Oric Pharmaceuticals has picked the phase 3 dose for its prostate cancer prospect, barreling into the pivotal program while outlining a claimed edge over Pfizer’s rival candidate. But investors sent the stock down as they digested Oric’s phase 1b data and choice of pivotal treatment regimen.
The phase 3 trial, which will start in the first half of the year, will test 400-mg, once-daily doses of Oric’s PRC2 inhibitor rinzimetostat in combination with Bayer’s Nubeqa in metastatic castration-resistant prostate cancer patients previously treated with abiraterone. At an interim phase 1b analysis, 33% of patients on the regimen had at least a 50% decline in prostate-specific antigen (PSA). Oric reported a 40% rate of PSA50 across all doses in November.
California-based Oric posted an 84% radiographic progression-free survival (rPFS) rate after five months. The company said the rPFS results were consistent with Pfizer’s rival EZH2 inhibitor, mevrometostat, and better than standard-of-care therapies including Novartis’ Pluvicto.
On a call with investors to discuss the results, Oric Chief Medical Officer Pratik Multani, M.D., said the biotech chose 400 mg, not 600 mg, for the phase 3 dose after seeing no statistical relationship between exposure and efficacy. The 400-mg dose performed numerically better than the 600-mg dose on some measures, Multani said, and the confidence intervals overlapped.
While the efficacy data suggested the doses are comparable, the safety and tolerability results pointed to a clear advantage for 400 mg. Oric saw more toxicity and dose modifications at the 600-mg dose, leading it to advance the lower dose into phase 3. Citi analysts called the choice of dose “logical” in a note to investors.
Safety and tolerability are key to Oric’s plans. Pfizer has taken mevrometostat into phase 3 based on data that suggest it matches rinzimetostat’s efficacy. Lagging behind its rival, Oric sees mevrometostat’s rates of gastrointestinal and hematological adverse events, plus cases of dysgeusia and alopecia, as areas to gain an edge. Oric CEO Jacob Chacko told investors rinzimetostat’s safety profile “looks markedly better.”
Another analyst asked about Nubeqa's selection as a phase 3 combination drug. Oric also studied its candidate with Johnson & Johnson’s Erleada. Like Nubeqa, Erleada is an androgen receptor inhibitor. Chacko said Oric chose Nubeqa to avoid the drug-drug interactions associated with Erleada, adding that the company could combine rinzimetostat with J&J’s product in future phase 3 studies.
Oric shares were trading down 24% to $9.60 in the first hour of trading Wednesday compared to a Tuesday closing price of $12.67. Citi analysts said the stock drop could reflect confusion about the choice of the 400-mg dose or “possibly misguided expectations of greater efficacy” compared to mevrometostat.
While Pfizer’s candidate is leading the race, the analysts said the safety data support Oric’s belief that rinzimetostat can claim a substantial share of the post-abiraterone market.
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