Bridge Biotherapeutics is keeping the faith after seeing its lead inflammation candidate fail a midphase trial. BBT-401 performed numerically worse than placebo in the ulcerative colitis clinical trial, but Bridge continues to see the Pellino-1 inhibitor as an important asset and is plotting formulation changes.
The drug candidate is designed to stay in the gastrointestinal tract, rather than be absorbed into the blood, and thereby selectively suppress inflammation in the large intestine without causing systemic side effects. By binding to Pellino-1, BBT-401 could block the transmission of the inflammatory signals that contribute to ulcerative colitis.
Bridge is yet to validate that idea in the clinic. The Korean biotech, after fronting up about the failure to hit the efficacy endpoint, noted that 54.5% of the treatment cohort exhibited a valid treatment response to orally administered BBT-401. The problem? The response rate in the placebo arm was 63.6%.
The primary efficacy endpoint defined clinical response as a reduction of three points or more, and an improvement of 30% or more, from baseline on the Mayo score that is used in many ulcerative colitis trials. The highest response rate, 63.6%, was seen in patients who received placebo twice a day for 57 days. The response rate in the once- and twice-daily BBT-401 cohorts was 54.5%.
BBT-401 failed to beat placebo despite Bridge’s work to improve the candidate. After reviewing data from an earlier phase 2a trial of a lower dose, the biotech developed a new formulation to improve drug delivery to the colon and ileum. Bridge said the changes improved drug distribution, but that failed to translate into efficacy.
Even so, Bridge thinks it’s on the right track. James Lee, founder and CEO of Bridge, outlined plans to “further improve the delivery of the drug and the treatment efficacy” in a statement that reaffirmed the company’s belief in BBT-401.
“We remain committed to the development of BBT-401,” the CEO said. “We believe this first-in-class Pellino-1 inhibitor remains an important candidate to address unmet medical needs in the treatment of ulcerative colitis. We are also encouraged by the safety and tolerability results of the study.”