Tremeau Pharmaceuticals has received guidance from the U.S. Food and Drug Administration (FDA) on how to conduct a pivotal Phase 3 trial exploring rofecoxib (TRM-201) in patients with hemophilia-associated joint pain.
The advice was offered during a formal meeting with the agency, where both parties agreed on the design of the study, improving the potential to get the drug approved if study findings are positive.
“Aligning with the FDA on the [Phase 3] program size, duration, and dosing as well as the pharmacokinetic requirements is a major step forward for patients with HA [hemophilic arthropathy] and Tremeau,” Mark H.N. Corrigan, MD, president of research and development for Tremeau, said in a press release.
Recurrent bleeding into the joints causes damage and pain in hemophilia patients. While non-steroid anti-inflammatory drugs (NSAIDs) are among the most common pain medications for other people, patients with hemophilia cannot take such drugs because they increase bleeding risk by preventing platelet aggregation. Instead, joint pain usually is treated with high-potency opioids.
While rofecoxib is an NSAID, it belongs to the group of selective NSAIDS, targeting only one of the two COX enzymes involved in pain. Since only one of the enzymes (COX1) is involved in platelet aggregation, rofecoxib, which targets COX2, is safer to use in hemophilia patients.
The FDA recently granted the medication an orphan drug designation for use in hemophilia joint pain.
“The significant unmet medical need, and the known efficacy profile of rofecoxib enabled alignment on a streamlined program, including a single [Phase 3] study, that, if successful, will inform the safe and effective use in the HA patient population,” said Corrigan.
“Combined with our recently approved orphan drug designation for the treatment of HA, gaining agreement with and guidance from FDA on an efficient development program for rofecoxib is an important milestone,” added Bradford C. Sippy, Tremeau’s CEO.
Rofecoxib was initially developed to overcome the safety issues of traditional NSAIDs, including the increased bleeding risk and high risk of gastric bleeding. In 1999 the FDA approved the treatment, under the brand name Vioxx, for chronic pain in patients with arthritis and a number of other pain conditions.
Following approval, it became clear that patients taking rofecoxib had an increased risk of heart attacks, and its developer, Merck, voluntarily withdrew it from the market in 2004.
Nevertheless, the FDA agrees with Tremeau that the drug can be beneficial in select patients with hemophilia joint pain, where its risk-benefit profile is considered good. Patients who have had a coronary artery bypass will not be able to take the medication, if approved.
“We look forward to initiating our [Phase 3] study for rofecoxib and bringing forth a viable alternative to opioids for patients with HA,” said Sippy.