One day after announcing positive Phase II results from separate trials for ulcerative colitis and Crohn’s disease, Prometheus Biosciences announced pricing of a public stock offering intended to net $500 million for the company to fund Phase III clinical studies for both.
The company’s therapeutic candidate, PRA023 is an IgG1 humanized monoclonal antibody that has been shown to block tumor necrosis factor (TNF)-like ligand 1A (TL1A). The drug candidate has shown the potential via the Phase II ARTEMIS-UC study to substantially improve outcomes for moderate-to-severely active ulcerative colitis (UC) who have failed conventional or advanced therapy; and a concurrent Phase IIa study named APOLLO-CD demonstrating equally encouraging results in Crohn’s disease (CD).
Ulcerative colitis trial
ARTEMIS-UC was a 12-week, double-blind, placebo-controlled, randomized study of PRA023 for UC that met the primary and all ranked secondary endpoints including clinical, endoscopic, histologic, and patient-reported outcome measures in the initial cohort (Cohort 1) of the trial. All 68 of the PRA023-treated patients completed the Cohort 1 study, compared to 60 of 67 in the placebo group. Result showed that 26.5% of patients receiving PRA023 reached the primary endpoint of clinical remission compared with 1.5% on placebo, for a placebo-adjusted clinical remission rate of 25.0% on the primary endpoint. A secondary endpoint of endoscopic improvement was reached by 36.8% of patients on PRA023 compared with 6.0% on placebo, for a placebo-adjusted endoscopic improvement rate of 30.8% on the secondary endpoint. The study had
PRA023 was well tolerated in Cohort 1, with no treatment-emergent serious adverse events (SAEs), adverse events (AEs) leading to discontinuation. The only AE that occurred in more than two patients and at a higher frequency in the PRA023 group compared to placebo was COVID-19 in five of the 68 patients receiving PRA023 and in three of 67 patients on placebo.
Crohn’s disease trial
The APOLLO-CD clinical trial was a 12-week open-label study that enrolled 55 patients with moderate-to-severely active Crohn’s disease (CD) with endoscopically active disease who had failed conventional or biologic therapy. The study enrolled a highly refractory patient population with 70.9% of patients previously treated with at least one biologic therapy and 52.7% treated with two or more biologic therapies. Result showed that:
- 0% of patients on PRA023 achieved endoscopic response (p=0.002 compared to 12% prespecified historical placebo rate)
- 1% of patients on PRA023 achieved clinical remission (p<0.001 compared to 16% prespecified historical placebo rate)
As in the ARTEMIS-UC study, PRA023 showed no treatment-emergent SAEs, or adverse events AEs leading to discontinuation, or severe AEs assessed as related to PRA023 by the investigator. AEs that occurred in more than two patients included COVID-19, urinary tract infection, CD, anemia, nasopharyngitis and fatigue.
Companion diagnostic evaluation
In conjunction with both trials, Prometheus also conducted companion diagnostic (CDx) evaluations for each indication. In the ARTEMIS-UC study, the interim CDx evaluation, from limited patient numbers (N32), showed a placebo-adjusted clinical remission rate of 37.5%, compared with the placebo-adjusted remission rate of 25.0% for all-comers. And expansion cohort (Cohort 2) to further assess treatment efficacy in UC patients is continuing to enroll with results expected the middle of next year.
In the APOLLO-CD study, Prometheus sought to validate prespecified biomarkers to predict response employing its Crohn’s-specific algorithm. Results showed a predictive power of 45.0% (9/20) endoscopic response relative to all-comers of 26% (13/50). While the original algorithm provided limited benefit on some of the endpoints, the alternative algorithm demonstrated enhanced performance across both clinical and endoscopic outcomes. As a result, Prometheus will push forward its alternative algorithm for further studies.
“We are beyond enthusiastic with these study results and what they could mean for patients suffering from IBD,” said Mark McKenna, chairman and CEO of Prometheus. “The performance of PRA023 in both UC and Crohn’s patients has surpassed our expectations. We believe PRA023 and our precision medicine approach has the potential to change the paradigm of IBD treatment and we look forward to discussions with regulatory agencies as we prepare to advance into Phase III studies in Ulcerative Colitis and Crohn’s Disease.”