The investigators will now move forward testing the 150 mg dosage of the treatment in a phase 3 trial.
New topline data shows PN-943 is effective in treating patients with moderate-to-severe ulcerative colitis.
Protagonist Therapeutics announced the new results from the IDEAL study, a randomized, double-blinded, placebo-controlled, multicenter phase 2 trial evaluating the safety and efficacy of PN-943, an oral, gut-restricted, alpha-4-beta-7-intergrin antagonist. The study included 159 patients with moderate-to-severely active ulcerative colitis.
"The oral, gut-restricted agent PN-943 appears to exert similar effects at the twice daily 150 mg dose in comparison to the approved injectable alpha-4-beta-7-integrin antibody drug and its mechanism of action," said Bruce Sands, MD, MS, the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, principal investigator for the IDEAL study and consultant to Protagonist, in a statement. "There is a clear unmet need and strong clinical benefit for patients with an oral agent working through such a proven IBD specific mechanism, and the IDEAL study results provide good rationale for moving PN-943 forward in a Phase 3 registrational study."
Each participant was randomized to receive either twice daily BID with 450 mg or 150 mg PN-943 or placebo for 12 weeks.
The results show patients treated with the 450 mg BID dose did not meet the prespecified primary endpoint, but the 150 mg dosage did achieve a placebo versus treatment delta of 13% (P = 0.08) in the modified intent to treat group. There was also a delta of 16% (P = 0.04) in the bio-naïve group.
Overall, PN-943 150 mg BID resulted in a 27.5% clinical remission rate, compared to 14.5% for the placebo group (delta 13%, P = 0.08).
The investigators also found a strong concordance across different parameters in the 150 mg BID data, including statistically significant histological remission and endoscopic improvement.
For safety, the adverse event rate was similar between the 150 mg BID dose group and the placebo cohort.
The team now plans on moving forward with a phase 3 program testing the safety and efficacy of PN-943 150 mg BID dosing.
"With the IDEAL study, we have demonstrated clinical proof-of-concept and validation for potential treatment of ulcerative colitis via oral, gut-restricted blockade of the alpha-4-beta-7-integrin pathway," said Scott Plevy, MD, Executive Vice President and Therapeutic Head of Gastroenterology at Protagonist, in a statement. “The dose response demonstrated by this study is consistent with several other modalities in the integrin pathway. The findings in the lower-dose arm provide consistent evidence of clinical efficacy and safety, and clear direction on the dosing regimen for the Phase 3 registrational program."