The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of relugolix (Orgovyx) for the treatment of adult patients with advanced hormone-sensitive prostate cancer, according to Myovant Sciences, the developer of relugolix.1
The CHMP based its recommendation on results from the phase 3 HERO study, which showed that 96.7% of patients randomized to relugolix maintained castration through 48 weeks, compared with 88.8% of patients receiving leuprolide (P <.001).2 The benefit with relugolix was sustained across all major secondary end points (P <.001).
Relugolix was also associated with a 54% lower risk of major adverse cardiovascular events compared with leuprolide (HR, 0.46).
Of note, relugolix did not improve castration resistance–free survival through 48 weeks versus leuprolide acetate in patients with metastatic prostate cancer.3 Overall, 74% of men who received relugolix were castration-resistance free through 48 weeks versus 75% of patients who received leuprolide (HR, 1.03; P = .84)
The European Commission will now review the opinion and make a final decision on approval. An approval would make relugolix commercially available for this indication in the European Union, as well as Iceland, Norway, and Liechtenstein.
“This positive CHMP opinion represents another step toward positioning Orgovyx as a new standard of care for men with advanced prostate cancer,” David Marek, CEO of Myovant, stated in a news release. “We look forward to providing patients and physicians in Europe with the first oral, androgen deprivation therapy treatment to further advance our mission to redefine care for men with prostate cancer.”
The open-label international phase 3 HERO trial included 930 patients treated at 155 clinical sites. The median patient age was 71 years (range, 47-97), with 28.6% of patients being aged ≥75 years. Overall, 31.7% of patients had metastatic disease, 15.5% of patients had a Gleason score of 5-6, 38.6% of patients had a Gleason score of 7, and 43.1% of patients had a Gleason score of 8-10. Half (50.2%) of patients had evidence of biochemical or clinical relapse after local primary intervention with curative intent.
The median PSA level at baseline was 10.8 ng/ml and the average testosterone level at baseline was 427.5 ± 156.2 ng/ml. The ECOG performance status was 0 in 88.1% of patients, 11.9% of patients, had prior androgen-deprivation therapy, and 30.3% had prior radiotherapy.
Patients were randomized in a 2:1 ratio to relugolix at 120 mg orally once daily or leuprolide injections every 3 months. Treatment was administered for 48 weeks, with a primary end point of sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks.
On day 4 of treatment, 56% of the relugolix cohort had castrate levels of testosterone versus 0% of the leuprolide group. On day 15, the rates were 98.7% versus 12%, respectively. Also on day 15, 79.4% of the relugolix arm had a confirmed PSA response, compared with 19.8% of patients on the leuprolide arm (P <.001).
Among a subgroup of men followed for testosterone recovery (n = 184), the mean testosterone levels 90 days following discontinuation of treatment were 288.4 ng/dL versus 58.6 ng/dL, respectively.
The incidence of adverse events (AEs) was similar across the study arms. In the relugolix group, all-grade AEs occurred in 92.9% of patients compared with 93.5% in the leuprolide arm. Grade 3/4 AEs occurred in 18% versus 20.5% of the 2 arms, respectively. There were 7 AE-related deaths in the relugolix cohort compared with 9 in the leuprolide arm.
The most common AE across all grades in both arms was hot flash, occurring in 54.3% and 51.6% of the relugolix and leuprolide cohorts, respectively. There was a higher incidence of all-grade diarrhea with relugolix at 12.2% versus 6.8% with leuprolide. All diarrhea cases were grade 1/2 and did not lead to any patient discontinuations.
Major adverse cardiovascular events occurred in 2.9% of the relugolix arm compared with 6.2% of the leuprolide cohort. The study defined major adverse cardiovascular events as nonfatal stroke or myocardial infarction, or death due to any cause.
1. Myovant Sciences Receives Positive CHMP Opinion for ORGOVYX® (relugolix) for the Treatment of Advanced Prostate Cancer. Published online February 25, 2022. Accessed February 28, 2022. https://bit.ly/3vqLTdj
2. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382(23):2187-2196. doi: 10.1056/NEJMoa2004325.
3. Myovant Sciences Announces Results of Additional Secondary Endpoint of Castration Resistance-Free Survival from Phase 3 HERO Study of Relugolix in Advanced Prostate Cancer. Myovant. Published online September 29, 2020. Accessed September 29, 2020. https://bit.ly/3iiHtLs.