Findings from the Phase II ARTEMIS-UC and Phase IIa APOLLO-CD trials show that Prometheus’ PRA023 is potentially safe and effective for treating ulcerative colitis and Crohn’s disease.
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Findings from Prometheus Biosciences’ Phase II ARTEMIS-UC and Phase IIa APOLLO-CD trials show that PRA023, an anti-TL1A monoclonal antibody, is potentially safe and effective in ulcerative colitis and Crohn’s disease.
With these promising data, the California biotech will engage key regulatory bodies to advance the candidate into pivotal development next year. The full data sets and analyses will be presented at an upcoming medical meeting.
In response to PRA023’s performance, Prometheus stocks surged more than 190%.
In an investor call held Wednesday morning, Mark McKenna, chairman and CEO of Prometheus, said that the company will “take the next several months to refine our registrational plans” and collect feedback for regulatory applications for PRA023.
“Given these impressive results at hand, we expect to have a number of attractive options to finance our registrational studies” for PRA023, he added. The data will also empower Prometheus to explore other indications for the candidate and continue to advance its precision-guided approach to inflammatory bowel diseases.
“We believe these data clearly validate the Prometheus platform and our pipeline and sets us up for future leadership” in this therapeutic space, McKenna said.
ARTEMIS-UC was a double-blinded and placebo-controlled trial that enrolled patients with moderately-to-severely active ulcerative colitis who had failed a previous line of therapy. 26.5% of patients treated with PRA023 met the primary efficacy endpoint of clinical remission, as per the Mayo score, as opposed to only 1.5% of the placebo group.
Prometheus’ candidate also induced statistically higher rates of endoscopic improvement, the study’s secondary endpoint, with a placebo-adjusted rate of 30.8% in favor of PRA023.
In APOLLO-CD, 55 patients with moderately-to-severely active Crohn’s disease were enrolled, all of whom had previously failed biologic or conventional therapies. Treatment with PRA023 led to an endoscopic response in 26.0% of patients, statistically better than a historical placebo rate of 12%.
Clinical remission was also significantly higher than PRA023, at 49.1%, as opposed to 16% in prespecified historical controls.
Aside from clinical metrics, Crohn’s disease patients treated with PRA023 saw a sharp reduction in biomarkers of inflammation and expression of disease-related genes.
In both APOLLO-CD and ARTEMIS-UC, PRA023 showed a favorable tolerability profile, inducing no treatment-emergent serious adverse events or toxicities leading to treatment discontinuations.
Bringing a Precision Approach to Inflammatory Bowel Diseases
With PRA023, Prometheus seeks to bring a precision treatment approach, most commonly applied in oncology indications, to immune-mediated and inflammatory diseases.
The candidate is an IgG1 humanized monoclonal antibody that blocks the action of the tumor necrosis factor-like ligand 1A. This target is a biomarker commonly associated with intestinal inflammation and fibrosis.
To go with PRA023, the company is also developing companion diagnostic products to identify patients most likely to respond to treatment. These diagnostic algorithms likewise performed well in both APOLLO-CD and ARTEMIS-UC. Prometheus will also advance these companion diagnostics into registrational studies.
Aside from Crohn’s disease and ulcerative colitis, PRA023 is also being assessed for systemic sclerosis-associated interstitial lung disease.
