Protagonist Forges Ahead with UC Drug On Strength of Low Dose Data

Clinical Trial Concept

Protagonist Therapeutics' Phase II study in moderate-to-severe ulcerative colitis failed to meet its primary endpoint at a higher dosage amount. Even so, the company remains optimistic about the drug's future.

Sharing top-line results from the Ideal trial on PN-943 for patients diagnosed with UC, Protagonist said that while the primary endpoint was missed in the group who received 450 mg twice daily, the group who received 150 mg had 13% better remission outcomes than the placebo. The participants who received the lower dose also achieved 16% better outcomes and demonstrated strong concordance across various parameters, including statistically significant histological remission and endoscopic improvement.

The Ideal study concluded in April 2022 and covered 159 patients with moderate-to-severe active UC. It was designed to assess the efficacy and safety of PN-943, an oral, gut-restricted, alpha-4-beta-7-integrin antagonist. The candidates are dosed either twice daily with 150 mg, 450 mg or a placebo over a 12-week period.

Despite its failure to meet the primary endpoint at the 450 mg dose, Protagonist is moving forward to a Phase III registrational trial. This is due to the positive outcomes from the 150 mg group and the fact that there is a significant unmet need for therapy of its kind.

"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. 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 III registrational program," Scott Plevy, M.D., executive vice president and therapeutic head of gastroenterology at Protagonist said in a statement.

Bruce Sands, M.D., the principal investigator for the trial and professor of medicine at the Icahn School of Medicine at Mount Sinai, reinforced the company's decision to proceed to Phase III, noting that PN-943 offers a strong potential benefit for people with ulcerative colitis.

"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 III registrational study," Sands said.

Plans for the Phase III trial are underway, and Protagonist plans to focus on ulcerative colitis, though the indication could extend to other diseases down the line.

"Based on its convenience of oral administration and the favorable efficacy and safety results observed to date, we believe that PN-943 has the potential to become a first-in-class, foundational oral medicine for individuals living with moderate-to-severe ulcerative colitis," Protagonist president and CEO Dinesh V. Patel added.

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