A New Drug Application has been submitted to the FDA for single-agent relugolix for use as a treatment for men with advanced prostate cancer.
A New Drug Application (NDA) has been submitted to the FDA for single-agent relugolix for use as a treatment for men with advanced prostate cancer, according to Myovant Sciences, the developer of the oral GnRH receptor antagonist.1
The NDA is based on data from the phase 3 HERO study, which compared relugolix to leuprolide acetate. The results showed that 96.7% (95% CI, 94.9-97.9) of men receiving once-daily, oral relugolix achieved sustained testosterone suppression to castrate levels (≤50 ng/dL) through 48 weeks.2
“The submission of our NDA for prostate cancer is a major step towards providing a 1 pill, once a day potential new treatment option for men with advanced prostate cancer,” Lynn Seely, MD, chief executive officer of Myovant Sciences, said in a press release. “Based on the robust efficacy and safety data from the Phase 3 HERO study, we believe relugolix, if approved, could provide men an important oral alternative to leuprolide injections, the current standard of care.”
In the international, open-label, parallel-group, phase III HERO trial (NCT03085095), patients with androgen-sensitive advanced prostate cancer who required ≥1 year of continuous androgen deprivation therapy (ADT) were randomized 2:1 to receive a single loading dose of relugolix at 360 mg followed by relugolix at 120 mg once daily, or leuprolide acetate 3-month depot injection.
The trial, which is still recruiting, is planning to enroll 1100 patients, including those with metastatic prostate cancer that will support an analysis of castration resistance—free survival (n = 430), and Chinese patients that will support registration in China (n = 138).
To be eligible for enrollment, patients must have histologically or cytologically confirmed prostate cancer and is a candidate for ≥1 year of ADT, has a serum testosterone of ≥150 ng/dL at time of screening, has a serum prostate-specific antigen (PSA) concentration of >2.0 ng/mL at screening, and an ECOG performance status of 0 or 1.
Patients who are likely to require chemotherapy or surgery within 2 months of initiating ADT, previously received an GnRH analog or another form of ADT for >18 months, received prior systemic treatment for prostate cancer, have brain metastases, are scheduled for major surgery after baseline, and have a history of surgical castration cannot enroll on the study.
The primary endpoint of the study is the ability of relugolix to achieve and maintain testosterone suppression to castrate levels through 48 weeks. Specifically, the endpoint was met if the lower bound of the 95% confidence interval of the response rate was ≥90%. Thus, relugolix met this endpoint, as the 95% confidence interval was 94.9% to 97.9% for the 96.7% of patients receiving relugolix who achieved sustained testosterone suppression to castrate levels.
Relugolix also showed noninferiority to leuprolide acetate on sustained testosterone suppression through 48 weeks (96.7% vs 88.8%, respectively) with a between-group difference of 7.9% (95% CI, 4.1%-11.8%), which is the primary endpoint required for regulatory submissions outside of the United States.
Moreover, pharmacodynamic data showed that there was no testosterone flare after initiation of relugolix and mean testosterone levels returned to normal levels within 90 days after treatment discontinuation.
Regarding safety, the overall incidence of adverse events (AEs) in the relugolix and leuprolide acetate arms was comparable at 92.9% versus 93.5%, respectively. A total 3.5% of patients on relugolix discontinued the trial early due to AEs versus 2.6% of those on leuprolide acetate.
The most frequently reported AEs (≥10%) in the relugolix arm included hot flashes, fatigue, constipation, diarrhea, and arthralgia. Additionally, unadjudicated major adverse cardiovascular events—which included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality—were reported in 2.9% versus 6.2% of those on relugolix and leuprolide acetate, respectively.
Prior phase II results also demonstrated efficacy with relugolix in patients with metastatic or locally advanced prostate cancer who were deemed appropriate for ADT.3 In the study, patients were randomized to 2 different doses of relugolix and leuprorelin. Results showed that relugolix had a tolerable safety profile, and that after 24 weeks, PSA levels were reduced by 97.3% to a median of 0.1 ng/mL compared with 92.4% with a median 0.2 ng/mL with leuprorelin.
“We made the decision to prioritize this NDA submission and potentially accelerate the availability of an oral treatment option for men with advanced prostate cancer,” Juan Camilo Arjona, MD, chief medical officer of Myovant Sciences, said in the press release. “This is of particular importance in the current environment and for the foreseeable future due to COVID-19 and the need for men with advanced prostate cancer to go to a clinic to receive injections in person.”
Relugolix also demonstrated superiority over leuprolide acetate in 6 of the study’s secondary endpoints, including rapid suppression of testosterone at day 4 and day 15, profound suppression of testosterone at day 15, rapid suppression of prostate-specific antigen (PSA) at day 15, and suppression of follicle-stimulating hormone at week 24 (all P values <.0001).