TRM-201 (rofecoxib) for hemophilia

Last updated Feb. 13, 2024, by Margarida Maia, PhD
Fact-checked by Joana Carvalho, PhD

What is TRM-201 for hemophilia?

TRM-201 (rofecoxib) is an oral nonsteroidal anti-inflammatory drug (NSAID) being developed by Tremeau Pharmaceuticals to treat hemophilic arthropathy, a degenerative joint disease that can occur due to recurrent joint bleeds in people with hemophilia.

The medication was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in November 2017 for treating hemophilic arthropathy.

Rofecoxib was marketed by Merck under the name Vioxx until it was voluntarily recalled from the market in September 2004 over safety concerns that it could increase the risk of heart attack and stroke when taken for a long time. Vioxx was approved for easing the signs and symptoms of arthritis, managing acute pain, easing menstrual pain, or treating migraines in adults.

It has since been understood that all NSAIDS carry a risk of cardiovascular events and gastrointestinal bleeding that depends on the dose and duration of use. For this reason, the FDA requires that labels include a boxed warning that detail these risks.

Therapy snapshot

How does TRM-201 work in hemophilia?

Hemophilia occurs when blood fails to clot properly due to the lack or dysfunction of a specific clotting protein. As a result, people with hemophilia experience heavy, longer-than-usual bleeding episodes that can happen spontaneously without an apparent reason or after an injury or trauma.

Bleeding into the joints can cause them to swell, limiting their movement. When bleeding occurs repeatedly, it can lead to a complication called hemophilic arthropathy, which is marked by permanent and irreversible joint damage, pain, and a limited range of motion.

TRM-201 contains rofecoxib, a NSAID that inhibits COX-2, a cyclooxygenase (COX) enzyme that helps the body make prostaglandins, which are chemicals that promote pain and inflammation. Inhibiting COX-2 should help relieve joint pain and improve physical function in people with hemophilic arthropathy. Contrary to traditional NSAIDs, which inhibit another COX enzyme called COX-1, rofecoxib isn’t expected to upset the stomach or increase the risk of gastrointestinal bleeding.

In a meeting with Tremeau, the FDA agreed its patented formulation of 17.5 mg of rofecoxib reached levels similar to Vioxx’s 25 mg of rofecoxib.

How will TRM-201 be administered in hemophilia?

In clinical testing, TRM-201 has been given as a once daily oral tablet containing 17.5 mg of rofecoxib.

TRM-201 in hemophilia clinical trials

A Phase 3 clinical trial, called RESET-HA (NCT04684511), was launched in 2021 to test the safety and effectiveness of TRM-201 in adults and adolescents, ages 12-75, who’d been diagnosed with hemophilic arthropathy due to hemophilia A or B. The study was stopped due to low enrollment in 2022.

As part of the clinical trial, patients would have been randomly assigned to receive a once daily oral tablet of either TRM-201 or a placebo for 12 weeks (about three months). The company expected to enroll up to 80 patients in each group. Those who completed the 12 weeks of treatment would have been able to roll over into a yearlong extension where everyone would have been given TRM-201.

The main goal of RESET-HA was to watch for changes in joint pain, measured on a numeric rating scale from 0 (no pain) to 10 (the most severe pain), over 12 weeks.

Common side effects of TRM-201

There have been no reports of side effects associated with TRM-201 to date.

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