Ritter Pharmaceuticals has posted phase 2b/3 lactose intolerance data it claims set it up to run a confirmatory late-stage study and file for approval. But the trial missed its primary endpoint, with Ritter only able to make the figures hit statistical significance by removing 20% of patients from its analysis.
Los Angeles, CA-based Ritter enrolled 377 patients with lactose intolerance and randomized them to receive one of two doses of RP-G28—a galactooligosaccharide prebiotic—or placebo. Among the 368 patients who received at least one dose of the drug, RP-G28 failed to outperform placebo in terms of improving abdominal symptoms to the extent that statistical significance was achieved. This meant the trial missed its primary endpoint.
However, Ritter reported the study met its primary objective when the 72 patients enrolled at one site were excluded. Ritter removed these patients from its analysis after identifying “significant irregularities” at the site.
In the analysis of the remaining 296 patients, the response rate across the RP-G28 arms was 40%, the same as was achieved in the full, 368-patient trial. What changed by stripping the 72 subjects from the analysis was the placebo response rate. In the original analysis, a placebo response rate of 31% resulted in the trial missing its primary endpoint. When the 72 patients were removed, this fell to 26%, resulting in the study hitting its primary endpoint.
Ritter changed the primary endpoint of the trial earlier this month, five months after it completed the study. The company said it moved to the new endpoint—which combines the originally-used abdominal pain measure with secondary data on cramping, bloating and gas—while the trial was still blinded and after discussing the idea with FDA. Ritter spoke to FDA to increase the chances of the agency seeing the study as pivotal.
“The responder composite score instrument, which we worked with the FDA to establish, performed as anticipated to best quantify and evaluate clinically meaningful treatment benefit for lactose intolerance sufferers,” University of California San Diego’s William Sandborn, M.D. said in a statement. “I believe the totality of the results and the multitude of positive outcome measures demonstrates there is a clear treatment benefit for subjects taking RP-G28.”
Ritter thinks the data are strong enough to tee it up to run a confirmatory phase 3 program and then file for approval. The company has requested an end-of-phase 2 meeting with FDA to get the agency’s take on the data and the path forward.
Any significant further development of RP-G28 will strain Ritter’s current cash reserves. The firm closed out last year with $7 million in cash, a sum that represents what it has left from its $20 million IPO in 2015 and subsequent financings.
Shares in nano-cap Ritter initially fell in after hours trading, but rebounded to close up 15%.