FDA Grants Priority Review to Relugolix for Advanced Prostate Cancer

The FDA has granted a priority review designation to a new drug application (NDA) for relugolix (Relumina) as a treatment for patients with advanced prostate cancer.¹

UPDATE 12/18/20: FDA Approves Relugolix for Advanced Prostate Cancer

The designation is based on findings from the phase 3 HERO trial, in which relugolix demonstrated superiority over leuprolide (Lupron) in sustained testosterone (T)-suppression through 48 weeks, fast T-recovery after discontinuation, and a 50% reduction in major adverse cardiovascular events (MACE) in patients with advanced prostate cancer.^2,3

Under the Prescription Drug User Fee Act, the FDA will make a decision on the NDA by December 20, 2020. The agency also stated that it is not planning to hold an Oncologic Drugs Advisory Committee meeting for this application.

If approved, relugolix would be the first and sole oral gonadotropin-releasing hormone (GnRH) receptor antagonist treatment approved for patients with advanced prostate cancer, Myovant Sciences, the developer of relugolix, stated in a press release.

“We are delighted that the FDA has accepted for priority review our new drug application for relugolix, bringing us one step closer to providing a one pill, once a day potential new treatment option to men with advanced prostate cancer,” Lynn Seely, MD, chief executive officer of Myovant Sciences, stated in the press release. “As recently published in the New England Journal of Medicine, relugolix demonstrated superior efficacy and a 54% lower risk of major adverse cardiovascular events compared to the current standard of care, leuprolide acetate injections, in the phase 3 HERO study.”

Relugolix is a GnRH antagonist given orally once daily.

In the international, pivotal, 48-week, phase 3 HERO trial, investigators randomized 934 patients with androgen-sensitive advanced prostate cancer 2:1 to receive either 120 mg of relugolix orally once daily after a one-time 360 mg loading dose (n = 624) or a 3-month depot injection of leuprolide acetate (n = 310). Testosterone recovery was also evaluated in a subset of patients (n = 184).

The primary end point was to achieve and maintain serum T-suppression to castrate levels (lower than 50 ng/dL) through 48 weeks. Key secondary outcome measures included castration rates at day 4 and day 15, profound castration (less than 20 ng/dL) rates at days 4 and 15, prostate-specific antigen (PSA) response rate at day 15, and follicle-stimulating hormone (FSH) levels at week 24.

To be eligible for enrollment, patients must have had confirmed advanced prostate cancer, had received at least 1 year of androgen deprivation therapy (ADT), a serum PSA higher than 2.0 ng/mL, and an ECOG performance status of 0 or 1. Patients were excluded from trial enrollment

if they were expecting to undergo chemotherapy or surgery within 2 months of receiving ADT, had prior ADT for more than 18 months for prior systemic cytotoxic treatment for their prostate cancer, had active liver disease, or severe cardiovascular risk conditions.

A total 563 (90.2%) patients on relugolix completed treatment compared with 276 (89.0%) of those on the leuprolide arm. Moreover, 9.5% of relugolix-treated patients and 10.3% of those on leuprolide discontinued terminated early. The remaining patients were randomized, but not treated.

Baseline characteristics were well balanced between the 2 arms. Half of patients (50.2%) enrolled had biochemical recurrence after definitive treatment for prostate cancer, 28.9% were enrolled in North America, and 11.5% were from Japan. More than 90% of patients also had at least 1 cardiovascular risk factor.

Results showed that 96.7% (95% CI, 94.9%-97.9%) of patients who received relugolix achieved and maintained castration through 48 weeks versus 88.8% of patients on leuprolide. The 7.9%-difference (95% CI, 4.1%-11.8%) demonstrated noninferiority (margin -10%) and superiority (P <.0001) of relugolix to leuprolide. Moreover, all key secondary endpoints tested also demonstrated superiority over leuprolide (P <.0001).

In the subset of patients evaluated for testosterone recovery, median T-levels were 270.76 ng/dL in the relugolix group versus 12.26 ng/dL in the leuprolide group 90 days after discontinuation of therapy.

In a prespecified analysis, MACE incidence was lower in the relugolix arm than in the leuprolide group (2.9% vs 6.2%, respectively). However, the safety and tolerability profiles of the 2 agents were generally similar beyond that factor. Adverse effects (AEs) reported for more than 10% of patients treated with relugolix or leuprolide were hot flash (54.3% vs 51.6%, respectively), fatigue (21.5% vs 18.5%), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), arthralgia (12.1% vs 9.1%), and hypertension (7.9% vs 11.7%). Notably, diarrhea occurred at grade 1/2 in severity and did not result in study discontinuation.

The investigators also indicated that treatment adherence with oral relugolix was more than 99% and similar to that seen with injectable leuprolide.

References:

1. Myovant Sciences announces priority review and fda acceptance of new drug application for once-daily, oral relugolix for advanced prostate cancer [news release]: Basel, Switzerland. Myovant Sciences. Published June 22, 2020. Accessed June 22, 2020. https://bit.ly/2BsR9mT
2. Shore ND, George DJ, Saad F, et al. HERO phase III trial: results comparing relugolix, an oral GnRH receptor antagonist versus leuprolide acetate for advanced prostate cancer. J Clin Oncol. 2020;38(suppl; abstr 5602). doi:10.1200/JCO.2020.38.15_suppl.5602
3. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. doi:10.1056/NEJMoa2004325