By DAMIAN GARDE @damiangarde OCTOBER 9, 2019

Since its recall in 2004, the pain drug Vioxx has been a symbol of pharmaceutical danger, starring in countless daytime legal advertisements explaining how you, or perhaps a loved one, might be entitled to millions in settlement dollars. But one company believes the infamous drug deserves a second chance, and is plotting to resurrect the former blockbuster as a treatment for a rare, incurable condition.

Vioxx’s days as a widely used treatment for arthritis and chronic pain came to an end when studies revealed that it roughly doubled patients’ risk of heart attack and stroke, leading to an estimated 60,000 deaths. It was a public health disaster, and it led to a congressional investigation, allegations of lapses at the Food and Drug Administration, and agreement by the manufacturer, Merck, to pay a nearly $5 billion settlement.

Now, Tremeau Pharmaceuticals, a private Massachusetts company, is developing a generic version of Vioxx as a treatment for severe joint pain in people with hemophilia, a side effect called hemophilic arthropathy. The company plans to begin a pivotal trial next year and, if the resulting data are positive, Tremeau will apply for FDA approval in hopes of bringing Vioxx back to market more than 15 years after Merck pulled it from shelves.

Experts say the drug’s cardiovascular issues are nothing to discount, but Vioxx’s deadly history isn’t doomed to repeat itself. The alarming number of heart attacks associated with the drug represent a small percentage of the millions of people who took it, driven in part by the fact that doctors prescribed liberally. Now that Vioxx’s relationship with cardiovascular danger is well-understood, they say, doctors could mitigate future problems by ensuring that patients at high risk don’t get it, and by consistently monitoring those who do.

While the Vioxx brand might be tarnished in the popular consciousness, the drug has a much different reputation in the hemophilia community. Before its recall, the drug was the off-label drug of choice to treat hemophilic arthropathy, which results from a buildup of blood in patients’ joints and leads to pain, inflammation, and tissue damage. Over-the-counter pain treatments like ibuprofen can lead to internal bleeding, making them inadvisable for patients with hemophilia.

Dr. Ellis Neufeld, clinical director of hematology at St. Jude Children’s Research Hospital in Memphis, said the recall of Vioxx, while certainly advisable given the safety concerns, robbed patients with hemophilia of an important treatment.

“That was a bad day,” Neufeld said. “We really lamented it. Vioxx was a good drug.”

In the years since, doctors have reached for steroids, physical therapy, and even opioids to treat the pain of hemophilic arthropathy. In severe cases, patients get their problematic joints replaced. But each solution comes with limitations. Steroids can only be used for a short time, and opioids come with serious risks of abuse.

“Vioxx certainly left a void in our arsenal,” said Dr. Catherine Broome, a hematologist at Georgetown University Hospital in Washington, D.C.

While physicians who spoke with STAT have no trouble seeing the medical utility of a Vioxx reboot, the business case is a little less clear.

There are only about 20,000 people in the U.S. with hemophilia, and, thanks to modern treatment, the percentage who develop hemophilic arthropathy has decreased over time, doctors said. Since the 1990s, physicians have been able to replace the missing proteins that prevent clotting in patients with hemophilia, minimizing the number of bleeds and thus reducing the incidence of hemophilic arthropathy.

“If you take what we dealt with in the early years in my career, the people I was taking care of then, they are all severely affected with hemophilic arthropathy,” said Broome, who has been treating hemophilia patients since 1985. “But if you look at young men in their 20s and 30s right now, you can’t tell them apart from you or me.”

On the horizon are one-time gene therapies that promise to free hemophilia patients from regular infusions of clotting protein. The most advanced of those therapies, a treatment for hemophilia A developed by BioMarin, could win FDA approval as early as next year. If its effects prove to last a lifetime, the number of people with hemophilic arthropathy would further wane.

That could mean Tremeau’s reanimated Vioxx would be a niche product at best, and it might explain the company’s delayed development.

In 2017, Tremeau told the Associated Press that it would need to raise $25 million to fund its pivotal trial. That same year, the company said it “gained agreement” with the FDA on the size, duration, and details of that trial. However, Tremeau has raised just $5.2 million since then and is yet to enroll a single patient.

In an email, a Tremeau representative said the company is “in active discussions with the FDA and the hemophilia community” and plans to start the trial some time in 2020. The company declined to answer questions about the cause of its delay and whether it has enough money to complete the study.

Despite the changing dynamics in hemophilia treatment, “hemophilic arthropathy isn’t going away,” said Dr. Christopher Walsh, a hematologist at Mount Sinai Hospital in New York City who has served as a paid adviser to Tremeau.

“There’s a definite need in this community for alternative pain medication that is not addictive,” Walsh said. “And Vioxx — hopefully, if they do the study — would be one of those drugs. But that remains to be seen.”

About the Author

Damian Garde: National Biotech Reporter

Damian covers biotech and writes The Readout newsletter.

[email protected] @damiangarde