Recently, Myovant Sciences announced the additional results of the once-daily oral drug relugolix in the treatment of advanced prostate cancer stage III HERO study (NCT03085095). These data extend the early findings of the HERO study and confirm that relugolix shows superiority at multiple endpoints compared to leuprolide acetate and has a lower risk of major adverse cardiovascular events (MACE). The results were reported orally at ASCO in 2020 and published simultaneously in the New England Journal of Medicine (NEJM).
HERO is a randomized, open-label, parallel group, multi-country phase III study designed to evaluate the safety and effectiveness of relugolix in male patients with androgen-sensitive advanced prostate cancer who require at least one year of continuous androgen deprivation therapy (ADT) Sex. In the study, patients were randomly assigned in a 2:1 ratio, receiving a single oral dose of 360 mg loading of relugolix, followed by a daily oral dose of 120 mg, or receiving leuprolide acetate suspension suspension (once in March). .
The results showed that relugolix reached the primary endpoint and showed superiority to leuprolide acetate at 6 key secondary endpoints. In the primary endpoint responder analysis, 96.7% of patients in the relugolix group achieved sustained testosterone suppression at the castration level (<50ng/dL) during 48 weeks of treatment, compared with 88.8% in the leuprolide acetate group.
The detailed secondary endpoint data released this time showed that there were significant differences in the rapid and deep suppression of testosterone, PSA response, and testosterone recovery after treatment was stopped. The proportion of patients who reached the castration level on the 4th day of treatment in the Relugolix group was 56.0% and increased to 98.7% on the 15th day. The leuprolide acetate group had 0.0% on the 4th day and 12.1% on the 15th day. In addition, 78.4% of men in the relugolix group achieved deep testosterone suppression below 20 ng/dL on day 15, compared with 1.0% in the leuprolide acetate group. A higher percentage of patients in the Relugolix group achieved a PSA response on day 15 (PSA level reduction >50%) and were confirmed on day 29 (79.4% vs 19.8%). After 90 days of discontinuation of treatment, 54% of patients in the relugolix group achieved normal testosterone levels (≥280ng/dL) and an average testosterone level of 288.4ng/dL. The proportion of leuprolide acetate group was only 3% and the average testosterone level was 58.6 %. Another key secondary endpoint of the study is the castration-free resistance survival period, and results are expected in the third quarter of this year.
In terms of safety, the risk of MACE in the relugolix group was reduced by 54% (2.9% vs 6.2%; HR=0.46; 95%CI: 0.24-088).
In addition, among patients with a history of MACE events, the risk of MACE in the relugolix group was reduced by 80% (3.6% vs 17.8%). In the HERO study, more than 90% of patients had at least one cardiovascular risk factor, including lifestyle risk factors such as smoking and obesity, comorbidities such as diabetes and hypertension, and a previous history of MACE.
As mentioned earlier, the incidence of adverse events in the HERO study was comparable between the relugolix group and the leuprolide acetate group (92.9% vs 93.5%). The most frequently reported adverse events that occurred in at least 10% of men in the relugolix group were hot flashes, fatigue, constipation, mild to moderate diarrhea, and joint pain.
In patients with prostate cancer, lowering testosterone levels more quickly and recovering testosterone levels more quickly after stopping treatment are of clinical importance, which can potentially improve the quality of life of patients. Both findings will have a meaningful impact on the treatment of patients with advanced prostate cancer. In addition, cardiovascular disease is the leading cause of death in patients with prostate cancer. Compared with conventional GnRH agonist drugs, oral therapy has a strong effect and also reduces the risk of cardiovascular disease, which will be a major achievement for male patients with advanced prostate cancer.
Based on the above results, relugolix has the potential to become an important new treatment option for male patients with advanced prostate cancer, and will redefine the clinical care of patients. In April of this year, Myovant submitted a New Drug Application (NDA) to the US FDA. If approved, relugolix will be the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist drug used to treat patients with advanced prostate cancer.
Currently, Myovant is developing relugolix as a single tablet for the treatment of advanced prostate cancer (120 mg daily), and is also developing a relugolix compound tablet (relugolix 40 mg/estradiol 1.0 mg/norethisterone acetate 0.5 mg) , Used to treat uterine fibroids and endometrial cancer. Last month, the company reported the positive results of the first phase III clinical study of endometriosis, and another phase III study is expected to be announced later this quarter.