacist, who may report back that the patient is on several drugs that interact with Paxlovid, Worz said. Figuring out which drugs to stop temporarily requires further consultations while the time for efficacious use of Paxlovid dwindles, he said.

His group tried to get the FDA to approve a shortcut similar to the standing orders that enable pharmacists to deliver anti-influenza medications when there are flu outbreaks in nursing homes, Worz said. “We were close,” he said, but “it just never came to fruition.”

“The FDA is unable to comment,” spokesperson Chanapa Tantibanchachai said.

Los Angeles County requires nursing homes to offer any covid-positive patient an antiviral, but the Centers for Medicare & Medicaid Services, which oversees nursing homes nationwide, has not issued similar guidance.

“And this is a mistake,” said Karl Steinberg, chief medical officer for two nursing home chains with facilities in San Diego County, which also has no such mandate. A requirement would ensure the patient “isn’t going to fall through the cracks,” he said.

While it hasn’t ordered doctors to prescribe Paxlovid, CMS on Jan. 4 issued detailed instructions to health insurers urging swift approval of Paxlovid prescriptions, given the five-day window for the drug’s efficacy. It also “encourages” plans to make sure pharmacists know about the free Paxlovid arrangement.

Current covid strains appear less virulent than those that circulated earlier in the pandemic, and years of vaccination and covid infection have left fewer people at risk of grave outcomes. But risk remains, particularly among older seniors, who account for most covid deaths, which number more than 13,500 so far this year in the U.S.

Steinberg, who sees patients in 15 residences, said he orders Paxlovid even for covid-positive patients without symptoms. None of the 30 to 40 patients whom he prescribed the drug in the past year needed hospitalization, he said; two stopped taking it because of nausea or the foul taste, a pertinent concern in older people whose appetites already have ebbed.

Steinberg said he knew of two patients who died of covid in his companies’ facilities this year. Neither was on Paxlovid. He can’t be sure the drug would have made a difference, but he’s not taking any chances. The benefits, he said, outweigh the risks.

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Evidence Should Be Updated for Covid-19 Treatment

By Dr. Lynora Saxinger, Undark Magazine

Strong science, particularly vaccine development, helped us steer our way through the Covid-19 pandemic. Now, as the pandemic recedes, it’s time to hold drug companies accountable for the treatments they’ve developed.

The evidence for these medications has not kept pace with major changes in the nature of the Covid-19 pandemic, and updated studies should be required to maintain approval for these very profitable drugs.

The Covid-19 drug development battlefield is littered with 479 failed or inactive drugs, while 358 are still in clinical or preclinical trials, according to a tracker maintained by the Biotechnology Innovation Organization, a trade group.

The only oral Covid-19 therapy approved by the U.S. Food and Drug Administration that is recommended for first line outpatient use is Pfizer’s Paxlovid (nirmatrelvir-ritonavir), a two-drug combination that stops the SARS-CoV-2 virus from replicating in the body.

Hailed as a game changer, Paxlovid is a very good antiviral drug that has saved many lives, and its incredibly rapid development was a feat of science.

The major study leading to its approval, called the EPIC-HR trial, showed that it reduced the risk of hospitalization and death by an impressive 89 percent in high-risk, unvaccinated people.

But there is a lack of high-quality research on how Paxlovid affects outcomes beyond severe Covid — such as duration of illness, how the drug affects transmission, and whether it prevents long Covid. Nevertheless, some physicians are promoting the drug for these uses based on weak, inconsistent data.

pfizer image

The stakes are high: If we fail to set a requirement for well-designed studies of Paxlovid’s impact on all concerns besides hospitalization and death, we will be setting up a slow-moving, disastrous recreation of mistakes made with drugs for other diseases such as influenza.

Early in the Covid-19 pandemic, the explosive, unorganized growth of clinical trials for treatments was intended to save lives from this fearsome new disease. But many trials were small and of low quality, with a few exceptional trials providing much of our good data. In that initial desperate push for Covid-19 treatments, experimental, everything-but-the-kitchen-sink approaches became widely used.

Ivermectin Controversy

The case of ivermectin is instructive: This antiparasitic drug was used in tremendous volumes based on poor quality and sometimes outright fraudulent data, despite advice against its use from the FDA and in formal treatment guidelines. Social media amplification of the increasingly dubious evidence base led to a near-delusional belief in its benefit — and impressive profits for some opportunistic doctors.

A few well-coordinated and well-designed trials up front would have shortened the controversy, saved costs, and avoided duplicated effort of smaller low-quality trials. Most importantly, showing it to be ineffective earlier may have prevented the ensuing social media crusade, perhaps allowing some high-risk people to accept evidence-supported treatments like Paxlovid and the intravenous antiviral remdesivir rather than requesting, or even suing hospitals, to administer ivermectin.

Covid-19’s infection outcomes changed unusually rapidly across waves of the pandemic, which meant that studies could be outdated in months if they did not reflect the current viral strains and population immune responses. Data collection in the EPIC-HR study, which still guides treatment with Paxlovid, took place in 2021 when hospitalization rates were high, many were unvaccinated (including all trial participants), the viral strains were different than today, and the main outcome of interest in many communities was “flattening the curve,” or preventing hospitalization.

Now, almost everyone has been vaccinated, infected, or both. In a recent study, 96.4 percent of U.S. blood donors had Covid-19 antibodies by September 2022. The overall risk of hospitalization and death has also decreased significantly.

A Different Disease

Essentially, we are now dealing with a different disease. We are more focused on outcomes such as time lost from work, transmission risk, and long Covid risk. Yet there is almost no direct evidence about Paxlovid’s effect on these outcomes.

Paxlovid was approved for the treatment of mild to moderate Covid-19 in adults at high risk of developing severe disease. However, physicians and pharmacists have told me, it is increasingly being prescribed off-label for lower risk patients. This contention is supported by a recent U.S.-based preprint showing that 42 percent of more than 111,000 Paxlovid recipients had no major medical comorbidities, with treatment eligibility defined by having at least one risk factor for severe Covid-19.

Some physicians are extrapolating from hamster studies and lab data to suggest it reduces Covid-19 transmission. And they’re prescribing it to reduce long Covid risk based on very weak studies that analyzed administrative databases for Covid-19 complications rather than tracking long Covid symptoms in treated and untreated patients.

This matters because Paxlovid treatment for people who are not high risk has not shown significant benefit. One still unpublished randomized trial of lower-risk patients was terminated because low rates of hospitalization overall (in treated and untreated people) made it impossible to see a benefit.

Even in higher-risk groups, a recent meta-analysis of observational studies has shown very little absolute reduction of mortality, and no benefit in such patients under age 60. At the same time, people taking Paxlovid face possible side effects, drug interactions, and volatile drug pricing. They do not know if Paxlovid is worth all of that. They don’t know if the drug will reduce transmission to others, if they are less likely to get severely ill, if they will need time off work, or if it will spare them from long Covid.

Tamiflu Questions

Infectious diseases specialists like myself are experiencing an alarming sense of déjà vu. Tamiflu (oseltamivir), a treatment for influenza, was licensed in 1999 with data showing a modest benefit in reducing illness by one day. The reviewers noted that a “more definitive demonstration of clinical or public health relevance” would require additional data.

But 24 years later, we are not farther ahead — important questions about Tamiflu remain unanswered, with longstanding debates about the benefit of the drug and a false advertising lawsuit that went on for nearly 10 years before being dropped in July. The guidelines for the use of Tamiflu in influenza vary tremendously because of varied interpretation of a poor evidence base, and newer studies call its use as an influenza treatment into question. Even so, in its first 15 years on the market, Tamiflu made $18 billion in sales.

It is hard to stop a prescribing practice once it has become the norm, despite inadequate data. This is a recognized driver of cost increases in health care.

Pharmaceutical companies play a pivotal role in the research and development of effective therapies, and their lifesaving contributions during the Covid-19 pandemic have been commendable. However, the major investments these companies make in R&D should not give them free rein to market high-cost, high-volume drugs of public health importance without continued scrutiny of their effectiveness if the initial registration studies no longer stand because of changes in the disease.

Some bold, novel options could help address this gap in evidence. In exceptional circumstances (such as pandemics), pharmaceutical companies could be required to conduct studies to reassess a drug’s effectiveness after it has entered the market if conditions have meaningfully changed since the initial trials.

Another option could require companies to put a small portion of drug profits towards funding well-designed, independent trials so that crucial, commercially successful drugs would be part of ongoing studies. The FDA and other agencies should judiciously require and support such studies that could help guide treatment decisions, while balancing the need to support appropriate research and new drug development.

The medical community has responsibility, too: Professional societies that draft treatment guidelines must take a more consistently assertive stance in advising against uses for which there is insufficient evidence, rather than leaving it open to prescriber judgment. Both prescribers and potential patients need to accept and use evidence to help sustain health care systems, and lobby for changes needed to define the best treatments for people with Covid-19.

We are at a unique juncture in the fight against Covid-19, as fear gives way to complacency — and the path forward is scientific rigor. Failing to mandate high-quality evidence for treatment choices may lead us back down the path of inadequately researched treatments, opinion-driven guidelines, and wasted resources.

Pfizer has raked in about $20 billion dollars in revenue from Paxlovid alone over the last two years. This sum is nearly half of the National Institutes of Health’s entire budget for 2022. It is not surprising that the company has not voluntarily started additional trials after approval based on the stellar results in that first, now-irrelevant trial.

In the wake of the pandemic, we have an opportunity to improve both what we are doing, and how we may address research challenges in a future crisis. Paxlovid’s price is set to increase — from $530 to $1,390 before insurance — next year, but there is no corresponding increase in our knowledge of its value. The cost of this information gap will be very high, for both individuals and health care systems.

Lynora Saxinger, MD, is a journalist, infectious disease physician, and professor at the University of Alberta who headed a Covid evidence synthesis group during the pandemic. She is currently a Fellow in Journalism and Health Impact at the Dalla Lana School for Public Health.

This article was originally published by Undark, a non-profit, editorially independent online magazine covering the complicated and often fractious intersection of science and society. You can read the original article here.

FDA Approves Nasal Spray That Relieves Migraine in Minutes

By Pat Anson, PNN Editor

Pfizer will soon launch a fast-acting nasal spray that can relieve migraine pain in as little as 15 minutes for some patients. The company has received FDA approval for Zavzpret (zavegepant), the first calcitonin gene-related peptide (CGRP) inhibitor formulated into a nasal spray for the acute treatment of migraine in adults with or without aura.    

“When a migraine hits, it has a significant negative impact on a person’s daily life,” Kathleen Mullin, MD, Associate Medical Director at New England Institute for Neurology & Headache, said in a Pfizer press release. “Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, Zavzpret offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly.”

That’s the good news. The bad news is how expensive the nasal spray is likely to be when it becomes available in July 2023. According to a Pfizer spokesperson, Zavzpret “is expected to be comparable in price to other FDA approved CGRP migraine medicines.”

CGRP is a protein that binds to nerve receptors in the brain and dilates blood vessels, causing migraine pain. Since their introduction in 2018, CGRP inhibitors have become the biggest innovation in migraine treatment in decades, although their cost is prohibitive for many patients.

Eight doses of Nurtec, a CGRP-inhibiting tablet taken daily to prevent and treat migraine, can cost over $1,000, while the listed price for Emgality, a CGRP-inhibiting solution, is $679 for a self-injectable syringe used once a month for migraine prevention. Prices will vary for patients, depending on their insurance and whether they qualify for a patient assistance program.

In a Phase 3 study involving over 1,400 patients, recently published in The Lancet Neurology, a single 10mg dose of Zavzpret relieved migraine pain in as little as 15 – 30 minutes, and provided sustained relief for as long as 48 hours.  

An important caveat is that the nasal spray did not help everyone. Only 22.5% of patients were pain free after two hours, compared to 15.5% who were given a placebo.

The 7% difference may sound like marginal improvement in a minority of patients, but in the parlance of clinical trials it’s considered “statistically significant” improvement.  

Zavzpret was well tolerated by most patients. The most common adverse reactions after ingesting the spray were taste disorders (dysgeusia and ageusia), nausea, nasal discomfort and vomiting.

PFIZER IMAGE

“The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications,” said Angela Hwang, Chief Commercial Officer and President of Pfizer’s Global Biopharmaceuticals Business.

Migraine affects about 39 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

If Covid Vaccines Are So Effective, Why Do I Need a Booster Shot?

By Julie Appleby, Kaiser Health News

The politicization of covid vaccines — and just about everything else having to do with the pandemic — has led to confusion, if not utter fatigue.

And some posts circulating on social media — like this slickly edited piece on YouTube — seem to build on these feelings, attempting to cast doubt on the effectiveness of the vaccines.

The video intersperses comments from White House medical adviser Dr. Anthony Fauci extolling their protectiveness with screenshots of news headlines, starting with those citing 100% effectiveness, then moving through others reporting sharply lower percentages. Set to the rapidly increasing tempo of the orchestral piece “In the Hall of the Mountain King,” the video ends with headlines about drug company profits.

But slowing the video to parse the headlines reveals more complexity. Some are reporting on studies that looked only at infection rates; others, more serious outcomes, including hospitalization and death. Some are about vaccines not offered in the U.S. In short, the video fosters misperceptions by mixing together dissimilar data points and leaving out key details.

Still, one can’t help but wonder what’s really going on with effectiveness — and is any of it a surprise?

If you don’t read any further, know this: No vaccine is 100% effective against any disease. The covid shots are no exception. Effectiveness in preventing infection — defined as a positive test result — appears in some studies to wane sharply the more time that goes by after completing the one- or two-shot regimen.

But on key measures — prevention of serious illness, hospitalization and death — real-world studies from the U.S. and abroad generally show protection weakening slightly, particularly in older or sicker people, but remaining strong overall, even with the rise of the more infectious delta variant of the covid virus.

The bottom line? Getting vaccinated with any of the three vaccines available in the U.S. reduces the chance of getting infected in the first place, and significantly cuts the risk of hospitalization or death if you do contract covid-19. The Centers for Disease Control and Prevention recently published a study showing fully vaccinated people were more than 10 times less likely to die or be hospitalized than the unvaccinated.

“When it comes to what matters, vaccines hold up really well,” said Dr. Amesh Adalja, an infectious-disease physician and senior scholar at the Johns Hopkins Center for Health Security. “They were designed to tame the virus.”

What do “efficacy” and “effectiveness” really mean?

Before a drug or vaccine is greenlighted by federal regulators, it is tested on volunteers randomly assigned to get either the product or a placebo. Then researchers compare how the groups fare. In the case of a vaccine, they look at how well it prevents infection, and whether it protects against serious illness, hospitalization or death. Those clinical trial results are often referred to as efficacy measures.

In the real world, however, a drug or vaccine’s performance is affected by numerous factors, including a much larger population receiving it, some of whom have underlying conditions or socioeconomic circumstances different from those in the clinical trial. That real-world performance measure is called effectiveness.

When authorized for emergency use following clinical trials, both the Pfizer-BioNTech and Moderna two-dose vaccines reported efficacy against symptomatic illness in the mid-90% range. The Johnson & Johnson single-dose shot — which was tested later, when there were more variants — reported overall efficacy in the high 60% range.

So, all three vaccines exceeded the 50% threshold health officials sought as a minimum for efficacy. Keep in mind, also, that the annual influenza vaccine’s real-world effectiveness is often 40% to 50%.

Another point: 95% effectiveness doesn’t mean 95% of vaccinated people will never get infected. What it means is that a fully vaccinated person exposed to the virus faces only 5% of the risk of infection compared with an unvaccinated person.

Have the effectiveness numbers changed?

Yes, decline in effectiveness against infection is seen in some studies. A few have also raised concerns that protection against serious illness may also be diminished, particularly in older people and patients with underlying medical conditions.

Reasons for the decline vary. First, when the vaccines were authorized, much of the U.S. was under tighter pandemic-related stay-at-home rules. Nearly a year later, restrictions — including mask rules — have loosened in many areas. More people are traveling and going into situations they would have avoided a year ago. So, exposure to the virus is higher.

Some studies from the U.S. and abroad show that time elapsed since vaccination also plays a role. The Lancet recently published a study of more than 3.4 million Kaiser Permanente members, both vaccinated and not, reviewing the effectiveness of the Pfizer vaccine. It showed an overall average 73% effectiveness against infection during the six months after inoculations, and an overall 90% effectiveness against hospitalization.

But protection against infection declined from 88% in the month after full vaccination to 47% at five to six months. Time since vaccination played a larger role than any changes in the virus itself, the researchers concluded.

“It shows vaccines are highly effective over time against severe outcomes,” said lead author Sara Tartof, an epidemiologist with the Department of Research and Evaluation for Kaiser Permanente Southern California. “Against infection, it does decline over time, something that is not unexpected. We have boosters for many other vaccines.”

The virus, too, has mutated.

“Along came delta,” said Dr. William Schaffner, a professor of preventive medicine at Vanderbilt University School of Medicine. “Because this virus was so highly contagious, it changed the outcomes slightly.”

And some vaccinated people can fall seriously ill with covid, or even die, especially if they have an underlying medical problem, as was the case with Gen. Colin Powell. He died of covid complications even though he was fully vaccinated — likely because he also had a blood cancer called multiple myeloma, which can lower the body’s response to an invading virus as well as to vaccination.

Why are they recommending booster shots?

Most scientists, researchers and physicians say the vaccines are working remarkably well, especially at preventing serious illness or death. But it’s not unusual to need more than one dose.

Vaccines for shingles and measles both require two shots, while people need to be revaccinated against tetanus every 10 years. Because influenza varies each year, flu shots are annual.

Immune response is often better when vaccines are spaced apart by a few months. But during the rollout of the covid vaccines, so many people were falling ill and dying of covid each day that the Food and Drug Administration and CDC decided not to delay, but to authorize the first and second doses within about a month of each other.

“We learn as we go along,” said Schaffner. “It was always anticipated there might have to be follow-up doses.”

Now, the recommendations call for a second dose for anyone who received a J&J shot at least two months prior. For those who received the two-dose Pfizer or Moderna vaccine, the recommendation is to wait six months after the second dose to get a booster, which is currently recommended for those who are 65 and older; have any of a variety of underlying health conditions; live in congregate settings, such as nursing homes; or have jobs that put them at higher risk. The booster recommendations may expand in the coming months.

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

Experts Debate Need for Covid Booster Shots

By Rachana Pradhan, Kaiser Health News

The Biden administration’s plans to make covid-19 booster shots available next month has drawn a collective scream of protest from the scientific community.

As some scientists see it, the announcement is rash and based on weak evidence, and they worry it could undercut confidence in vaccines with no clear benefit of controlling the pandemic. Meanwhile, more information is needed on potential side effects or adverse effects from a booster shot, they say.

Perhaps even worse, the announcement has fueled deeper confusion about what Americans need to do to protect themselves from covid.

“I think we’ve scared people,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and an adviser to the National Institutes of Health and the Food and Drug Administration.

“We sent a terrible message,” he said. “We just sent a message out there that people who consider themselves fully vaccinated were not fully vaccinated. And that’s the wrong message, because you are protected against serious illness.”

As of Thursday, 51% of the U.S. population was fully vaccinated, Centers for Disease Control and Prevention data shows. Biden administration officials ― citing data from Israel, a study from the Mayo Clinic that is not yet peer-reviewed and new CDC studies ― say it’s necessary to plan for boosters to prevent a worsening of the pandemic as the delta variant powers a surge in cases and overwhelms hospital intensive care units.

In essence, officials are caught between a rock and a hard place ― trying to be prepared while simultaneously not undermining messaging about how well the existing vaccines work.

Virus Unpredictable

Officials must weigh two unknowns: the risks of moving ahead aggressively with booster shots versus the risks of waiting to learn much more about the virus and the power of the vaccines. The government’s normal path to regulatory approval is, by design, slow and deliberate. The virus has its own schedule, fast and unpredictable.

“Arguably, I think that the federal government is simply trying to stay ahead of the curve,” said Dr. Joshua Barocas, associate professor of medicine at the University of Colorado. But, he said, “I have not seen robust data yet to suggest that it is better to boost Americans who have gotten two vaccines than invest resources and time in getting unvaccinated people across the world vaccinated.”

Beginning in late September, boosters would be made available to adults (age 18 and up) eight months after they received the second dose of a Pfizer-BioNTech or Moderna covid vaccine, President Joe Biden said. But his plan comes with big caveats: It does not yet have the blessing of a CDC advisory panel, and the FDA has not authorized boosters for all adults.

The urgent question is whether the vaccines are losing their power against covid.

“We are concerned that this pattern of decline we are seeing will continue in the months ahead, which could lead to reduced protection against severe disease, hospitalization and death,” Surgeon General Vivek Murthy said.

But many scientists and public health experts say the data doesn’t demonstrate a clear benefit to the public in making booster shots widely available, and the Biden administration’s message confuses people about what the covid vaccines were designed to do.

“They’re not a force field. They don’t repel the virus from your body. They train your immune system to respond when you become infected … with the goal of keeping you out of the hospital,” said Jennifer Nuzzo, an epidemiologist and associate professor at the Johns Hopkins Bloomberg School of Public Health.

Meanwhile, questions abound. Will boosters for fully vaccinated adults make the virus less transmissible ― that is, slower or less likely to spread to others?

“I certainly hope that’s the case … but the bottom line, with full transparency, we don’t know that right now,” Dr. Anthony Fauci, Biden’s chief medical adviser, said Wednesday.

What about side effects? “It would be nice to understand what side effects people have after their third dose,” Nuzzo said.

“We don’t have any reason to believe, based on the safety profile of the vaccine itself, that we’re going to see significant adverse events with booster shots,” Barocas said. However, those things are “just now being studied.”

The concerns are real. While serious side effects from covid vaccines have been rare, some have caused alarm ― including mRNA vaccines being linked to cases of myocarditis, or inflammation of the heart.

“At the individual level, we need to know the side effect profile of a 3rd dose, especially in younger people. Until now, the benefits of vaccination have far outweighed the potential side effects,” Dr. Jeremy Faust, an emergency medicine physician at Brigham and Women’s Hospital in Boston, wrote in a blog post outlining why he was skeptical about a plan to give boosters to everyone.

Vaccines Still Effective

Even in light of the new CDC studies published Wednesday, experts say one thing is clear: The vaccines still work very well at what they were meant to do, which is to protect people against the worst outcomes of getting infected with the virus.

One study, relying on data from 21 hospitals in 18 states, found no significant change in the vaccines’ effectiveness against hospitalization between March and July, which coincides with delta becoming the prevalent covid strain. Another, using data from New York, also found the vaccines highly effective in preventing hospitalization, even as there was a decline in effectiveness against new infections. The third, evaluating the Pfizer and Moderna vaccines in nursing home residents, saw a drop in how effective they were at preventing infection ― but the research didn’t distinguish between symptomatic and asymptomatic cases.

“It’s like we’re engaged in friendly fire against these vaccines,” Nuzzo said. “What are we trying to do here? Are we just trying to reduce overall transmission? Because there’s no evidence that this is going to do it.”

Fauci, in outlining the case for boosters, highlighted data showing that antibody levels decline over time and higher levels of antibodies are associated with higher vaccine efficacy. But antibodies are only one component of the body’s defense mechanisms against a covid infection.

When the antibodies decrease, the body compensates with a cellular immune response. “A person who has lost antibodies isn’t necessarily completely susceptible to infection, because that person has T-cell immunity that we can’t measure easily,” said Dr. Cody Meissner, a specialist in pediatric infectious diseases who sits on the FDA’s vaccine advisory panel.

John Wherry, director of the Penn Institute of Immunology at the University of Pennsylvania, recently published a study finding that the mRNA vaccines provoked a strong response by the immune system’s T cells, which researchers said could be a more durable source of protection. Wherry is working on a second study based on six months of data.

“We’re seeing very good durability for at least some components of the non-antibody responses generated by the vaccines,” he said.

For protection against serious disease, “really all you need is immunological memory, and these vaccines induce immunological memory and immunological memory tends to be longer-lived,” Offit said. Federal scientists also are studying T-cell response, Fauci said.

FDA Approval Needed

Pfizer and Moderna have said they think boosters for covid will be necessary. But it’s up to the government to authorize them. Federal officials say they are sifting through new data from the companies and elsewhere as it becomes available.

There’s not a deep playbook for this: Emergency use authorization, or EUA, of vaccines has been sparingly used. The FDA has already amended Pfizer’s prior EUA clearance twice, first in May to expand the vaccines to adolescents 12 to 15 years old and, again, this month to allow immunocompromised people to obtain a third dose. The FDA did not respond to questions about the process for authorizing widespread booster shots.

Pfizer announced in July that it expects $33.5 billion in covid vaccine revenue this year. Its stock has risen 33% this year, closing at $48.80 Thursday. Moderna reported sales of $5.9 billion through June 30 for 302 million doses of its vaccine. The company’s stock has skyrocketed 236% year-to-date, closing at $375.53 Thursday.

In applying for emergency authorization, the FDA requires vaccine manufacturers to submit clinical efficacy data and all safety data from phase 1 and phase 2 clinical trials as well as two months of safety data from phase 3 studies. For full approval, the FDA requires manufacturers to submit six months of data.

Pfizer this week announced it has submitted phase 1 clinical trial data to the FDA as part of an evaluation for future approval of a third dose. The company said phase 3 results are “expected shortly.”

Pfizer said its preliminary trial results showed a third dose was safe and increased antibody levels against the original virus and the delta variant. Moderna found a third dose had safety results similar to a second dose and produced a strong antibody response. 

Typically, any distribution of shots would occur after the CDC’s Advisory Committee on Immunization Practices also developed recommendations. But with the Biden administration’s announcement about boosters, public health experts worry the message suggests the outcome is preordained.

“They have completely and unfairly jammed FDA and ACIP. They’ve left them no choice. If there’s no booster program, FDA gets blamed and that’s not appropriate,” said Dr. Nicole Lurie, a former senior Health and Human Services official in the Obama administration and U.S. director of the Coalition for Epidemic Preparedness Innovations, the global epidemic vaccines partnership.

Kaiser Health News is a national health policy news service. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

FDA Panels Say New Arthritis Drug Too Risky

By Pat Anson, PNN Editor

Two FDA advisory committees have voted against recommending an experimental non-opioid pain reliever as a new treatment for osteoarthritis, dealing a potential death blow to a drug that’s been under development for 15 years.

On a nearly unanimous 19 to 1 vote, the FDA’s Arthritis Advisory Commitee and Drug Safety and Risk Management Advisory Committee decided that the benefits of tanezumab do not outweigh its possible safety risks, which include the acceleration of osteoarthritis in some patients.  Advisory committee recommendations are not binding on the FDA, but they are likely to carry a good deal of weight when the agency makes a final decision on tanezumab.

Pfizer and Eli Lilly are jointly developing tanezumab, an injectable humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases in the body due to injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

FDA reviewers released a report this week saying tanezumab works as a pain reliever, but the effect “is modest, and there is no convincing evidence of a superior efficacy” over non-steroidal anti-inflammatory drugs (NSAIDs), the current standard treatment for osteoarthritis.

More concerning are the potential side effects of tanezumab, the most serious being rapidly progressing osteoarthritis that is so severe some patients need total joint replacements. Investigators say tanezumab also appears to affect healthy joints and causes “abnormal peripheral sensation” similar to carpal tunnel syndrome.

The side effects of tanezumab have been known for over a decade. The FDA slowed the development of tanezumab and other NGF inhibitors in 2010 because of concerns they make osteoarthritis worse in some patients.

Under pressure to approve more non-opioid pain relievers, the FDA allowed clinical studies of tanezumab to resume in 2015 and two years later gave it “fast track” designation to help speed its development.

Pfizer and Eli Lilly have conducted dozens of clinical trials evaluating the safety and efficacy of tanezumab on more than 18,000 patients. The companies at one time considered, but then abandoned plans to develop tanezumab as a treatment for chronic low back pain after 10% of patients given high doses developed joint pain and other side effects.

Critics say its time to finally throw in the towel on tanezumab.

“The drug is unsafe. It accelerates the underlying joint disease. And according to the FDA, even if you stop the drug early on, there’s evidence you can still progress to having these joint problems,” Michael Carome, director of Public Citizen’s Health Research Group, told PNN.  “The decision here is clear cut. The drug should not be approved. And in our view, no further studies on this drug should be done. Because it would be unethical to continue to expose people to this drug where the harm is clear and there’s no real benefit.”

A Pfizer spokesman said the company would continue to seek approval for tanezumab, despite the committees’ recommendation.

“While we are disappointed in today’s outcome, we continue to believe that the clinical data presented for tanezumab supports its benefit-risk profile,” Jim Rusnak, chief development officer for Pfizer, said in a statement. “The patients whom we aim to help with tanezumab are suffering from significant, debilitating osteoarthritis pain and have exhausted available medical therapies and are hopeful for new, non-opioid treatments. We will continue to work with the FDA to determine next steps.”

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine. The World Health Organization estimates that about 10% of men and 18% of women over age 60 have some form of osteoarthritis.

Don't Get Picky: All Three Covid Vaccines Highly Effective

By Arthur Allen and Liz Szabo, Kaiser Health News

When getting vaccinated against Covid-19, there’s no sense being picky. You should take the first authorized vaccine that’s offered, experts say.

The newest Covid vaccine on the horizon, from Johnson & Johnson, is probably a little less effective at preventing sickness than the two shots already being administered around the U.S., from Pfizer-BioNTech and Moderna.

The Food and Drug Administration authorized the Johnson & Johnson vaccine after reporting it showed about 66% effectiveness at preventing Covid illness in a 45,000-person trial. No one who received the vaccine was hospitalized with or died of the disease, according to the data released by the company and FDA. As many as 4 million doses could be shipped out of J&J’s warehouses beginning this week.

The J&J vaccine is similar to the shots from Moderna and Pfizer-BioNTech, but uses a different strategy for transporting genetic code into human cells to stimulate immunity to the disease. The Moderna and Pfizer-BioNTech vaccines were found in trials last fall to be 94% effective in preventing illness caused by Covid. They also prevented nearly all severe cases.

But the difference in those efficacy numbers may be deceptive. The vaccines were tested in different locations and at different phases of the pandemic. And J&J gave subjects in its trial only one dose of the vaccine, while Moderna and Pfizer have two-dose schedules, separated by 28 and 21 days, respectively. The bottom line, however, is that all three do a good job at preventing serious Covid.

“It’s a bit like, do you want a Lamborghini or a Chevy to get to work?” said Dr. Gregory Poland, director of the Mayo Clinic’s Vaccine Research Group, who was a paid consultant in the J&J study. “Ultimately, I just need to get to work. If a Chevy is available, sign me up.”

“From a personal and public health perspective, the best advice for now is to get whatever you can as soon as you can get it, because the sooner we all get vaccinated the better off we all are,” said Dr. Norman Hearst, a family doctor and epidemiologist at the University of California-San Francisco.

Of the 10 people who got severe disease in the Pfizer trial, nine had received a placebo, or fake vaccine; none of the 30 severe cases in the Moderna trial occurred in people who got the true vaccine. A month after receiving the Johnson & Johnson shot there were no deaths or hospitalizations in those who had been vaccinated.

“The real goal is to keep people out of the hospital and the ICU and the morgue,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “This vaccine will do that well.”

J&J Vaccine Tested Against Variants

The data that Moderna and Pfizer-BioNTech presented to the FDA for their vaccines came from large clinical trials that took place over the summer and early fall in the United States. At the time, none of the new variants of Covid — some of which may be better at evading the immune responses produced by vaccines — were circulating here.

In contrast, the J&J trial began in September and was put into the arms of people in South America, South Africa and the United States. The J&J vaccine was 72% effective against moderate to severe Covid in the U.S. part of the trial, compared with 57% in South Africa, where a more contagious mutant virus is the dominant strain.

The Moderna and Pfizer-BioNTech vaccines might not have gotten the same sparkling results had they been tested more recently — or in South Africa.

“This vaccine was tested in the pandemic here and now,” said Dr. Dan Barouch, a Harvard Medical School professor whose lab at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston developed the J&J vaccine. “The pandemic is a much more complex pandemic than it was several months ago.”

The J&J vaccine appears to have some other advantages. First, it seems to cause fewer serious side effects like the fever and malaise suffered by some Pfizer-BioNTech and Moderna vaccine recipients. High fever and dehydration are particular concerns in fragile elderly people who “have one foot on the banana peel,” said Dr. Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program. The J&J vaccine “may be a better vaccine for the infirm.”

Many people may prefer the J&J shot because “it’s one and done.” It’s easier for administrators too: just one appointment to schedule.

The J&J vaccine can also be stored in regular refrigerators, while the Pfizer and Moderna vaccines have to be stored in freezers and must be used or discarded within six hours after the vial is opened. Vials of the J&J vaccine can be restored in a refrigerator for later use if doses remain.

“Right now we have mass immunization clinics that are open but have no vaccine,” said Offit. “Here you have a single-dose regime with easy storage and handling.”

Ultimately, a person’s address — not their personal preference — may determine which vaccine they receive, said E. John Wherry, director of the Institute for Immunology at the University of Pennsylvania’s Perelman School of Medicine. He pointed out that the Johnson & Johnson vaccine is a simpler choice for rural areas.

“A vaccine doesn’t have to be 95% effective to be an incredible leap forward,” said Wherry. “When we get to the point where we have choices about which vaccine to give, it will be a luxury to have to struggle with that question.”

Kaiser Health News is a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.

If I Have MS or an Autoimmune Condition, Should I Get the Covid Vaccine?

By Judith Graham, Kaiser Health News

As public demand grows for limited supplies of covid-19 vaccines, questions remain about the vaccines’ appropriateness for older adults with various illnesses, including those with cancer, multiple sclerosis or autoimmune conditions.

Recently, a number of readers have asked me whether older relatives with these conditions should be immunized. This is a matter for medical experts, and I solicited advice from several. All strongly suggested that people with questions contact their doctors and discuss their individual medical circumstances.

Experts’ advice may be helpful since states are beginning to offer vaccines to adults over age 65, 70 or 75, including those with serious underlying medical conditions. Twenty-eight states are doing so, according to the latest survey by The New York Times.

Q: My 80-year-old mother has chronic lymphocytic leukemia. Should she get vaccinated?

First, some basics. Older adults, in general, have responded extremely well to the two covid-19 vaccines that have received special authorization from the Food and Drug Administration. In large clinical trials sponsored by drug makers Pfizer and Moderna, the vaccines achieved substantial protection against significant illness, with efficacy for older adults ranging from 87% to 94%.

But people 65 and older undergoing cancer treatment were not included in these studies. As a result, it’s not known what degree of protection they might derive.

Dr. Tobias Hohl, chief of the infectious diseases service at Memorial Sloan Kettering Cancer Center in New York City, suggested that three factors should influence patients’ decisions: Are vaccines safe, will they be effective, and what is my risk of becoming severely ill from covid-19?

Regarding risk, he noted that older adults are the people most likely to become severely ill and perish from covid, accounting for about 80% of deaths to date — a compelling argument for vaccination.

Regarding safety, there is no evidence at this time that cancer patients are more likely to experience side effects from the Pfizer-BioNTech and Moderna vaccines than other people. “We are confident that these vaccines are safe for [cancer] patients,” including older patients, said Dr. Armin Shahrokni, a Memorial Sloan Kettering geriatrician and oncologist.

The exception, which applies to everyone, not just cancer patients: people who are allergic to covid-19 vaccine components or who experience severe allergic responses after getting a first shot shouldn’t get covid-19 vaccines.

In new guidelines published late last week, the National Comprehensive Cancer Network, an alliance of cancer centers, urged that patients undergoing active treatment be prioritized for vaccines as soon as possible. A notable exception:  Patients who’ve received stem cell transplants or bone marrow transplants should wait at least three months before getting vaccines, the group recommended.

The American Cancer Society’s chief medical and scientific officer, Dr. William Cance, said his organization is “strongly in favor of cancer patients and cancer survivors getting vaccinated, particularly older adults.”

Q: Should my 97-year-old mom, in a nursing home with dementia, get the covid vaccine?

The federal government and all 50 states recommend covid vaccines for long-term care residents, most of whom have Alzheimer’s disease or other types of cognitive impairment. This is an effort to stem the tide of covid-related illness and death that has swept through nursing homes and assisted living facilities — 37% of all covid deaths as of mid-January.

The Alzheimer’s Association also strongly encourages immunization against covid-19, “both for people [with dementia] living in long-term care and those living in the community, said Beth Kallmyer, vice president of care and support.

Minimizing suffering is a key consideration, said Dr. Michael Rafii, associate professor of clinical neurology at the University of Southern California’s Keck School of Medicine.

“Even if a person has end-stage dementia, you want to do anything you can to reduce the risk of suffering. And this vaccine provides individuals with a good deal of protection from suffering severe covid,” he said. “My advice is that everyone should get vaccinated, regardless of what stage of dementia they’re in.”

Q: I’m 80 and I have Type 2 diabetes and an autoimmune disease. Should I get the vaccine?

There are two parts to this question. The first has to do with “comorbidities” — having more than one medical condition. Should older adults with comorbidities get covid vaccines?

Absolutely, because they’re at higher risk of becoming seriously ill from covid, said Dr. Abinash Virk, an infectious diseases specialist and co-chair of the Mayo Clinic’s covid-19 vaccine rollout.

“Pfizer’s and Moderna’s studies specifically looked at people who were older and had comorbidities, and they showed that vaccine response was similar to [that of] people who were younger,” she noted.

The second part has to do with autoimmune illnesses such as lupus or rheumatoid arthritis, which also put people at higher risk. The concern here is that a vaccine might trigger inflammatory responses that could exacerbate these conditions.

Philippa Marrack, chair of the department of immunology and genomic medicine at National Jewish Health in Denver, said there’s no scientifically rigorous data on how patients with autoimmune conditions respond to the Pfizer and Moderna vaccines.

So far, reasons for concern haven’t surfaced. “More than 100,000 people have gotten these vaccines now, including some who probably had autoimmune disease, and there’s been no systematic reporting of problems,” Marrack said. If patients with autoimmune disorders are really worried, they should talk with their physicians about delaying immunization until other covid vaccines with different formulations become available, she suggested.

Last week, the National Multiple Sclerosis Society recommended that most patients with multiple sclerosis — another serious autoimmune condition — get the Pfizer or Moderna covid vaccines.

“The vaccines are not likely to trigger an MS relapse or to worsen your chronic MS symptoms. The risk of getting COVID-19 far outweighs any risk of having an MS relapse from the vaccine,” it said in a statement.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

What to Expect When COVID Vaccines Roll Out

By Judith Graham, Kaiser Health News

Vaccines that protect against COVID-19 are on the way. What should older adults and people with chronic illness expect? Will there be enough doses for everyone who wants to be vaccinated?

The first vaccine candidates, from Pfizer and Moderna, could arrive before Christmas, according to Alex Azar, who heads the Department of Health and Human Services.

Both vaccines are notably effective in preventing illness due to the coronavirus, according to information released by the companies, although much of the data from clinical trials is still to come. Both have been tested in adults age 65 and older, who mounted a strong immune response.

Seniors in nursing homes and assisted living centers will be among the first Americans vaccinated, following recommendations last week by a federal advisory panel. Older adults living at home will need to wait a while longer.

Many uncertainties remain. Among them: What side effects can older adults anticipate and how often will these occur? Will the vaccines offer meaningful protection to seniors who are frail or have multiple chronic illnesses?

Here’s a look at what’s known, what’s not and what lies ahead.

Timetable for Vaccines

Pfizer’s vaccine will be evaluated by a 15-member Food and Drug Administration advisory panel on Thursday. Moderna’s vaccine is expected to go before the panel Dec. 17.

At least two days before each meeting, an analysis by FDA staff will be made public. This will be the first opportunity to see extensive data about the vaccines’ performance in large phase 3 clinical trials, including more details about their impact on older adults.

So far, summary results disclosed in news releases indicate that Pfizer’s vaccine, produced in partnership with BioNTech, has an overall efficacy rate of 95% and efficacy of 94% in people 65 and older. Moderna’s overall efficacy is 94%, with 87% efficacy in preventing moderate disease in older adults, according to Moncef Slaoui, chief science adviser to Operation Warp Speed, the government’s COVID-19 vaccine development program.

If the advisory panel gives a green light, the FDA will decide within days or weeks whether to authorize the Pfizer and Moderna vaccines for emergency use. Distribution of the vaccine has already begun, and health care providers are expected to begin administering it immediately after the FDA acts.

Who Gets Vaccinated First?

At a Dec. 1 meeting of the Advisory Commission on Immunization Practices (ACIP), which guides the Centers for Disease Control and Prevention on vaccines, experts recommended that people living in long-term care (primarily nursing homes and assisted living facilities) and health care workers be the first groups to get COVID-19 vaccines.

This recognizes the extraordinary burden of COVID-19 in long-term care facilities. Although their residents represent fewer than 1% of the U.S. population, they account for 40% of COVID deaths — more than 100,000 deaths to date.

The commission’s decision comes despite a lack of evidence that Pfizer’s and Moderna’s vaccines are effective and safe for frail, vulnerable seniors in long-term care. Vaccines were not tested in this population. Federal officials insist side effects will be carefully monitored.

Next in line likely would be essential workers who cannot work from home, such as police, firefighters, teachers and people employed in food processing and transportation, according to commission deliberations Nov. 23 that have not come to a formal vote.

Then would be adults with high-risk medical conditions such as diabetes, cancer, kidney disease, obesity, heart disease and autoimmune diseases and all adults age 65 and older.

Although states typically follow ACIP guidelines, some states may choose, for instance, to vaccinate high-risk older adults before some categories of essential workers.

Left off the list are family caregivers, who provide essential support to vulnerable older adults living in the community — an unpaid workforce of tens of millions of people. “If someone is providing day-to-day care, it makes sense they should have access to the vaccine, too, to keep everyone safe,” said Beth Kallmyer, vice president of care and support for the Alzheimer’s Association.

Priority Groups

The priority groups constitute nearly half of the U.S. population — 21 million health care workers, 3 million long-term care residents, 66 million essential workers, more than 100 million adults with high-risk conditions and 53 million adults age 65 and older.

With initial supplies of vaccines limited, setting priorities will be inevitable. Practically, this means that hospitals and physicians may try to identify older adults who are at the highest risk of becoming seriously ill from COVID-19 and offer them vaccines before other seniors.

A study of more than 500,000 Medicare beneficiaries age 65 and older provides new evidence that could influence these assessments. It found the conditions that most increase older adults’ chances of dying from COVID-19 are sickle cell disease, chronic kidney disease, leukemias and lymphomas, heart failure, diabetes, cerebral palsy, obesity, lung cancer and heart attacks, in that order.

“Out of all Medicare beneficiaries, we identified just under 2,500 who had no medical problems and died of COVID-19,” said Dr. Martin Makary, co-author of the study and a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health in Baltimore. “We knew risk was skewed toward comorbidity [multiple underlying medical conditions], but we didn’t realize it skewed this much.”

Supplies Available

Both the Pfizer and Moderna vaccines require two doses, administered three to four weeks apart. The companies have said about 40 million doses of their vaccines should be available this year, enough to fully vaccinate about 20 million people.

After that, 50 million doses might become available in January, followed by 60 million doses in both February and March, according to Dr. Larry Corey, a virologist who heads the COVID-19 Prevention Trials Network.

That translates into enough vaccine for another 85 million people and should be sufficient to vaccinate older adults in addition to medical personnel on the front lines and many other at-risk individuals, Corey suggested at a recent panel on COVID-19 sponsored by the National Academy of Medicine and American Public Health Association.

He acknowledged these were estimates, based on information he has been given. Pfizer and Moderna have not yet specified how much vaccine will be delivered and when. Nor is it clear when other vaccines under investigation will become available — 13 are in phase 3 clinical trials — or what their monthly production capacity might be.

Distribution Issues

As Pfizer’s and Moderna’s vaccines are rolled out, a very vulnerable group may have difficulty getting them: 2 million seniors who are homebound and another 5.3 million with physical impairments who have problems getting around.

The reason: handling and cold storage requirements.

Pfizer’s vaccine needs to be stored at minus 70 degrees Celsius, calling for special equipment not available in small hospitals, clinics or doctors’ offices. Moderna’s vaccine needs long-term storage at minus 20 degrees Celsius.

Landmark Health provides in-home medical care to more than 120,000 frail, chronically ill homebound seniors in 15 states. “We don’t have the capabilities to store and distribute these vaccines to our population,” said Dr. Michael Le, the company’s co-founder and chief medical officer.

Instead, he said, Landmark is working to arrange transportation for its patients to centers where COVID-19 vaccines will be administered and educating them about the benefits of the vaccines. “Given the trust, the bond we have with our patients, we can play a big role as advocates,” Le said.

Addressing Mistrust

Advocates have a big job ahead of them. According to a recent poll from the University of Michigan, only 58% of older adults (ages 50 to 80) said they were very or somewhat likely to get a COVID-19 vaccine. A significant number of older adults, 46%, thought they’d get the vaccine eventually but wanted others to go first. Only 20% wanted to get it as soon as possible.

Most important in making decisions is knowing how well the vaccine works, according to 80% of the 1,556 older adults surveyed. Just over half (52%) said a recommendation from their doctor would be influential.

Dr. Sharon Inouye, a geriatrician at Hebrew Senior Life in Boston and a professor of medicine at Harvard Medical School, is among the physicians impatiently awaiting the publication of data from Pfizer’s and Moderna’s phase 3 clinical trials.

Among the things she wants to know: How many older adults with chronic health conditions participated? How many participants were 75 and older? Did side effects differ for older adults?

“What I worry about most is the side effects,” she said. “We may not be able to know about serious but rare side effects until millions of people take them.”

But that’s a gamble she’s willing to take. Not only will Inouye get a vaccine, she just told her 91-year-old mother, who lives in assisted living, to say “yes” when one is offered.

“My whole family lives in fear that something will happen to her every day,” Inouye said. “Even though there’s a lot we still don’t know about these vaccines, it’s compelling that we protect people from this overwhelming illness.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

New Drug Relieves Back Pain, But Safety Issues Remain

By Pat Anson, PNN Editor

An experimental non-opioid pain reliever gives long-term relief for chronic low back pain, but questions remain about joint damage and other side effects from the drug, according to a large new study.

Tanezumab is a humanized monoclonal antibody that targets nerve growth factor (NGF), a protein in the blood that heightens pain sensitivity. Tanezumab binds to NGF and inhibits pain signals from reaching the brain.

In a Phase III study of over 1,800 patients with difficult-to-treat low back pain, participants given an injection of tanezumab once every two months had significantly more pain relief than those given tramadol or a placebo. The study was funded by Pfizer and Eli Lilly, which have spent nearly a decade jointly developing tanezumab as an alternative to opioid medication.

"This demonstration of efficacy is a major breakthrough in the global search to develop non-opioid treatments for chronic pain," said lead author John Markman, MD, director of the Translational Pain Research Program at the University of Rochester Medical Center. "There were also improvements in function linked to the reduction in pain severity."

But this “major breakthrough” is tainted by the fact that about 10% of patients given 10mg of tanezumab had joint pain or other side effects. Seven of them needed total joint replacement surgery. Patients who received 5mg injections of tanezumab had fewer side effects, but less relief from back pain.

NGF inhibitors have previously been linked to a rapidly progressive form of osteoarthritis. But researchers say other methods of treating back pain, such as opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and surgery, have their own safety risks.

"In the future, clinicians may have to weigh the different risks of lumbar fusion surgery, chronic opioid use, or NSAIDs against the unique risks of a rare but rapidly progressive form of joint problem associated with blocking nerve growth factor," said Markman. "I expect that that the tradeoffs between benefit and risk will be different for osteoarthritis than for chronic low back pain."

Tanezumab is currently under review by the Food and Drug Administration as a treatment for moderate-to-severe osteoarthritis (OA), with a decision expected late this year. In a 2019 study of osteoarthritis patients taking a 5mg dose of tanezumab, there was significant improvement in their pain and physical function. But about 6% experienced rapidly progressive osteoarthritis.

Pfizer and Eli Lilly are not currently pursuing tanezumab as a treatment for chronic low back pain (CLBP).  

“Pfizer and Lilly made the decision to prioritize OA based on an assessment of the totality of SC tanezumab data and an initial discussion with the FDA,” a Pfizer spokesman said in an email to PNN. “At this time, regulatory submissions are not planned for tanezumab in patients with moderate-to-severe CLBP. Additional data analyses, and potentially further clinical study, may be required to more fully characterize tanezumab in CLBP patients.”

The new study was published in the journal Pain. Some of its findings had previously been released by Pfizer and Lilly.

FDA Reviewing New Osteoarthritis Drug

By Pat Anson, PNN Editor

A decade long effort to bring a new non-opioid pain reliever on the market is a step closer to reality – although lingering questions remain over the safety of the drug.

Pfizer and Eli Lilly have announced that the U.S. Food and Drug Administration has accepted for review a Biologics License Application for tanezumab as a treatment of chronic pain due to moderate-to-severe osteoarthritis (OA). The FDA set December 2020 as a goal for making a decision on the application.

Tanezumab is a humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases in the body because of injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

"The FDA acceptance of the tanezumab application represents a significant milestone, and the breadth of our regulatory submission reflects the extensive clinical data we have gathered for tanezumab over the course of its development," Ken Verburg, Pfizer’s tanezumab development team leader, said in a statement.

"There is an urgent need for innovation in the treatment of osteoarthritis, as there have been no new classes of medicines available for this debilitating condition in more than a decade. If approved, tanezumab would be a first-in-class treatment for patients suffering from chronic pain due to moderate-to-severe osteoarthritis who have experienced inadequate pain relief with other analgesics."

Pfizer and Eli Lilly are jointly developing tanezumab, which was given “fast track” designation by the FDA in 2017 to help speed its development. The companies submitted data to the FDA from 39 clinical studies evaluating the safety and efficacy of tanezumab on more than 18,000 patients.

A Phase 3 clinical study in 2018 found that osteoarthritis patients who were given two injections of tanezumab had significant improvement in their pain and physical function compared to a placebo.

Not all of the studies have been positive, however. Another Phase 3 study last year found that over 6% of osteoarthritis patients taking a 5 mg dose of tanezumab experienced rapidly progressive OA in their joints. There was significant improvement in their pain and physical function, but the patients’ overall assessment of their condition was no better than those treated with non-steroidal anti-inflammatory drugs (NSAIDs).

Patients in the same study taking a lower 2.5 mg dose of tanezumab did not have any significant improvement in their pain, quality of life or overall condition. And 3.2% experienced rapidly progressive osteoarthritis. The license application accepted by the FDA is for that smaller 2.5 mg dose.

In 2010, Pfizer reported some osteoarthritis patients taking tanezumab experienced worsening of their disease and needed joint replacements. Another safety issue arose in 2012 because the drug caused “adverse changes in the sympathetic nervous system of mature animals.”

There is some concern that NGF antibodies work too well and encourage osteoarthritis patients to become more active, which accelerates joint deterioration. More than 27 million Americans live with osteoarthritis, 11 million of whom have moderate-to-severe OA.

Tanezumab is also being evaluated as a treatment for cancer pain due to bone metastases in a Phase 3 study. At one time, it was studied as a possible treatment for low back pain, but Pfizer and Eli Lilly are now mainly focused on tanezumab as a treatment for osteoarthritis.

Are You Paying Too Much for Pregabalin?

By Pat Anson, PNN Editor

It didn’t take long for cheaper generic versions of pregabalin to take a bite out of Pfizer’s monopoly of Lyrica, a drug widely used to treat fibromyalgia, diabetic neuropathy and other types of chronic pain.

Last month the U.S. Food and Drug Administration gave approval to rival drug makers to begin selling generic pregabalin after Pfizer’s patent on Lyrica expired. According to FiercePharma, Pfizer lost about a third of the market for pregabalin to 16 competitors by the end of July.  

It’s not hard to see why. According to Healthcare Bluebook, a 60-day supply of 75mg Lyrica sells for a “fair price” of $472. That compares to generic versions that sell for about $28.

“The price that most patients pay is set by insurers. The cost difference for patients between brand-name Lyrica and generic pregabalin may vary depending on the patients’ insurance plan, the state in which their prescription is filled, or the pharmacy where they pick up their prescription,” said Steven Danehy, a Pfizer spokesman.

As of August 9, Lyrica still had about 43% of the market for pregabalin, but that’s likely to change as patients, doctors and insurers became more aware of the significant difference in price.

Pregabalin is approved by the FDA for the treatment of pain associated with shingles, spinal cord injury, fibromyalgia, and diabetic peripheral neuropathy. It is also commonly prescribed "off label" for other types of chronic pain.

Pregabalin is a Schedule V controlled substance, which means it has a low potential for abuse. In recent years, however, there is growing concern that pregabalin and its sister drug gabapentin (Neurontin) are being abused and overprescribed.

The drugs, which belong to a class of nerve medication called gabapentinoids, were originally developed to treat epilepsy, not pain. Prescriptions for gabapentinoids have tripled over the past 15 years as more doctors prescribed them as “safer” alternatives to opioids.

Deaths involving gabapentinoids have increased in the UK, Australia and Canada, where some addicts have learned the drugs can heighten the euphoric effect of heroin and other opioids. The drugs were recently classified as controlled substances in the UK.

CreakyJoints Under Scrutiny for Ties to Drug Makers

By Pat Anson, PNN Editor

Patient advocacy groups are coming under scrutiny again for their financial ties to drug companies. The latest is the Global Healthy Living Foundation (GHLF), a non-profit charity that created CreakyJoints, a website and social media platform that raises awareness about arthritis and other chronic illnesses. 

According to Bloomberg News reporter Ben Elgin, the foundation and CreakyJoints have long had a cozy relationship with Pfizer, Amgen, Johnson & Johnson and other corporate donors. Pfizer has donated nearly $1 million to the foundation over the past decade and one of its vice-presidents even serves on GHLF’s board of directors.

In a speech to drug makers in 2010, GHLF president Seth Ginsberg reportedly sought their donations -- while at the same time promising the companies “higher profits” and “sales rep participation in our programs.”

Ginsberg, who was diagnosed with spondyloarthritis as a teenager, co-founded GHLF in 1999 with marketing executive Louis Tharp.

In addition to CreakyJoints, GHLF has two other “grassroots” programs, Fail First Hurts and the 50-State Network, which advocate for healthcare policies that often align with the interests of its donors.  

According to GHLF’s 2017 tax return, the foundation had over $5 million in annual revenue. Ginsberg was paid a salary of $384,000, while Tharp received $220,000 as Executive Director.  Nearly $300,000 was also paid to a for-profit marketing company established by the two men, although it’s unclear what the payment was for.

Bloomberg reported that GHLF’s tax returns “reflect errors and unexplained entries that have obscured the amounts of money flowing to its cofounders.”

“Are they operating in a way that is extremely transparent? It’s safe to say they’re not,” Brian Mittendorf, a professor of accounting at Ohio State University told Bloomberg. “From looking at their disclosures, you have no idea how closely they’re related to some of the entities it pays.”

At least one GHLF board member and several patient volunteers reportedly left the organization because they were troubled by its relationships with donors.

GHLF did not grant an interview to Bloomberg, but replied to questions in writing.

“The only time we engage in advocacy is when it helps patients. If it doesn’t help patients, we don’t do it,” the foundation said in a statement. “Our mission is to engage in patient-centered research, provide advocacy for access-to-care, and to support people living with chronic disease by providing a supportive environment and accessible education.”

In a related story, Bloomberg reported that several other recently formed non-profits – such as the U.S. Rural Health Network --  appear to be little more than front organizations for the pharmaceutical industry.

“There are a number of groups created by pharma companies that look and act like patient organizations, but they’re 100 percent funded by industry,” said Marc Boutin, chief executive officer of the National Health Council. “They sound and look like patient organizations, but they take positions that industry wants.”

Drug Companies Fined for Co-Pay Programs

Last week two drug companies agreed to pay $125 million in fines to settle allegations that they used charitable foundations as front organizations to bilk Medicare.

Amgen and Japanese drug maker Astellas Pharma paid the foundations to establish co-pay prescription drug programs for Medicare patients. Federal prosecutors say the programs were primarily designed not to help patients, but to illegally pay their co-pays for Astellas and Amgen products.

Federal anti-kickback laws prohibit pharmaceutical companies from making any kind of payment to induce Medicare patients to purchase their drugs. The prohibition includes co-pays.

“The companies’ payments to the foundations were not ‘donations,’ but rather were kickbacks that undermined the structure of the Medicare program and illegally subsidized the high costs of the companies’ drugs at the expense of American taxpayers,” U.S. Attorney Andrew Lelling said in a statement.

“When pharmaceutical companies use foundations to create funds that are used improperly to subsidize the co-pays of only their own drugs, it violates the law and undercuts a key safeguard against rising drug costs,” said U.S. Assistant Attorney General Jody Hunt.

Last year, Pfizer paid nearly $24 million to settle allegations that it also used a co-pay program to pay Medicare for the company’s prescription drugs.

U.S. Pain Foundation Co-Pay

The U.S. Pain Foundation is under investigation by the U.S. Senate Finance Committee for a similar co-pay program established with Insys Therapeutics, a controversial Arizona drug company. Insys makes Subsys, an expensive and potent fentanyl spray blamed for hundreds of overdose deaths.

U.S. Pain received $2.5 million from Insys to launch the “Gain Against Pain” program, which ostensibly helped Medicare patients pay for drugs prescribed for breakthrough cancer pain. Critics say the program was primarily used to increase prescriptions for Subsys, which can cost $24,000 for just a four-day supply.

Former U.S. Pain CEO Paul Gileno initially defended the co-pay program, saying the money from Insys “does not influence our values,” but later resigned over allegations that he misappropriated $2 million from his own charity.

The Gain Against Pain program was subsequently shutdown in August 2018 and U.S. Pain said it would no longer accept funding from Insys.

Sen. Ron Wyden (D-OR), the ranking member of the Senate Finance Committee, sent a lengthy letter last December to U.S. Pain interim CEO Nicole Hemmenway asking a series of questions about the Insys co-pay program. According to the senator’s office, Wyden has still not gotten a full response.  

“The U.S. Pain Foundation has yet to provide a substantial amount of the information that Senator Wyden requested in his letter. Staff is in communication with the organization in order to get to the bottom of the organization’s financial relationship with pharmaceutical manufacturers, including Insys, and its compliance with applicable federal laws,” a Wyden spokesperson said in a statement to PNN.

A federal jury in Boston is currently in its third week of deliberations in a criminal case against Insys founder John Kapoor and four former executives of the company, who are accused of bribing doctors to boost sales of Subsys. 

U.S. Pain also remains under investigation by the Connecticut Attorney General’s office for financial irregularities that led to Gileno’s resignation.