Our HERO trial is a phase III multinational randomised open label parallel group study to evaluate the safety and efficacy of relugolix in men with advanced prostate cancer. The primary endpoint was sustained castration through a 48 week period. 934 men were randomised 2-to-1 to receive relugolix, a 120mg oral GnRH antagonist daily, versus leuprolide 22.5mg every three months. The oral once a day pill had a one day loading dose of 360mg.
T suppression through 48 weeks was our primary endpoint, we had numerous secondary endpoints looking at profound castration levels, typically regarded as a testosterone level of 2ng/dL or less and with corollary PSA findings. Additionally, we looked at a subset of patients for T recovery in both arms, 184 of the 934.
Of course we looked at adverse event profile and we had a pre-specified analysis for patients for major adverse cardiovascular events. Just as an overview, relugolix is a GnRH antagonist as opposed to an LHRH agonist so you don’t get the well described supraphysiologic surge of LH, FSH and testosterone but you get the rather immediate decline in testosterone. So what we saw was a marked decline at day 4 and day 15 with profound castration levels as well, in contradistinction to the leuprolide arm.
Then ultimately what we found was not only did we meet our primary endpoint of non-inferiority where we had a 96.7% T suppression in the relugolix arm and 88.8% T suppression in the leuprolide arm. Because of this we were able to also look at the between group difference and as long as it was less than the -10% non-inferior margin, which it was, it was 7.9%, we thus could claim superiority in addition to non-inferiority regarding T suppression.
As it relates to the subgroup or the subset of 184 patients who stopped treatment at the end of 48 weeks in both arms, 54% of patients in the relugolix arm achieved normal testosterone levels by 90 days whereas only 3% did so in the leuprolide arm.
Finally, in addition to the daily pill convenience, the T suppression, the T recovery, we looked at cardiovascular events and there was a finding of 6.2% of patients in the leuprolide arm attained major adverse cardiovascular events as opposed to 2.9% in the relugolix arm. That’s described as a MACE and these are non-fatal myocardial infarction, non-fatal stroke plus all-cause mortality. The Kaplan-Meier curve which we demonstrated showed a 54% reduction in the risk of MACE for the relugolix versus the leuprolide arm and this curve separated very, very early in the trial. We’re really proud to have published our findings in The New England Journal of Medicine simultaneously with our virtual ASCO presentation.
I really would be remiss if I didn’t thank all of my co-investigators and my co-authors for achieving the success of the study. We look forward to submitting relugolix for regulatory evaluation and potential approval. Thank you.