RedHill’s RHB-104 hits primary endpoint in Crohn’s phase 3

A phase 3 trial of RedHill Biopharma’s Crohn’s disease asset has met its primary endpoint. The study linked antibiotic cocktail RHB-104 to a higher rate of remission than placebo after 26 weeks, although the difference between the two arms shrunk later in the trial.

RHB-104 is a formulation of the generic antibiotics clarithromycin, rifabutin and clofazimine that is designed to treat Crohn’s disease by wiping out Mycobacterium avium paratuberculosis infection. 

Some studies have linked infection with the bacterium to Crohn’s disease, suggesting antibiotics could induce remission without causing the side effects associated with existing immunomodulating and immunosuppressive agents. But an earlier version of RHB-104 hit the skids following a Pfizer-sponsored phase 3. RedHill picked up the program after Pfizer failed to find evidence of sustained benefit, leading to the initiation of a 331-patient phase 3 intended to set RHB-104 on the path to approval. 

The RedHill trial met its primary endpoint. RedHill linked RHB-104 to a 37% remission rate in the intent-to-treat population after 26 weeks. The rate in the placebo arm was 23%, resulting in the trial hitting its primary endpoint with a p value of 0.013. RedHill also reported statistically significant differences in remission at week 16 and in response at week 26.

Pfizer’s phase 3 also reported a statistically significant difference in remission rates at week 16, but the gap closed over the course of the three-year trial. A subsequent reanalysis painted the long-term efficacy of drug in a better light but Pfizer dropped the program nonetheless.

RedHill sought to learn from the disputed aspects of Pfizer’s study, leading it to reformulate the drug and choose remission as its primary endpoint. The long-term efficacy of RHD-104 remains an issue, though.

By the 52-week point of RedHill’s phase 3, the difference in the remission rates of the RHD-104 and placebo groups had fallen to seven percentage points. That resulted in a p value of 0.155. Pfizer’s trial saw a similar tailing off of the efficacy of the antibiotics at 52, 104 and 156 weeks. But the subsequent reanalysis found statistical significant differences persisted at 52 and 104 weeks with p values of 0.003 and 0.005, respectively. 

RedHill expects the need to run additional clinical trials before filing for approval of RHD-104 and is now preparing to figure out the next steps together.

"We continue to analyze the study data and plan to meet with key opinion leaders and the FDA to present the data package and discuss the development path to potential approval of RHB-104," Ira Kalfus, M.D., RedHill’s medical director, said in a statement.

RedHill will need to persuade investors to bankroll the next steps in the program. Having burned through $9.5 million in the preceding three months, RedHill closed out the first quarter with $36 million in cash.

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