Recursion plans to begin a registrational trial of REC-4881 in the second half of 2027, following positive mid-stage results for the oral drug in familial adenomatous polyposis (FAP). The company said the timing is subject to discussions with the FDA and that it expects to provide further details later this year.
Updated findings from the Phase Ib/II TUPELO trial showed that 13 of 15 patients had a reduction in total polyp burden after 12 weeks of treatment, with a median reduction of 47%. About one-third of patients saw reductions of at least 65%. The data were presented by Mayo Clinic gastroenterologist Lisa Boardman at the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer annual meeting in Denver.
The study assessed REC-4881 at 4 mg once daily for 12 weeks, followed by 12 weeks off treatment. At Week 25, 11 of 13 patients remained below their baseline total polyp burden. Recursion said that reductions persisted in most patients during the period off treatment, which could allow flexibility in dosing.
Results varied by part of the gastrointestinal tract. In the upper GI tract, 12 of 13 patients had lower polyp burden after treatment, with a median reduction of 55%; 11 of 12 remained below baseline at Week 25. In the lower GI tract, nine of 11 patients with measurable polyps at baseline improved, with a median reduction of 50%, and seven of 10 remained below baseline after the off-treatment period.
Among eight patients with polyps larger than 5 mm at baseline, six had fewer such polyps after 12 weeks. Two patients saw counts fall from more than 90 to one. The largest reported response was a 98% reduction in total polyp burden, from 1,344 mm to 32 mm. Recursion cautioned that this patient was not representative of the overall study population. The trial also did not record separate counts for polyps larger than 10 mm.
No new safety signals were reported in the expanded patient group. Most treatment-related adverse events were Grade 1 or 2; four patients had Grade 3 events, and none had Grade 4 or 5 events. The most common events included acneiform dermatitis, rash, increased CPK, diarrhea and an asymptomatic decrease in left ventricular ejection fraction. Four patients stopped treatment because of Grade 1 or 2 events; no one discontinued due to a Grade 3 event.
REC-4881 is an oral inhibitor of MEK1 and MEK2 that Recursion is developing under a global licensing agreement with Takeda, signed in 2020. FAP is a rare inherited disorder for which care has traditionally involved ongoing endoscopic surveillance and, in many cases, preventive removal of the colon. Recursion says there are no FDA-approved drug therapies for the condition.