Will FDA’s New Review Process Sell Drug Approvals to the Highest Bidder?

By Crystal Lindell

The U.S. Food and Drug Administration has launched a new speedy review process for new medications, dubbed the Commissioner’s National Priority Voucher (CNPV) program. 

The FDA claims the program will speed up the approval process for pharmaceutical companies looking to get a new drug on the market – but it remains unclear whether it is based on a need for the drug, its effectiveness, or how much companies are willing to pay for the privilege of early approval..

The FDA said the CNPV program will shorten the review time to 1-2 months, compared to the typical 10-12 months it usually takes after a company’s final drug application.

They’ll accomplish this by allowing for a “team-based review.” This differs from the current process, where a drug application is “sent to numerous FDA offices” to give them a chance to weigh-in.

The program will even allow companies to submit the lion’s share of the drug application before a clinical trial is complete, according to FDA Commissioner Marty Makary, MD.

“Using a common-sense approach, the national priority review program will allow companies to submit the lion’s share of the drug application before a clinical trial is complete so that we can reduce inefficiencies. The ultimate goal is to bring more cures and meaningful treatments to the American public,” Makary said. 

Neither the FDA press release about the new program or its "Frequently Asked Questions" page specify how much this new program will cost companies interested in participating. 

We can gain some frame of reference by looking at what the existing Priority Review and Priority Review Voucher costs for companies, as well as what their true value is. 

While the FDA charges companies about $2.5 million for those vouchers, according to the General Accounting Office (GAO) they have been resold on the secondary market for as much as $350 million. The GAO found that of the 31 vouchers awarded by the FDA between 2009 and 2019, over half (17) were sold to another drug company.

The new vouchers cannot be transferred to other companies as of now, but with so much money at stake, you have to wonder if there will be a valuable aftermarket for them.

Even if the new vouchers themselves are reasonably priced, my guess is that they will be more likely to go to companies that donate money to elected officials or are politically favored. 

The FDA says that in the first year of the program it will give a limited number of vouchers to companies “aligned with U.S. national priorities,” which include “unmet public health needs” and increased domestic drug manufacturing. But then they also say the vouchers “can be applied to drugs in any area of medicine.”

In other words, basically any medication would qualify. There’s not much else to explain just how vague the criteria is for receiving the vouchers.  

And if any medication would qualify for the new vouchers, it makes sense that the ultimate qualification would be what companies are willing to pay to get them. 

Under the current voucher system, the GAO found there is “no obligation to make the approved drug available at an affordable price,” so companies are free to limit access and charge whatever they want. The new voucher system also has no requirement that new drugs will be affordable or accessible. 

While I do understand the need for more efficiencies in the drug review process, when those efficiencies are applied unevenly, it inevitably invites corruption. And the last thing we need when it comes to prescription medications and healthcare in our country is more corruption. 

My concern is that the drugs getting speedy review won’t actually be the ones that are in the public’s best interests, but rather the ones that best serve the interests of our elected officials and the drug companies themselves. 

And when it comes to prescription medications, we all know that what’s best for politicians and the pharmaceutical industry is not what’s best for patients.

Former CDC Commissioner: Kratom Has ‘Low Abuse Potential’

By Pat Anson

The U.S. Food and Drug Administration has a conflicted and contentious history with kratom, the herbal supplement used by millions of Americans to self-treat their pain, anxiety, and depression.  

Kratom has been used for centuries in southeast Asia as a natural stimulant and pain reliever, but only in the past decade has it become widely available in the United States -- over the strong objections of the FDA.

In 2016, the FDA joined with the DEA in proposing that kratom be classified as an illegal Schedule I controlled substance due to its abuse potential, a request that was later withdrawn due to a public outcry.

That setback didn’t stop then-FDA Commissioner Scott Gottlieb, MD, from launching a public relations campaign demonizing and mischaracterizing kratom as an addictive “opioid.” Gottlieb cited FDA research that an Assistant Secretary for Health later called “embarrassingly poor evidence & data.”

To improved its data, last year the FDA said it would conduct a new study on the risks and safety of kratom, and then abruptly cancelled it without explanation, claiming kratom has a “chemical affinity” with opioids and should not be used to treat medical conditions. “The use of this substance, that has yet to be tested and determined safe for use in human population by the Agency, is a significant concern,” the FDA said.

The claim that kratom “has yet to be tested and determined safe” is misleading, because the FDA had just completed a pilot study showing that kratom is relatively safe, even at doses as high as 12 grams -- the equivalent of taking 24 capsules of kratom leaf powder within five minutes.   

“In 2024, the FDA completed a single ascending-dose clinical trial examining ground kratom leaf in experienced users. The results were illuminating: participants experienced no serious adverse events at doses up to 12 grams, with side effects limited to mild nausea and pupil constriction. Crucially, subjective ‘drug liking’ scores never reached statistical significance compared to placebo, indicating low abuse potential for natural leaf,” former CDC Commissioner Robert Redfield, MD, said in an op/ed published today in The Hill.

Redfield’s comment is notable, because the FDA itself has never had much to say about its 2024 study and still hasn’t posted the final results. According to the American Kratom Association, FDA researchers were "profoundly disappointed” at the lack of adverse events associated with kratom, as that doesn’t square with the agency’s long-held public position on kratom.

Redfield may be reassured of the safety of natural kratom, but he thinks the federal government should take emergency action to ban the import and sale of synthetic kratom extracts, which have elevated levels of 7-hydroxymitragynine, an alkaloiid that is present in only minute amounts in the natural leaf. Kratom extracts have been associated with serious adverse events and overdoses.  

Redfield says synthetic kratom has “pharmaceutical-grade opioid chemistry” and should be taken off the market immediately. But he thinks natural kratom is relatively safe, and cites the 2024 study as evidence.

“This clinical evidence establishes a critical scientific baseline: natural kratom leaf, when used as it has been for centuries, presents a markedly different risk profile than the synthetic products flooding American markets,” Redfield wrote. “This is not about banning kratom. Full spectrum kratom, used responsibly, appears to have acceptable safety margins based on FDA’s own clinical data. This is about preventing synthetic opioids from hiding behind botanical names.”

The FDA still has “serious safety concerns” about natural kratom, but has little evidence to back them up and is apparently slow-walking research. Only two federally-funded kratom studies are currently recruiting participants. One would study the effects of natural kratom and the potential for withdrawal, while the second trial would study the effects of kratom extracts.

Both studies are small and won’t be completed until 2028 —- over a decade after the agency tried to get kratom banned nationwide.

Meloxicam Almost Killed My Mom, Now FDA Has Approved an IV Version

By Crystal Lindell

Buried in the fine print for the newest non-opioid pain medication to be approved by the FDA is a stark warning that hits close to home. 

The FDA just approved Xifyrm, which is the branded IV version of the non-steroidal anti-inflammatory drug meloxicam for adults with moderate-to-severe pain.

It offers once daily dosing, and of course, manufacturer Azurity Pharmaceuticals highlights the fact that "Xifyrm provides a non-opioid analgesic" in its press release about the drug. 

There’s just one problem: it’s the same drug that almost killed my mom in 2022. 

If you look at the fine print in the prescribing information, you’ll see the disclaimer that points to one of the major risks that come with this medication. 

"NSAIDs, including meloxicam, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal,” Azurity warns.

They go on to say that these serious adverse events “can occur at any time, with or without warning symptoms.”

And 4 out 5 patients who develop these complications have no warning signs at all. 

Azurity then shares how common these complications are, writing that they occur in “1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year.”

They also add that “even short-term NSAID therapy is not without risk.”

Unfortunately, my mom was in the group of 2-4% of patients who were treated with mexlicam for one year and then had serious complications. 

Her doctor gave her the oral version for chronic hip pain because he didn’t want to give her opioids. She took it exactly as prescribed, and about one year later, meloxicam almost killed her. 

She had a very sudden and very serious perforated ulcer. 

My mom had no warning symptoms, just as the fine print for Xifyrm warns can happen. She collapsed at work and then was taken to the emergency room via ambulance. There, her sudden intense stomach pain was dismissed by staff for 9 hours before she finally got a CT scan. She was then immediately rushed into emergency surgery for a perforated ulcer. 

My mom spent the next week in critical care, unable to eat or drink anything at all for a full week while her stomach healed. 

It was a harrowing experience made worse by the fact that all of this happened during the height of the COVID lockdown, meaning none of us were able to visit her at all while she was in the hospital. 

And the thing is, she is one of the lucky ones, because she survived. 

We often hear harrowing tales of opioids causing overdose deaths, but that doesn’t mean that alternatives like NSAIDs are safe. The fact that 2-4% of patients could have a potentially fatal complication from this drug should scare both doctors and patients. 

Many doctors hesitate to prescribe opioid pain medications these days, even for post-surgical and cancer pain, and my fear is that this new IV version of meloxicam will quickly become one of their favorite alternatives, just as the oral version already is. 

Interestingly, the FDA recently released a boxed warning for veterinarians on the use of meloxicam in cats before surgery, saying repeated off-label use can cause sudden kidney failure and even death. 

When it comes to humans, it’s also noteworthy that Azuirty also makes it clear that this new IV medication shouldn’t be used alone when rapid pain relief is needed. That allows for the potential use of opioids, but I’m skeptical that doctors will heed that advice. 

A lot of doctors have an “avoid opioids at all costs” approach to pain care these days, but many of them have not reckoned with what that can actually mean for patients. They also rarely go over the true risks of NSAIDs with their patients, despite the fact that lectures about the dangers of opioids are common in medical care. 

These days, my mom is in good health, and in fact we just celebrated her 64th birthday. It’s a milestone that’s now all the more precious after we almost lost her.

I would urge doctors to exercise extreme caution when turning to opioid alternatives like Xifyrm, and other NSAIDs. They are not without risk. And in fact, they can be more dangerous than opioids. 

FDA Warns Again About ‘Gas Station Heroin’

By Pat Anson

The Food and Drug Administration is once again warning Americans about the harmful effects of tianeptine, an antidepressant found in supplements sold online and in convenience stores to help with energy, mood, pain and sexual performance.

Tianeptine is essentially an unregulated drug in the United States. It is not currently scheduled under the Controlled Substances Act, but is also not approved by the FDA for any medical use. It is, however, approved in low doses as a treatment for depression and anxiety in several European, Asian and Latin American counties.

The problem in the U.S. is that tianeptine is being sold in supplements without a prescription at doses up to 250 times higher than what is typically recommended in foreign drug products. At high doses, tianeptine can cause confusion, agitation and euphoria – which has led some to call it “gas station heroin.”

“I am very concerned. I want the public to be especially aware of this dangerous product and the serious and continuing risk it poses to America’s youth,” FDA Commissioner Dr. Martin Makary said in a “Dear Colleagues” letter to healthcare professionals.

“While the FDA is closely following the distribution and sale of these products, it is critical that you appreciate the magnitude of the underlying danger of these products, and disseminate information about it.”

This isn’t the first time the FDA has warned about tianeptine. In 2023, the agency warned consumers not to purchase or consume tianeptine products sold under the brand name Neptune’s Fix, which it blamed for “severe adverse events” such as seizures and loss of consciousness. A few months later, the FDA sent a warning letter to retailers telling them to stop selling Neptune’s Fix and any other products containing tianeptine.

Makary’s letter does not make clear why another warning about tianeptine is needed. It implies the drug is increasingly used by young people, but provides no statistics or examples of it harming users.

Since 2023, the FDA’s Adverse Events Reporting System has recorded less than a hundred cases of adverse health events involving tianeptine, most of them involving “persistent genital arousal disorder.”

Like other antidepressants, tianeptine can be used to relieve pain. A 2023 study on laboratory mice found tianeptine to be a fast-acting pain reliever, with low risk of addiction.

“We hope this revives the potential of using tianeptine for the treatment of chronic pain and associated conditions, such as anxiety and depression,” said lead author Venetia Zachariou, PhD, Chair of Pharmacology at Boston University’s School of Medicine. “By further refining this molecule, we could arrive at a pain treatment that is more effective, fast acting, and has a mild side effect profile.”

Other studies have show tianeptine may be effective as a treatment for asthma, irritable bowel syndrome, fibromyalgia, and ADHD. Like any drug, however, tianeptine can be harmful when its abused, taken in high doses, or combined with other drugs.

“Tianeptine is often taken recreationally, but it has also been used to self-treat a variety of ailments. It is frequently used chronically and, if stopped abruptly, users may experience withdrawal symptoms,” Makary said in his letter. “Historically, there has been a delayed recognition of fast-growing trends, such as opioid abuse and vaping addiction in youth. Let’s be proactive in understanding and addressing the use of tianeptine products.”

Experimental Cannabis Extract Has ‘Potential to Replace Opiates’

By Pat Anson

A German biotech company says it is seeking regulatory approval in Europe and the United States for an experimental cannabis extract that could be an alternative to opioid pain medication.

Vertanical recently completed two Phase 3 studies of its new drug – called VER-01 – on over 1,000 patients with chronic low back pain who didn’t get sufficient relief from non-opioid analgesics.

One study compared VER-01 to a placebo, while the second trial compared the drug’s safety and tolerability to patients treated with opioids. The company told The Times it was awaiting publication of the studies’ findings in The Lancet before making them public.

“VER-01 reduces pain without creating dependency or having an abuse potential,” said Clemens Fischer, MD, Vertanical’s CEO. “It has the full potential to replace opiates as it’s more effective. It’s a real alternative for chronic patients — the first one.

“Pain patients around the world are trapped in a vicious cycle of pain, insomnia, limited mobility, and depression. VER-01 has the potential to successfully break this cycle.”

VER-01 is a “full-spectrum” extract derived from cannabis sativa leaves and flowers. Although it contains THC, the main psychoactive substance in cannabis, Fischer says patients enrolled in the studies didn’t become high or intoxicated. About 25 percent did “feel a bit dizzy” for two weeks after they started taking it.

Participants also didn’t get “the munchies” or gain weight, a well-known side effect of cannabis.

“We were looking very carefully, because that’s what we hear from cannabis smokers — that the appetite increases as well their weight. But we haven’t seen any increase in weight,” Fischer told The Times.

Vertanical is seeking regulatory approval of VER-01 in Europe and with the UK’s Medicines and Healthcare Products Regulatory Agency. If granted, VER-01 would be the first cannabis-based medicine approved for chronic pain. It would be sold under the brand name Exilby and be taken orally in drops.

The timeline for approval in Europe may be as soon as this summer, but it’s likely to take longer in the U.S.

“We are seeking regulatory approval in the US and are in talks with the FDA. For approval in the US, a further phase 3 study with US patients in the indication of chronic low back pain will start in Q2 2025,” Merit Renner, Senior Manager of Business Development at Vertanical, told PNN in an email. “This, together with the phase 3 study successfully conducted in Europe, will form the basis for approval in the US.”

Vertanical also plans further studies of VER-01 on patients with osteoarthritis and peripheral neuropathy.

Research into the pain-relieving properties of cannabis has been slow in the U.S., in large part because of marijuana’s status as a Schedule 1 Controlled Substance, the same classification as LSD and heroin. The DEA recently allowed more marijuana to be used for research purposes, but has dragged its feet about reclassifying marijuana as a Schedule 3 substance that could be used for medical purposes. Until marijuana is rescheduled, VER-01 is unlikely to get FDA approval.

Some recent studies have shown that certain cannabinoids found in marijuana -- cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) – block pain signals in the peripheral nervous system, not the brain, and don’t have a psychoactive effect that could lead to abuse.

“These findings open new avenues for the development of cannabinoid-based therapies,” said Mohammad-Reza Ghovanloo, PhD, lead author of a study published in PNAS and a research scientist at Yale School of Medicine. “Our results show that CBG in particular has the strongest potential to provide effective pain relief without the risks associated with traditional treatments.”

The cannabinoids in the Yale study interact with a protein in cell membranes called Nav1.8, which blocks peripheral nerves from transmitting pain signals. Inhibiting Nav1.8 is the same method used by Journavx (suzetrigine), a non-opioid analgesic recently approved by the FDA for relieving moderate to severe acute pain in adults.

FDA Approves New Non-Opioid Pain Reliever

By Pat Anson

Despite lackluster results in clinical trials, the U.S. Food and Drug Administration has approved a new non-opioid pain reliever for moderate to severe acute pain in adults.

Journavx (suzetrigine) is the first new medication for acute, short-term pain in over two decades. Unlike opioids, Journavx blocks pain signals in the peripheral nervous system, not in the brain, so it doesn’t have the same “liking” effects of opioids, which can lead to dependence or addiction.

The FDA calls its approval “an important public health milestone.”

"A new non-opioid analgesic therapeutic class for acute pain offers an opportunity to mitigate certain risks associated with using an opioid for pain and provides patients with another treatment option. This action and the agency's designations to expedite the drug's development and review underscore FDA's commitment to approving safe and effective alternatives to opioids for pain management," said Jacqueline Corrigan-Curay, MD, acting director of the FDA's Center for Drug Evaluation and Research.

Journavx was developed by Vertex Pharmaceuticals, which anticipates the drug to be used primarily for relieving post-operative pain or trauma. It is also being studied as a treatment for diabetic peripheral neuropathy and other types of chronic pain.

“This is an incredible day for patients and physicians alike who now have an approved non-opioid treatment that delivers effective acute pain relief and a favorable safety profile without addictive potential,” said Jessica Oswald, MD, a Vertex consultant and Associate Physician in Emergency Medicine and Pain Medicine in San Diego.

“I believe Journavx could redefine the management of pain and become a foundational treatment option for people with all types of moderate-to-severe acute pain, where options aside from opioids have been so desperately needed.”

VERTEX IMAGE

The results from clinical trials suggest that Journavx is a mild pain reliever, at best.

In Phase 3 clinical studies of acute pain after minimally invasive surgeries, Journavx was no more effective than a low-dose combination of hydrocodone and acetaminophen, more commonly known as Vicodin.

In a recent Phase 2 study, Journavx was essentially no better than a placebo in relieving chronic back and hip pain caused by lumbosacral radiculopathy.

A recent report by ICER, an independent, non-profit research institute, said there were “uncertainties” about the efficacy and safety of Journavx.

“We have concerns about as-yet-unknown harms of suzetrigine as we would for any drug with a new mechanism of action; we are particularly concerned about whether there could be an increased risk for cardiac arrhythmias… and possible acute renal injury given a study in people with diabetes,” ICER said. “The above uncertainties inform our ratings that the evidence for suzetrigine for the treatment of acute pain in comparison with no systemic treatment, in comparison with opioid analgesics, and in comparison with NSAIDs are all promising but inconclusive.”

Journavx is being priced by Vertex at a wholesale cost for $15.50 per 50mg pill. When taken twice a day for acute pain, ICER estimates the cost at $420 for a one-week course. By comparison, a supply of 100 Vicodin tablets costs about $142.

The FDA’s approval of Journavx coincides with implementation of the NOPAIN Act, which makes non-opioid analgesics in outpatient surgical settings eligible for higher Medicare reimbursement rates.  

The risk of a surgery patient misusing opioids or becoming addicted is less than one percent. One study found that patients who received no opioids during surgery were more likely to have post-operative pain and require opioids during recovery.

Long Covid Patients Frustrated by Lack of New Treatments

By Sarah Boden, KFF Health News

Erica Hayes, 40, has not felt healthy since November 2020 when she first fell ill with covid.

Hayes is too sick to work, so she has spent much of the last four years sitting on her beige couch, often curled up under an electric blanket.

“My blood flow now sucks, so my hands and my feet are freezing. Even if I’m sweating, my toes are cold,” said Hayes, who lives in Western Pennsylvania. She misses feeling well enough to play with her 9-year-old son or attend her 17-year-old son’s baseball games.

Along with claiming the lives of 1.2 million Americans, the covid-19 pandemic has been described as a mass disabling event. Hayes is one of millions of Americans who suffer from long covid.

Depending on the patient, the condition can rob someone of energy, scramble the autonomic nervous system, or fog their memory, among many other symptoms.

In addition to the brain fog and chronic fatigue, Hayes’ constellation of symptoms includes frequent hives and migraines. Also, her tongue is constantly swollen and dry.

“I’ve had multiple doctors look at it and tell me they don’t know what’s going on,” Hayes said about her tongue. 

ERICA HAYES

Estimates of prevalence range considerably, depending on how researchers define long covid in a given study, but the Centers for Disease Control and Prevention puts it at 17 million adults.

Despite long covid’s vast reach, the federal government’s investment in researching the disease — to the tune of $1.15 billion as of December — has so far failed to bring any new treatments to market. 

This disappoints and angers the patient community, who say the National Institutes of Health should focus on ways to stop their suffering instead of simply trying to understand why they’re suffering.

“It’s unconscionable that more than four years since this began, we still don’t have one FDA-approved drug,” said Meighan Stone, executive director of the Long COVID Campaign, a patient-led advocacy organization. Stone was among several people with long covid who spoke at a workshop hosted by the NIH in September where patients, clinicians, and researchers discussed their priorities and frustrations around the agency’s approach to long-covid research.

Some doctors and researchers are also critical of the agency’s research initiative, called RECOVER, or Researching COVID to Enhance Recovery. Without clinical trials, physicians specializing in treating long covid must rely on hunches to guide their clinical decisions, said Ziyad Al-Aly, chief of research and development with the VA St Louis Healthcare System.

“What [RECOVER] lacks, really, is clarity of vision and clarity of purpose,” said Al-Aly, saying he agrees that the NIH has had enough time and money to produce more meaningful progress.

Now the NIH is starting to determine how to allocate an additional $662 million of funding for long-covid research, $300 million of which is earmarked for clinical trials. These funds will be allocated over the next four years. At the end of October, RECOVER issued a request for clinical trial ideas that look at potential therapies, including medications, saying its goal is “to work rapidly, collaboratively, and transparently to advance treatments for Long COVID.”

This turn suggests the NIH has begun to respond to patients. This has stirred cautious optimism among those who say that the agency’s approach to long covid has lacked urgency in the search for effective treatments. Stone calls this $300 million a down payment. She warns it’s going to take a lot more money to help people like Hayes regain some degree of health.“There really is a burden to make up this lost time now,” Stone said.

The NIH told KFF Health News and NPR via email that it recognizes the urgency in finding treatments. But to do that, there needs to be an understanding of the biological mechanisms that are making people sick, which is difficult to do with post-infectious conditions.

That’s why it has funded research into how long covid affects lung function, or trying to understand why only some people are afflicted with the condition.

Good Science Takes Time

In December 2020, Congress appropriated $1.15 billion for the NIH to launch RECOVER, raising hopes in the long-covid patient community.

Then-NIH Director Francis Collins explained that RECOVER’s goal was to better understand long covid as a disease and that clinical trials of potential treatments would come later.

According to RECOVER’s website, it has funded eight clinical trials to test the safety and effectiveness of an experimental treatment or intervention. Just one of those trials has published results.

On the other hand, RECOVER has supported more than 200 observational studies, such as research on how long covid affects pulmonary function and on which symptoms are most common. And the initiative has funded more than 40 pathobiology studies, which focus on the basic cellular and molecular mechanisms of long covid.

RECOVER’s website says this research has led to crucial insights on the risk factors for developing long covid and on understanding how the disease interacts with preexisting conditions. It notes that observational studies are important in helping scientists to design and launch evidence-based clinical trials.

Good science takes time, said Leora Horwitz, the co-principal investigator for the RECOVER-Adult Observational Cohort at New York University. And long covid is an “exceedingly complicated” illness that appears to affect nearly every organ system, she said. 

This makes it more difficult to study than many other diseases. Because long covid harms the body in so many ways, with widely variable symptoms, it’s harder to identify precise targets for treatment.

“I also will remind you that we’re only three, four years into this pandemic for most people,” Horwitz said. “We’ve been spending much more money than this, yearly, for 30, 40 years on other conditions.”

NYU received nearly $470 million of RECOVER funds in 2021, which the institution is using to spearhead the collection of data and biospecimens from up to 40,000 patients. Horwitz said nearly 30,000 are enrolled so far.

This vast repository, Horwitz said, supports ongoing observational research, allowing scientists to understand what is happening biologically to people who don’t recover after an initial infection — and that will help determine which clinical trials for treatments are worth undertaking.

“Simply trying treatments because they are available without any evidence about whether or why they may be effective reduces the likelihood of successful trials and may put patients at risk of harm,” she said.

‘I’m Just Disgusted’

The NIH told KFF Health News and NPR that patients and caregivers have been central to RECOVER from the beginning, “playing critical roles in designing studies and clinical trials, responding to surveys, serving on governance and publication groups, and guiding the initiative.” But the consensus from patient advocacy groups is that RECOVER should have done more to prioritize clinical trials from the outset. Patients also say RECOVER leadership ignored their priorities and experiences when determining which studies to fund.

RECOVER has scored some gains, said JD Davids, co-director of Long COVID Justice. This includes findings on differences in long covid between adults and kids. But Davids said the NIH shouldn’t have named the initiative “RECOVER,” since it wasn’t designed as a streamlined effort to develop treatments.

“The name’s a little cruel and misleading,” he said.

RECOVER’s initial allocation of $1.15 billion probably wasn’t enough to develop a new medication to treat long covid, said Ezekiel J. Emanuel, co-director of the University of Pennsylvania’s Healthcare Transformation Institute.

But, he said, the results of preliminary clinical trials could have spurred pharmaceutical companies to fund more studies on drug development and test how existing drugs influence a patient’s immune response.

Emanuel is one of the authors of a March 2022 covid roadmap report. He notes that RECOVER’s lack of focus on new treatments was a problem. “Only 15% of the budget is for clinical studies. That is a failure in itself — a failure of having the right priorities,” he told KFF Health News and NPR via email.

And though the NYU biobank has been impactful, Emanuel said there needs to be more focus on how existing drugs influence immune response.

He said some clinical trials that RECOVER has funded are “ridiculous,” because they’ve focused on symptom amelioration, for example to study the benefits of over-the-counter medication to improve sleep. Other studies looked at non-pharmacological interventions, such as exercise and “brain training” to help with cognitive fog.

People with long covid say this type of clinical research contributes to what many describe as the “gaslighting” they experience from doctors, who sometimes blame a patient’s symptoms on anxiety or depression, rather than acknowledging long covid as a real illness with a physiological basis.

“I’m just disgusted,” said long-covid patient Hayes. “You wouldn’t tell somebody with diabetes to breathe through it.”

Chimére L. Sweeney, director and founder of the Black Long Covid Experience, said she’s even taken breaks from seeking treatment after getting fed up with being told that her symptoms were due to her diet or mental health.

“You’re at the whim of somebody who may not even understand the spectrum of long covid,” Sweeney said.

Insurance Battles Over Experimental Treatments

Since there are still no long-covid treatments approved by the Food and Drug Administration, anything a physician prescribes is classified as either experimental — for unproven treatments — or an off-label use of a drug approved for other conditions. This means patients can struggle to get insurance to cover prescriptions.

Michael Brode, medical director for UT Health Austin’s Post-COVID-19 Program — said he writes many appeal letters. And some people pay for their own treatment.

For example, intravenous immunoglobulin therapy, low-dose naltrexone, and hyperbaric oxygen therapy are all promising treatments, he said.

For hyperbaric oxygen, two small, randomized controlled studies show improvements for the chronic fatigue and brain fog that often plague long-covid patients. The theory is that higher oxygen concentration and increased air pressure can help heal tissues that were damaged during a covid infection.

However, the out-of-pocket cost for a series of sessions in a hyperbaric chamber can run as much as $8,000, Brode said.

“Am I going to look a patient in the eye and say, ‘You need to spend that money for an unproven treatment’?” he said. “I don’t want to hype up a treatment that is still experimental. But I also don’t want to hide it.”

There’s a host of pharmaceuticals that have promising off-label uses for long covid, said microbiologist Amy Proal, president and chief scientific officer at the Massachusetts-based PolyBio Research Foundation. For instance, she’s collaborating on a clinical study that repurposes two HIV drugs to treat long covid.

Proal said research on treatments can move forward based on what’s already understood about the disease. For instance, she said that scientists have evidence — partly due to RECOVER research — that some patients continue to harbor small amounts of viral material after a covid infection. She has not received RECOVER funds but is researching antivirals.

But to vet a range of possible treatments for the millions suffering now — and to develop new drugs specifically targeting long covid — clinical trials are needed. And that requires money.

Hayes said she would definitely volunteer for an experimental drug trial. For now, though, “in order to not be absolutely miserable,” she said she focuses on what she can do, like having dinner with her family. At the same time, Hayes doesn’t want to spend the rest of her life on a beige couch. 

RECOVER’s deadline to submit research proposals for potential long-covid treatments is Feb. 1.

(Update: The Trump administration recently ordered an “immediate pause” on all communications, reports, scientific meetings, and funding reviews by federal health agencies. It’s not clear how long the order will last or affect long covid research.)

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

FDA Approved Genetic Test for Opioid Use Disorder Is Flawed

By Crystal Lindell

An FDA-approved test that claims it can identify genetic risk for opioid use disorder (OUD) is so flawed as to basically be useless – at least according to a new study published in JAMA.

The genetic test, which is sold under the brand name “AvertD” by AutoGenomics, was given approval by the Food and Drug Administration in 2023. The test claims it can use 15 genetic variants to identify people at risk for misusing opioids. 

According to AutoGenomics, the variants “may be associated with an elevated genetic risk for developing OUD.” However, the company provides no citations to support the associations between the brain reward pathways and OUD — meaning the test’s foundation itself seems to be flawed.

However, the authors took the premise of the AvertD test seriously, and set out to find if it could actually predict OUD. They looked at a diverse sample of more than 450,000 “opioid-exposed individuals” (including 33,669 individuals with OUD), and found no evidence to support the use of the AvertD test. 

Specifically, they found both high rates of false positives and false negatives, with 47 out of 100 predicated cases or controls being incorrect. 

“Notably, clinicians could better predict OUD risk using an individual’s age and sex than the 15 genetic variants,” researchers said.

The fact that the test doesn’t seem to work could have dangerous consequences for pain patients. The fear is that they will be used to deny patients opioid medications simply because their “genetic markers” show them to be in a high-risk patient group. 

The study authors directly point this out, writing: “False-positive findings can contribute to stigma, cause patients undue concern, and bias health care decisions.”

They also point out the potential harms of a false-negative finding, which "could give patients and prescribers a false sense of security regarding opioid use and lead to inadequate treatment plans."

The fact that this genetic test has gotten as far as it has raises questions about the FDA approval process. 

The problems don’t stop there though. Another major flaw in both the study and the genetic testing is that “Opioid Use Disorder” has such murky diagnostic criteria, that it’s difficult to take it seriously. It’s basically a set of vague symptoms, as opposed to a clear-cut diagnosis, despite what some have been led to believe. 

A CDC fact sheet for OUD Diagnostic Criteria is a mishmash of vague symptoms, such as tolerance and withdrawal, that could just be the result of untreated or poorly treated physical pain. 

Things like “taking opioids in larger amounts or over a longer period of time than intended” and “having a persistent desire or unsuccessful attempts to reduce or control opioid use.”

The CDC also lists "withdrawal symptoms" as one of the diagnostic criteria for OUD, which is something that people can experience from rapid tapering without having OUD.

The CDC then includes the odd disclaimer that “tolerance and withdrawal are not considered” when opioids are taken under appropriate medical supervision.

So in a country that does not guarantee healthcare, you can avoid an OUD diagnosis if you can afford to find a doctor willing to prescribe opioids to you. But if you can’t find a doctor or abandoned by one — and then have withdrawal symptoms — you must have a disorder.

That doesn’t sound like a medical diagnosis to me. That sounds like classism.

A patient needs just to have just two of the OUD criteria to have “mild OUD” – a benchmark that has the sweeping effect of including a large number of patients taking opioids for chronic pain. 

It’s no wonder that a genetic test claiming to be able to predict OUD would be so flawed, given how flawed the diagnosis of OUD is to begin with. 

Perhaps instead of trying to guess potential risks for a vague disorder, the FDA should be focused on treatments already proven effective for people who want to stop their opioid use, like expanding methadone access. 

The whole situation reminds me of the Tom Cruise-movie Minority Report, a futuristic thriller in which a specialized police department called Precrime “apprehends criminals by use of foreknowledge provided by three psychics.”

Denying people pain medication based on a flawed genetic test that falsely claims it can predict the future is basically the same thing. And it’s just as evil in real life as it is in the movie.  

More Lackluster Results for Non-Opioid Pain Reliever

By Pat Anson

New questions are being raised about the effectiveness of an experimental non-opioid analgesic and whether it can be a viable alternative to opioid pain medication.

Results from Vertex Pharmaceuticals’ Phase 2 clinical trial show that suzetrigine is essentially no more effective than a placebo in relieving back and hip pain caused by lumbosacral radiculopathy (LSR).

After 12 weeks of treatment with the drug suzetrigine, patients with LSR had a 2.02 average reduction in their pain scores on a rating scale of zero to 10. That compares to an average reduction of 1.98 for patients who received a placebo or sham treatment.

Although the difference between 2.02 and 1.98 is minuscule, Vertex claimed the overall findings were “statistically significant and clinically meaningful” in a press release. The company blamed the lackluster results on the placebo effect and the difficulty of treating lumbosacral radiculopathy.

“Suzetrigine has again demonstrated its potential to fill an important unmet need in the treatment of pain,” said Carmen Bozic, MD, Executive Vice President and Chief Medical Officer at Vertex. “We did not see separation between the suzetrigine and the placebo arms. Yet our post-hoc analyses suggest that this could be due to the high placebo response in this study.”

Despite the disappointing results, Vertex still plans to go ahead with a Phase 3 study of suzetrigine for LSR, while changing the study design to minimize the impact of the placebo.

“Managing the placebo response in pain trials is a complex challenge. We look forward to innovating in clinical trial design, including for the pivotal study, with the aim of bringing a potentially safe and effective treatment to patients suffering from LSR," said Christine Sang, MD, co-chair of Vertex’s Peripheral Neuropathic Pain steering committee and principal investigator of the study.

Suzetrigine is already under consideration by the FDA as a treatment for acute pain, with a decision expected in late January. If approved, suzetrigine would be the first new medication for acute pain in over two decades.

Unlike opioids, suzetrigine blocks pain signals in the peripheral nervous system before they reach the brain. That means it won’t have the “liking” effect that opioids can have in some patients or be as addictive.

Although suzetrigine has been touted as a novel painkiller that "could bring relief to millions” without the risk of addiction, findings from earlier studies have also been mixed. In a Phase 3 trial of patients recovering from minimally invasive surgery, suzetrigine was no more effective than a low dose combination of hydrocodone and acetaminophen, more commonly known as Vicodin.

Although Vertex downplayed the results from the Phase 2 study, shares of the company lost about 15% of their value after last week’s announcement. Wall Street analysts said the Phase 2 findings were “very messy” and "raise considerable risk around suzetrigine's potential.”

Ultimately, it will be up to the FDA to decide whether suzetrigine should be allowed on the market. The agency is under pressure to approve new non-opioid analgesics, so it may look past the disappointing clinical trial findings. If approval is granted in January, it will coincide with implementation of the NOPAIN Act, which will make non-opioid analgesics in outpatient surgical settings eligible for higher Medicare reimbursement rates.  

In addition to acute pain and lumbosacral radiculopathy, Vertex is also studying suzetrigine as a treatment for diabetic peripheral neuropathy.

Kratom Still Widely Available Despite Safety Concerns

By Pat Anson

Kratom may be banned in six U.S. states and dozens of cities and counties, but the herbal supplement is still widely available in tobacco and vape stores despite concerns about its safety, according to a new study.

Kratom has been used in southeast Asia for centuries as a natural stimulant and pain reliever. In recent years, millions of Americans have discovered that kratom can be used to treat pain, anxiety, depression and addiction. The FDA, however, has not approved kratom for any medical condition and warns that it may cause addiction and overdoses.

“The FDA has serious safety concerns with the use of kratom in dietary supplements and conventional foods. Based on the available scientific data and information, the FDA has concluded that kratom is not lawfully marketed as a dietary supplement,” the agency warned.

To see whether those warnings are taken seriously, a team of academic researchers contacted 520 tobacco and vape shops across the United States to see if they were selling kratom.

"I spent my nights and weekends for about three, four weeks making these calls and just asking," Matthew Rossheim, PhD, Associate Professor at the University of North Texas Health Science Center, said in a press release. "What we found is that these products are widely available."

In states where kratom is legal, Rossheim and his colleagues found that over 80% of tobacco and vape stores were selling it. But even in the states where kratom and its alkaloids (mitragynine and 7-hydroxymitragynine) are banned – Rhode Island, Alabama, Arkansas, Indiana, Vermont and Wisconsin – some merchants freely admit selling kratom products. In Rhode Island, 40% of the surveyed establishments reported selling the illegal supplement.

UNIVERSITY OF MISSISSIPPI GRAPHIC

"This product, it's being marketed as being a mood stabilizer and painkiller, but then we also have several warnings from federal agencies and people who have died from overdoses," said Andrew Yockey, PhD, Assistant Professor of Public Health at the University of Mississippi. "That is the disconnect, right? There are people who think this is a fantastic product, but it's also linked to these poisonings and hospitalizations.”

About 100 deaths have been linked to kratom use, but in the vast majority of cases other drugs and illicit substances were involved.  

The family of a 23-year-old Georgia man, who died in 2021 after ingesting a potent kratom extract, filed a wrongful death lawsuit against the extract’s manufacturer. Despite the lawsuit, Black Liquid Kratom can still be purchased online, even though one kratom vendor warns the extract is “too strong for use on a daily basis.”

"One of the biggest health things that we're seeing is that these products are hitting the market without supervision," said Yockey. "And if there's no supervision, do you really know what you're putting in your system?"

Dietary supplements are loosely regulated in the United States and kratom is no exception. The American Kratom Association (AKA) is trying to improve the safety and quality of kratom through its GMP standards program, which requires participating vendors to complete an annual independent audit of their manufacturing, processing, and labeling of kratom products.

The AKA is also encouraging individual states to adopt the Kratom Consumer Protection Act, which requires vendors not to adulterate kratom products or to sell kratom in any form to consumers under the age of 18. Nevada, Utah, Arizona and Georgia have adopted similar measures of the bill.

Thailand recently adopted new regulations on the use of kratom in food and herbal products. The guidelines require kratom vendors to register with the Thai Food and Drug Administration and to meet safety and labeling standards. Kratom was listed as an illegal narcotic in Thailand until 2021, but is now regulated under the Kratom Plant Act, which allows for the use, selling, import and export of kratom. No such laws exist at the federal level in the United States.

FDA’s New Rules Aim to Make Pharma Ads Easier to Understand

By Crystal Lindell

The Food and Drug Administration is hoping that its new rules will make pharmaceutical ads on TV and radio easier to understand. 

Commercials for pharmaceutical drugs must now include a “major statement” about side effects and contraindications in “a clear, conspicuous, and neutral manner.” The rule applies to direct-to-consumer (DTC) ads for prescription drugs and what conditions they are used to treat. 

The new regulations are a response to something many drug makers figured out long ago: people tend to tune out when they start to hear a long list of potential side effects and interactions, which are usually rushed through at the end of drug commercials. By then, consumers may have tuned out the downsides of the medication. 

“If you’re a company and you’re worried about possible FDA enforcement or product liability and other litigation, all your incentives are to say more, not less,” Torrey Cope, a food and drug lawyer, told the AP.

The law firm Lerman Senter broke down the five new standards the FDA requires companies to meet in drug ads. All commercials must now include:

1. Consumer Friendly Language: Ads must clearly state the name of the drug, and a major statement of side effects must be presented in language that is readily understandable. It should not include technical or medical jargon.
   

2. Understandable Audio: Audio information must be understandable in terms of volume, articulation and pacing, and should be as understandable as the rest of the commercial. “Rapid fire” disclosures will no longer be permitted.
   

3. Major Statement Must Be Presented Concurrently in Text and Audio: Television ads must present the major statement simultaneously in the audio and visual sections.
   

4. Text Must Be Easily Readable: The on-screen text must be presented against a contrasting background for sufficient duration, and in a font size and style that is easily readable.
   

5. No Distractions. Advertisements cannot have statements, text, images or sounds that detract from comprehension of the major statement. No other sounds, including music or catchy jingles, should be heard during the side effects disclosure.

While the rule went into effect a few months ago, companies have until November 20 to be in full compliance. So while you may have already noticed pharma ads changing, all of them should be in compliance starting this week. 

In its report about the changes, the FDA said that while drug ads often have a caveat urging people to “ask your doctor” about a medication, pharmaceutical companies are incentivized to make the ads deceptive in various ways. 

“Like all advertisers, prescription drug firms have ample business incentives to present their products in a positive light to potential consumers,” the FDA said. “But those business incentives do not assure clear communication of the advertised drug’s negative attributes to consumers.”

While no federal law has ever banned pharmaceutical companies from directly advertising to consumers, the practice didn't really take off until about 40 years ago. Currently, the United States and New Zealand are the only two countries that allow DTC drug advertising. 

In its report, “Background on Drug Advertising,” the FDA explains: 

"Until the mid-1980s, drug companies gave information about prescription drugs only to doctors and pharmacists. When these professionals thought it appropriate, they gave that information to their patients. However, during the 1980s, some drug companies started to give the general public more direct access to this information through DTC ads."

As someone who was born in the mid 1980s, I remember being surprised as an adult when I learned that most other countries ban pharma companies from advertising directly to consumers. 

While it’s difficult to imagine that the U.S. would ever ban the ads completely, there’s definitely a good case for heavily regulating them. A 2005 study found pharmaceutical ads that encouraged consumers to talk with their doctors “have a profound effect on physician prescribing” and could promote overuse or inappropriate prescribing.

In other words, drug companies are very good at creating ads that make people want to buy their products, whether they need them or not. Let’s be real: if drug advertising didn’t work, companies would not be spending over $15 billion a year promoting their medications. 

I’m glad to see the FDA amping up these regulations, so people have a better understanding of drug ads. But it remains to be seen how these agency regulations will hold up under the incoming Trump administration.   

Return to Sender: WIll Anyone Use FDA’s New Opioid Mail-Back Program?

By Crystal Lindell

The DEA has been hosting drug “Take Back Days” for over a decade, collecting over 9,200 tons of unwanted or expired prescriptions and over-the-counter medicines. The take-back program is seen as a key effort to prevent drug diversion and opioid addiction.

Now the Food and Drug Administration is expanding its own drug collection program – essentially making every day an opioid take-back day.  

Starting on March 31, 2025, drug makers participating in the FDA’s Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)  – which means every company that makes and sells opioids – will be required to provide pre-paid, drug mail-back envelopes “upon request” to pharmacies that dispense opioids. The pharmacies then have to give the envelopes to patients and caregivers who ask for them, so they can mail back any unwanted opioids. 

The fact that both pharmacies and patients have to request these envelopes makes me skeptical about how much this program will actually be used.

The press release from the FDA includes a quote that sounds surprisingly pro-patient though. So even if the program doesn’t have a high use-rate, perhaps an extra measure of safety will make it easier for patients to get opioid prescriptions. 

“We want to ensure patients have access to opioid analgesics in their pain management regimens and that they are educated about methods available to safely dispose of any leftover medicines, which could pose a real danger to their loved ones and pets,” said Marta Sokolowska, PhD, deputy center director for Substance Use and Behavioral Health at the FDA Center for Drug Evaluation and Research.  

It’s the part about ensuring that “patients have access to opioid analgesics” that stands out to me. Patients certainly need access to opioid pain meds. And if programs like this help doctors and medical professionals feel more comfortable prescribing opioids, then I fully support them. 

But I’m skeptical about whether that will be the actual outcome. The real question is whether anyone will use the mail-back program. 

The DEA has never released a full breakdown of the medications returned during its drug take-back days. But an analysis of the drugs returned at a take-back day in Lansing, Michigan in 2013 provides some insight. 

Of the nearly 2,500 medication containers that were returned, only 304 were for a controlled substance like opioids – about 12% overall. The most common types of medication returned were for pain/spasm, cardiovascular, and mental health conditions.

While hydrocodone/acetaminophen combinations (Norco) were the most returned medication at that 2013 event, it represented just 4.4% of all returned containers. 

The second most-common drug returned was ibuprofen (Advil) in 2.2% of the containers. Acetaminophen (1.7%) and aspirin (1.3%) also made the top ten list of most-returned medications. 

Something tells me that Advil isn’t what organizers had in mind when they asked people to bring in their unused drugs. 

In the end, the FDA’s new mail-back program will likely have a greater impact as a public relations initiative to make the agency look good, rather than keeping unwanted opioids off the street. 

In a world where doctors are so reluctant to prescribe opioids, I don’t blame people for wanting to hold on to the opioids they’re able to get. In a PNN survey of thousands of pain patients, nearly a third (32%) admitted hoarding their unused opioids because they’re unsure if they’ll be able to get them in the future 

If we’re lucky, the program will accomplish at least one of the goals that the FDA’s Sokolowska laid out: “We want to ensure patients have access to opioid analgesics.”

Given the federal government's abysmal track record with opioids and pain care in general, I’ll believe that when I see it.

Cancer Patients Abandoned When Fentanyl Painkillers Discontinued

By Pat Anson

Patients suffering from severe cancer pain are scrambling to find alternatives after a drug maker discontinued production of potent fentanyl analgesics.

Cephalon, which is owned by Teva Pharmaceuticals, notified the FDA in August that it was stopping production of Transmucosal Immediate-Release Fentanyl Medicines, known as TIRF medications. The FDA then told patients and prescribers that all TIRF meds would be discontinued on September 30.  

“The moment I heard TIRF medicine was being discontinued, I was nearly brought to tears because I fear going back to the way things were before.  I have until the supply runs out and that's it,” said Anthony, a 46-year-old Georgia man who has severe headaches from an inoperable brain tumor. He asked that we not use his last name. 

Anthony has been taking TIRF meds since 2016. He also had a pain pump surgically implanted to deliver opioids around-the-clock, but still needed TIRF for occasional breakthrough pain.

“To transition back to traditional opiates will be a major step back treating my breakthrough pain,” Anthony explained. “Before TIRF medications, I struggled, and my quality of life followed suit.  I spent more time laying horizontal in my bed. It's been a long battle. I'm lucky to still be here.”

TIRF meds are effective because they are absorbed quickly through the mouth and provide pain relief within minutes. The two meds discontinued by Teva are Actiq, a fentanyl lozenge, and Fentora, a fentanyl buccal tablet that dissolves in the mouth.

“Because both of these meds and possibly other forms of TIRF medications bypass the gastrointestinal tract, they are overwhelmingly beneficial in my breakthrough pain,” says Anthony, who is regularly drug tested to make sure he isn’t abusing TIRF.

“I do not get high or feel euphoria.  If I abused these meds that might be an issue, but I take as prescribed.  Plus, if I took more than intended, I would run out of meds before my next refill leaving me without.  Not to mention, I don't want to stop breathing.”   

‘I Think They’re Good Drugs’

Because TIRF medication is made with fentanyl, a synthetic opioid 100 times more potent than morphine, it is poorly understood by the public and often demonized by anti-opioid activists.

Illicit fentanyl is involved in about 70% of fatal overdoses, but prescription fentanyl is rarely diverted and has long played an essential role in treating severe pain. Less than one-tenth of one percent of prescription fentanyl – 0.088% -- is diverted, according to DEA estimates.

“I think breakthrough pain is a horrible thing, and I think these patients really benefit from these breakthrough pain medications,” said Tom Jenkins, PhD, Chief Scientific Officer and Co-Founder of Elysium Therapeutics, which is developing a new class of opioids with less risk of abuse.

“These transmucosal fentanyl drugs are really complementary to the profile of the breakthrough pain and really help patients manage it quite effectively. I think they're good drugs. I don't think they're widely prescribed, so I think the diversion of them is not as significant of a problem.”

Despite that, an op/ed being published in U.S. newspapers refers to TIRF meds as “candy” and “lollipops” – implying they are widely abused and marketed to children, not cancer patients.

“The withdrawal of these potent, short-acting fentanyl products is good news, but they never should have been approved in the first place,” wrote Dr. Adriane Fugh-Berman and Judy Butler, who are affiliated with PharmedOut and Physicians for Responsible Opioid Prescribing (PROP).

“Classified as transmucosal immediate-release fentanyl or TIRF products, these delivery methods are highly potent and highly addictive. The faster an addictive substance enters the bloodstream, the more abuse potential it has. TIRFs acted almost as fast as opioids used intravenously, and addicted many people.”

Fugh-Berman and several other PROP members have collectively been paid several million dollars by plaintiff law firms to be consultants or expert witnesses in opioid litigation, a detail not mentioned in the op/ed or by the news organizations that published it.

Adverse Events

It’s true that TIRF medications have been abused, but many of those cases involved Subsys, an oral fentanyl spray that was illegally marketed by Insys Therapeutics. Insys filed for bankruptcy in 2019, and the company’s founder and several top executives were later convicted of racketeering and bribing doctors.

According to the FDA, adverse events involving TIRF peaked in 2018, with nearly 22,000 reported cases. Since then, they’ve fallen by about 80%.

The decline in adverse events coincided with a steep drop in the number of cancer patients enrolled in the FDA’s Risk Evaluation and Mitigation Strategy (REMS) Program, which facilitated the safer prescribing of TIRF. Over 4,700 patients were enrolled in the TIRF program in 2017. Today there are fewer than 150.

Anthony is one of them.

“The small number of people on the meds are a result of the FDA strengthening the REMS requirements, making it a huge headache for doctors to not only prescribe TIRF meds, but also to keep patients on them, making so much extra work for the doctors,” Anthony told PNN. “Too much red tape involved, so doctors avoid like the plague.”

Another factor is cost. A supply of Actiq or Fentora that might last a few days or weeks for a cancer patient in severe pain will cost thousands of dollars. The drugs are often not covered by insurance.

‘It’s Opioid Phobia’

Why did Teva stop making TIRF medication? The company has not made any public statements about the discontinuation of Actiq and Fentora, and did not reply to PNN requests for comment.

The most likely explanation is that Teva’s bottom line was suffering, due in part to the costs of opioid litigation. In 2008, its Cephalon subsidiary paid a $425 million fine for the off-label marketing of Actiq and two other drugs. Then in 2022, Teva agreed to pay $4.25 billion to settle thousands of opioid liability lawsuits.

Last year, as part of a strategic restructuring, Teva discontinued production of generic oxycodone to focus on more profitable branded drugs.

“It's opioid phobia. I think these companies were spooked by the lawsuits. Maybe some of them did misbehave a little bit and deserved it,” said Elysium’s Jenkins. “I feel for the patients that were using these things appropriately, were getting relief, that are no longer able to access the drug.

“I can only imagine corporate lawyers were just saying, ‘Hey, this isn't worth it. Let's get out of this.’ And also the REMS program. I mean, the FDA is deliberately making it difficult for physicians to prescribe this drug, right?”

Caught in the middle of opioid litigation and a profit-driven healthcare system are cancer patients like Anthony.

“I do not feel the few remaining patients should be made to suffer by discontinuing TIRF medications.  I'm guessing they are doing this because it's no longer as profitable as it once was,” he said. “Why can't small batches be done to maintain the quality of life of the remaining TIRF patients?”

The FDA has shown no interest in keeping the REMS program alive by finding a new TIRF manufacturer. New applications from patients and prescribers are no longer being accepted. And calls to the program’s hotline go unanswered.

“FDA did not request this discontinuation. It is important to note that FDA does not manufacture medicine and cannot require a pharmaceutical company to make a medicine, make more of a medicine, or change the distribution of a medicine,” the agency said in a brief online statement.

FDA Shutting Down Fentanyl Access Program for Cancer Patients

By Pat Anson

The U.S. Food and Drug Administration is shutting down a pain management program that helped supply fentanyl medication to patients suffering from severe cancer pain.

In a notice published on the FDA’s website for its Transmucosal Immediate-Release Fentanyl Medicines (TIRF) program, the agency said that all TIRF medications “will be discontinued” on September 30.

The program was created due to the risks associated with fentanyl, a synthetic opioid 100 times more potent than morphine. The FDA has required a Risk Evaluation and Mitigation Strategy (REMS) for TIRF medications since 2011.

“Patients currently enrolled in the TIRF REMS may continue their TIRF therapy while supplies remain,” the FDA notice states. “Prescribers currently certified in the TIRF REMS may continue to prescribe TIRF therapy for their currently enrolled patients while supplies remain but must begin working with their patients to transition to other non-TIRF treatments.”

TIRF-REMS has also stopped accepting new applications from patients, prescribers, pharmacies and wholesale drug distributors. According to the FDA, 4,722 patients received a TIRF medication in 2017, but there are currently fewer than 150 patients getting them.

Illicit fentanyl is a notorious street drug that is involved in about 70% of fatal U.S. overdoses. But prescribed fentanyl has long been an essential medicine for patients suffering from surgical pain, breakthrough pain and cancer-related pain. It is also prescribed “off-label” for other types of severe pain.

FDA TIRF-REMS UPDATE

The FDA’s decision to end TIRF-REMS came after Cephalon, which is owned by Teva Pharmaceuticals, notified the agency in August that it was discontinuing production of Actiq, a fentanyl lozenge, and Fentora, a fentanyl buccal tablet. Both medications are absorbed into the bloodstream quickly through the mouth to provide immediate pain relief.  

(Update: On September 16, FDA published a brief statement confirming that TIRF medications are being discontinued, but said the TIRF-REMS program would continue operating while supplies last.

“The TIRF REMS will remain in place as long as the manufacturers’ new drug applications or abbreviated new drug applications are approved, regardless of the marketing status of the products,” the agency said. “FDA did not request this discontinuation. It is important to note that FDA does not manufacture medicine and cannot require a pharmaceutical company to make a medicine, make more of a medicine, or change the distribution of a medicine.”

Teva did not respond to requests for comment about the discontinuations. Actiq and Fentora are expensive medications. A supply of 30 Actiq 400 mcg lozenges costs about $3,500, while 28 tablets of Fentora 100 mcg will cost about $2,300.

“I had very few patients on these medications in the past, since no health insurers would actually pay for them,” said Chad Kollas, MD, a palliative care physician and pain policy expert. “I think it’s problematic that the TIRF-REMS website isn’t offering recommendations for an effective alternative approach for the patients currently using TIRF products.”

Opioid litigation and the risk of further liability may have influenced Teva’s decision to discontinue TIRF medication. The company agreed to pay $4.24 billion to settle allegations that it illegally marketed opioids and failed to prevent their diversion.

Last year, Teva discontinued production of immediate release oxycodone as part of a strategic shift away from less profitable generic drugs.

FDA Clears New Prescription-Only TENS Device

By Pat Anson

Transcutaneous electrical nerve stimulation – more commonly known as TENS – uses mild electric currents to temporarily relieve pain in sore muscles and tissues. Some TENS units are elaborate wearable devices that cost hundreds of dollars, while others are simple gadgets that can be purchased online or over-the-counter for about $30.

Due to lingering questions about their effectiveness, many health insurers don’t cover TENS devices, while others make patients jump through hoops to get reimbursed for them.

Medical device maker Zynex Medical is hoping to bridge the gap in insurance coverage with a new TENS device called TensWave, which is only available by prescription. The company says the FDA has “cleared” TensWave for marketing, allowing sales to begin immediately.

"The introduction of TensWave aligns perfectly with our commitment to providing comprehensive pain management solutions," Thomas Sandgaard, CEO of Zynex, said in a press release.

"We recognized a gap in the market for a high-quality TENS device that meets the specific criteria for insurance reimbursement, and TensWave is our answer to that demand. It complements our flagship multi-modality device, the NexWave, where Interferential current is the main modality and driver of obtaining prescriptions. This device broadens our product portfolio and enhances our support to patients."

ZYNEX IMAGE

Unlike NexWave, which has three different electrical stimulation modalities, TensWave only uses TENS technology, which Zynex believes will make it easier to get insurance coverage. The company currently has no estimate of TensWave’s cost if a patient has to buy it out-of-pocket.   

In its press release, Zynex said TensWave “has been clinically proven to reduce chronic and acute pain,” which is a bit of an exaggeration, because the device did not go through the FDA’s lengthy review and approval process. However, because TensWave has “substantial equivalence” to other TENS units already on the market, it was cleared for sale without ever undergoing a clinical trial to prove its safety and efficacy. This is a common practice allowed by the FDA when new medical devices are introduced.

The World Health Organization takes a dim view of TENS, saying the evidence of its effectiveness in relieving chronic lower back pain is “very low” due to a limited number of clinical trials. In some trials, TENS worked no better than a placebo.

The UK’s National Health Service (NHS) has a similar view of TENS, saying there is not enough good-quality evidence to recommend its use as a reliable method of pain relief.

“Healthcare professionals have reported that it seems to help some people, although how well it works depends on the individual and the condition being treated,” the NHS states. “TENS is not a cure for pain and often only provides short-term relief while the TENS machine is being used.”