September 29, 2020
BIOINVEST NEWS: Myovant (MYOV)
Regugolix HERO Data Equivalent But Not Superior to Leuprolide in Castration Resistance-Free Survival, Remains on Track For Approval With Dec. 20 PDUFA
MYOV announced results of an additional secondary endpoint from the Phase III HERO study evaluating relugolix in men with advanced prostate cancer. Relugolix did not achieve statistical superiority for castration resistance-free survival compared to leuprolide acetate in men with metastatic disease through 48 weeks. In the subgroup of men with metastatic disease treated with relugolix, 74% were castration-resistance free (CRFS) through 48 weeks compared to 75% men treated with leuprolide acetate (HR = 1.03 [95% CI: 0.68-1.57]; p = 0.84). The Street is disappointed that CRFS was only equivalent and not superior to leuprolide. In our view, this is an overreaction as we expect the drug to be approved by it’s PDUFA date of December 20th based on the fact that regugolix hit the primary endpoint with 96.7% of men treated with relugolix achieving sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks versus 88.8% of men treated with leuprolide acetate.
Although survival was equivalent, HERO showed that men in the relugolix group had a 54% lower risk of major adverse cardiovascular events (MACE) compared to men in the leuprolide acetate group (2.9% vs. 6.2%, respectively). In men with a reported history of MACE, the relugolix group had 80% fewer MACE events reported compared to the leuprolide acetate group (3.6% vs. 17.8%, respectively). The overall incidence of adverse events in the relugolix and leuprolide acetate groups was comparable (92.9% vs. 93.5%, respectively) but in our view the reduction in CV events bodes well for future market market share gains.
In our view, failure to deliver superiority in a secondary endpoint, CRFS, will not affect the upcoming relugolix PDUFA. Relugolix (120 mg) is under Priority Review by the FDA for the treatment of men with advanced prostate cancer, with a target action date of December 20, 2020. We expect the FDA to base their review on the Phase III HERO study, relugolix met the primary efficacy endpoint, with 96.7% of men treated with relugolix achieving sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks versus 88.8% of men treated with leuprolide acetate. The potential inclusion of the reduced cardiovascular risk in the label will also help show differentiation. We expect the drug to be approved by or before it’s PDUFA based on HERO’s initial safety and efficacy results, along with its oral dosing profile which combine to make regugolix the best-in-class. We recommend subscribers to add to positions on what believe is an oversold reaction.