Relugolix Induces Sustained Testosterone Reduction in Advanced PC, HERO Phase 3 Trial Results Show

Treatment with Myovant Sciences’ relugolix induces a long-lasting reduction in testosterone to castrate levels — similar to testosterone levels after medical or chemical castration — in nearly all men with advanced prostate cancer who are sensitive to androgen deprivation therapy, updated results from the HERO Phase 3 trial show.

In addition to meeting its primary goal — sustained castration from weeks 5 to 48 of treatment — the trial met six additional secondary goals. These included a faster testosterone suppression than standard treatment with leuprolide acetate, and a rapid drop in prostate specific antigen levels, which are a marker of prostate cancer.

The results will support the submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the second quarter of 2020, as well as submissions to Japan’s and Europe’s regulatory agencies.

“With the exciting results from the HERO study demonstrating the potential of relugolix to provide unique benefits compared to leuprolide, we look forward to submitting an NDA to the FDA,” Lynn Seely, MD, president and CEO of Myovant Sciences, said in a press release. “We are now closer to our goal of bringing a precision oral medicine to the broad spectrum of men with advanced prostate cancer.”

Testosterone, the primary male sex hormone, is a major driver of prostate cancer. A common approach for treating such cancer is reducing the amount of testosterone produced in the body. This approach is called hormone therapy, or androgen-deprivation therapy, and aims to reduce testosterone below castrate levels.

Hormone therapy is often delivered in the form of luteinizing hormone-releasing hormone (LH-RH) agonists, such as leuprolide acetate, which is marketed under the brand names Eligard and Lupron.

These treatments work to reduce the amount of sex hormones in circulation — estrogen in women and testosterone in men — but have some limitations. One such limitation in men is an initial rise in the sex hormone levels, known as testosterone flare, which can exacerbate symptoms and delay testosterone recovery after the end of the treatment.

Relugolix is a different form of hormone therapy that reduces testosterone by inhibiting the gonadotropin-releasing hormone (GnRH) receptor. Essentially, it’s a different mechanism for reducing sex hormones.

The randomized, international HERO trial (NCT03085095) was designed to determine if relugolix is better than standard leuprolide acetate at lowering testosterone levels to castrate levels, which is less than 50 nanograms per microliter.

It was expected to enroll 1,100 men with advanced prostate cancer who had been receiving continuous androgen-deprivation therapy for at least one year. The study is being conducted at more than 180 clinical centers across North and South America, Europe, and the Asia-Pacific region.

The trial met its primary goal, with 96.7% of participants achieving sustained castration levels from week 5 through week 48. This was non-inferior to the response obtained in the leuprolide acetate group (88.8%).

In addition, the trial met several secondary endpoints by showing that relugolix suppressed testosterone, prostate-specific antigen (PSA), and follicle-stimulation hormone (FSH) faster and more effectively than leuprolide.

The therapy was not associated with testosterone flares, and hormone levels returned to normal within three months after the end of treatment, the results showed.

The occurrence of adverse events was similar for relugolix and leuprolide — 92.9% vs. 93.5% — and a similar proportion of participants discontinued treatment due to adverse events (3.5% vs. 2.6%). The most frequent adverse events in the relugolix group were hot flashes, fatigue, constipation, diarrhea, and joint pain.

“An oral gonadotropin-releasing hormone, or GnRH, antagonist for advanced prostate cancer has been an aspiration for many years,” said Neal Shore, MD, medical director of the Carolina Urologic Research Center and HERO program steering committee member. “If approved, relugolix would become the first-of-its-kind oral option for men with advanced prostate cancer.”