In patients stricken with ulcerative colitis for less than five years, AMT-101 was nearly three times more effective in inducing clinical remission than the placebo after eight weeks.
California-based clinical-stage biopharma company Applied Molecular Transport revealed top-line results from its Phase II MARKET trial of its oral investigational drug AMT-101. While mixed, the data indicate that AMT-101 could be a promising early treatment option for moderate-to-severe ulcerative colitis.
The data, shared Wednesday in a conference call, showed that in patients stricken with ulcerative colitis for less than five years, the combination of 3 mg AMT-101 with anti-TNFa adalimumab induced a 43.8% clinical remission rate after eight weeks of treatment. This is nearly three times higher than comparators treated with placebo plus adalimumab, who only reached a 15.4% clinical remission rate. MARKET defined clinical remission as a Mayo endoscopic subscore of 0 or 1, a rectal bleeding subscore of 0 and a stool frequency subscore of 0 or 1.
Adalimumab is most commonly known as the generic version of AbbVie’s Humira, and the results are somewhat disappointing for AMT, as AMT-101 did not out-perform Humira in the trial.
In the overall study cohort, AMT-101 failed to substantially outperform the placebo, with clinical remission rates of 31.8% and 33.3%, respectively. In the subgroup of patients with disease duration of at least five years, clinical remission rate in the AMT-101 arm was 0%, while that for placebo was 50%.
“The rates of clinical remission observed in the subgroup analysis are particularly encouraging since they suggest that earlier treatment of UC in combination can dramatically increase rates of remission over UC monotherapy alone and over previous benchmarks,” Bittoo Kanwar, M.D., chief medical officer of AMT, said during the conference call. Indeed, previous studies have typically only achieved monotherapy remission rates of 15% to 20%.
“These data… serve as an opportunity to optimize patient selection both in future clinical trials as well as in real-life treatment experience,” Kanwar added.
MARKET is a Phase II, double-blinded and placebo-controlled trial that enrolled 51 moderate-to-severe ulcerative colitis patients who had never been treated with biologics before. Patients were randomly assigned to receive 8 weeks of daily doses of either AMT-101 or a corresponding placebo; both arms were also given adalimumab.
Both the active and placebo treatment groups were generally balanced in terms of baseline demographic factors except for disease duration. Patients given AMT’s drug candidate have had ulcerative colitis for an average of 3.9 years, while those on the adalimumab-only arm have lived with the disease for an average of 8.5 years. Looking into this difference revealed the superior efficacy of AMT-101 over placebo for early ulcerative colitis intervention.
AMT-101 also had a good safety and tolerability profile. Of the 30 treatment-related adverse events documented in MARKET, only two were deemed related to the drug, while one was categorized as severe. One patient eventually discontinued treatment due to side effects.
Afflicting millions of people across the globe, ulcerative colitis is a chronic and inflammatory disease of the gastrointestinal tract. Patients with this condition often suffer from diarrhea, rectal bleeding and bloody stools, abdominal pain and unexplained weight loss. Through the company’s proprietary carrier molecule, AMT-101 delivers the anti-inflammatory cytokine IL-10 directly to the site of inflammation but without entering the bloodstream. This action allows AMT-101 to maximize local efficacy while also avoiding many of the side effects that come with systemic therapies.
“Given the results of this trial, and the compelling posthoc analysis, we plan on engaging FDA for potential next steps in development,” Kanwar said.
