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.

Liability Trial of Opioid Drug Maker Could Set Precedents

By Jackie Fortier, Kaiser Health News

All eyes will be on Oklahoma this week when the first case in a flood of litigation against opioid drug manufacturers begins. Oklahoma Attorney General Mike Hunter’s suit alleges Johnson & Johnson, the nation’s largest drugmaker, helped ignite a public health crisis that has killed thousands of state residents.

With just two days to go before the trial, one of the remaining defendants, Teva Pharmaceutical, announced an $85 million settlement with the state on Sunday. The money will be used for litigation costs and an undisclosed amount will be allocated “to abate the opioid crisis in Oklahoma,” according to a press release from Hunter’s office.

In its own statement, Teva said the settlement does not establish any wrongdoing on the part of the company, adding Teva “has not contributed to the abuse of opioids in Oklahoma in any way.”

That leaves Johnson & Johnson as the sole defendant.

Court filings accuse the company of overstating the benefits of opioids and understating their risks in marketing campaigns that duped doctors into prescribing the drugs for ailments not approved by regulators.

The bench trial — with a judge and no jury — is poised to be the first of its kind to play out in court.

Nora Freeman Engstrom, a professor at Stanford Law school, said lawyers in the other cases and the general public are eager to see what proof Hunter’s office offers the court.

“We’ll all be seeing what evidence is available, what evidence isn’t available and just how convincing that evidence is,” she said.

Most states and more than 1,600 local and tribal governments are suing drugmakers and distributors. They are trying to recoup billions of dollars spent on addressing the fallout tied to opioid addiction.

Initially, Hunter’s lawsuit included Purdue Pharma, the maker of OxyContin. In March, Purdue Pharma settled with the state for $270 million. Soon after, Hunter dropped all but one of the civil claims, including fraud, against the remaining defendants. Teva settled for $85 million in May, leaving Johnson & Johnson as the only opioid manufacturer willing to go to trial with the state.

But he still thinks the case is strong.

“We have looked at literally millions of documents, taken hundreds of depositions, and we are even more convinced that these companies are the proximate cause for the epidemic in our state and in our country,” Hunter said.

The companies involved have a broad concern about what their liability might be, said University of Kentucky law professor Richard Ausness.

“This case will set a precedent,” he said. “If Oklahoma loses, of course they’ll appeal if they lose, but the defendants may have to reconsider their strategy.”

With hundreds of similar cases pending — especially a mammoth case pending in Ohio — Oklahoma’s strategy will be closely watched.

“And of course lurking in the background is the multi-state litigation in Cleveland, where there will ultimately be a settlement in all likelihood, but the size of the settlement and the terms of the settlement may be influenced by Oklahoma,” Ausness said.

Rx Opioids ‘Useful Products’

The legal case is complicated. Unlike tobacco, where states won a landmark settlement, Ausness pointed out that opioids serve a medical purpose.

“There’s nothing wrong with producing opioids. It’s regulated and approved by the Food and Drug Administration, the sale is overseen by the Drug Enforcement Administration, so there’s a great deal of regulation in the production and distribution and sale of opioid products,” Ausness said. “They are useful products, so this is not a situation where the product is defective in some way.”

It’s an argument that has found some traction in court. Recently, a North Dakota judge dismissed all of that state’s claims against Purdue, a big court win for the company. In a written ruling that the state says it will appeal, Judge James Hill questioned the idea of blaming a company that makes a legal product for opioid-related deaths.

“Purdue cannot control how doctors prescribe its products and it certainly cannot control how individual patients use and respond to its products,” the judge wrote, “regardless of any warning or instruction Purdue may give.”

Now the Oklahoma case rests entirely on a claim of public nuisance, which refers to actions that harm members of the public, including injury to public health.

“It’s sexy you know, ‘public nuisance’ makes it sound like the defendants are really bad,” Ausness said.

If the state’s claim prevails, Big Pharma could be forced to spend billions of dollars in Oklahoma helping ease the epidemic. “It doesn’t diminish the amount of damages we believe we’ll be able to justify to the judge,” Hunter said, estimating a final payout could run into the “billions of dollars.”

Hunter’s decision to go it alone and not join with a larger consolidated case could mean a quicker resolution for the state, Ausness said.

“Particularly when we’re talking about [attorneys general], who are politicians, who want to be able to tell the people, ‘Gee this is what I’ve done for you.’ They are not interested in waiting two or three years [for a settlement], they want it now,” he said. “Of course, the risk of that is you may lose.”

Oklahoma has the second-highest uninsured rate in the nation and little money for public health. Of the $270 million Purdue settlement, $200 million is earmarked for an addiction research and treatment center in Tulsa, though no details have been released. An undisclosed amount of the $85 million Teva settlement will also go to abating the crisis.

This story is part of a partnership that includes StateImpact Oklahoma, NPR and Kaiser Health News. KHN is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Soaring Cost of Multiple Sclerosis Drugs 'Alarming'

By Pat Anson, Editor

The cost of drugs used to treat multiple sclerosis (MS) in the United States has soared as much as 700 percent in the past two decades, according to researchers who call the price escalation “alarming” and possibly coordinated by drug companies.

There are no multiple sclerosis drugs now available in the U.S. with a list price below $50,000 a year, which is two to three times more than the price of the same drugs in Canada, Australia or the United Kingdom. Prices of MS drugs rose at five to seven times the rate of drug inflation in the U.S.

“The coordinated price escalations for these therapies has lead to increasing access and affordability problems for patients with MS. Pricing decisions by pharmaceutical companies need to better reflect the financial realities and constraints of our healthcare system as opposed to a strategy of whatever our dysfunctional market will bear,” said Daniel Hartung, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, in an email to Pain News Network.

Hartung is the lead author of a scathing new study appearing in the journal Neurology, which blames the soaring cost of MS drugs on the greed of drug companies and the inability of a national healthcare system to negotiate drug prices.

"The simplest explanation is that pharmaceutical companies raise prices of new and old MS disease modifying therapies in the United States to increase profits, and our healthcare system puts no limits on these increases," the researchers wrote in their report. "The U.S. Medicare program, the largest single-payer healthcare system in the U.S., is legally prohibited from negotiating drug prices directly with the pharmaceutical industry.

“Government-issued patent monopolies, third-party payers, lack of reimbursement transparency, and imperfect clinical information all contribute to a seemingly dysfunctional marketplace where expanded choice has led to higher, rather than lower, prices. Some argue that recent trends in industry pricing suggest collusive behavior between manufacturers, although this is challenging to prove with price data alone.”

Pricing Defies "Common Sense"

The researchers cite several examples of older MS drugs rising in price decades after they were approved by the Food and Drug Administration – and long after pharmaceutical companies recovered the cost of developing the medications.

The annual cost of Copaxone, for example, was $8,292 when it was introduced in 1996 by Teva Pharmaceuticals. Today it is $59,158 – over seven times higher.

Avonex, another early MS treatment, had an annual cost of $8,723 when it was introduced by Biogen in 1996. Today it is $62,394 – also seven times higher.

"Economics 101 would suggest that competition should lower prices. In the pharmaceutical industry we often don't see that. Many professionals now believe that it's time to push back, to say enough is enough," said Hartung.

“What has happened defies common sense, logic, and the expected rules of the marketplace,” wrote T. Jock Murray, MD, in an editorial about Hartung’s study also published in Neurology. “These counter-intuitive increases suggest the possibility of collusion among the manufacturers, but the authors say they do not have evidence.

“What justification does the pharmaceutical industry in the United States offer for the remarkable increase in the costs of these drugs? Well, they do not have to explain, as they are allowed to set prices in a black box, based on the business ethic of maximizing profit, supported by a bizarre law that prevents Medicare from negotiating prices directly with the pharmaceutical industry.”

“We cannot comment on the practices or products of other companies,” said Kate Niazi-Sai, a spokesperson for Biogen in an email to Pain News Network.

“What we can say is that since its introduction as one of the first MS therapies two decades ago, Avonex has helped many thousands of people with MS, who before then had no treatment options.  Since then revenue from Avonex has enabled the development of improved treatments so that today, patients have a breadth of options they need to deal with MS.”

Niazi-Sai said Biogen offers discount programs and free medicines to needy patients worth hundreds of millions of dollars each year. But that’s a fraction of what the company makes from MS drugs.

According to first quarter financial results released by Biogen, sales of Avonex and other MS therapies were $2.1 billion, compared to $1.7 billion in the same quarter last year.

Niazi-Sai said the money is put to good use.

“Revenue from our therapies for MS and hemophilia are now fueling the search for a way to reverse or possibly cure MS, as well as new treatments for Alzheimer’s disease, Lou Gehrig’s disease and other devastating medical conditions.  We are eager to be part of any thoughtful discussion about funding medical advances. Anyone who believes there is a better way should propose it," she wrote.

Teva Pharmaceuticals declined to comment on its pricing policies, but said in a statement to Pain News Network that “the wholesale acquisition cost for Copaxone is competitive to other branded molecules in this category. It is reflective of investments made to research, develop and commercialize a safe and effective relapsing MS product.”

MS is a chronic and incurable disease which attacks the body’s central nervous system, causing numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain.

Escalating costs for MS therapies and other specialty drugs are a growing concern in the healthcare industry. A recent study said the cost of treating rheumatoid arthritis with new biologic drugs has become a “significant financial burden” for many patients. Patients enrolled in Medicare Part D plans paid an average out-of-pocket cost of $835 a month for a biologic drug in 2013. Costs varied widely depending on the drug – from $269 to $2,993 a month.

"Pricing in the pharmaceutical industry increasingly is a case of whatever the market will bear," Hartung said. "We used to think that any drug with $1 billion in sales was a blockbuster, but last year a drug for hepatitis C had 10 times that, or $10 billion in sales. This does not necessarily mean that drug research and innovation will be 10 times better.”