Relugolix, a form of hormone therapy for prostate cancer, has failed to significantly extend the time men with advanced disease live without acquiring resistance to castration medications, compared with standard-of-care leuprolide acetate, updated findings from the HERO trial show.
While the trial (NCT03085095) had met its primary goal of increasing the proportion of patients achieving sustained testosterone reduction through 48 weeks, along with several other secondary endpoints, it now failed to demonstrate the benefits of relugolix in this additional secondary measure.
“These new data from the Phase 3 HERO study show that three out of four men with metastatic prostate cancer remained castration resistance-free through 48 weeks while on oral relugolix, in-line with leuprolide acetate injections, the current standard of care,” Dan George, MD, a professor at the Duke University School of Medicine, said in a press release.
“I continue to be excited by relugolix as a potential new and differentiated treatment option for men with prostate cancer given its robust clinical and safety data, including the lower risk of major adverse cardiovascular events compared to leuprolide acetate,” added George, a HERO program steering committee member.
Relugolix, developed by Myovant Sciences, is an oral small molecule that inhibits gonadotropin-releasing hormone (GnRH) receptor, a protein in the brain. In males, blocking the activity of this protein stops the release of hormones that stimulate testosterone production, ultimately lowering testosterone levels in the body.
The testosterone hormone has been found to drive the growth of some prostate cancers. As such, androgen deprivation therapy (ADT), which involves lowering testosterone levels in the body, is a mainstay of treatment for such cancers.
The U.S. Food and Drug Administration (FDA) granted relugolix priority review in June as a potential prostate cancer treatment, with a decision on its new drug application expected before the end of the year. If it gets approved, relugolix would become the first and only oral GnRH receptor inhibitor to be approved for the treatment of advanced prostate cancer in the U.S.
“With our New Drug Application under Priority Review by the FDA, we look forward to our target action date in December 2020 and hope to advance our commitment to redefining care by bringing once-daily, oral relugolix to men with prostate cancer,” said Lynn Seely, MD, the CEO of Myovant Sciences.
Myovant’s application for the investigational medicine is supported by data from the ongoing HERO Phase 3 trial, which is comparing relugolix to leuprolide acetate in approximately 1,100 men with advanced prostate cancer. HERO is still recruiting participants in China; additional information on study locations is available here.
Leuprolide acetate — marketed under the brand names Eligard and Lupron — is a conventional ADT that is currently the standard of care treatment. Like relugolix, it is designed to lower testosterone levels in the body, though the exact biological mechanisms by which this is accomplished are different. Of note, whereas relugolix is taken orally, leuprolide acetate is given via injection.
The trial’s main goal was to assess whether relugolix could lower testosterone levels as effectively as the comparator, here the standard-of-care therapy. Previously reported results showed that, after 48 weeks of receiving the medicine, 96.7% of participants treated with relugolix had castration levels of testosterone. In effect, their testosterone levels were low enough to suggest no testicular production of the hormone. Of those treated with leuprolide acetate, 88.8% achieved castration levels.
The two medications were found to have similar rates of adverse events. But previous data demonstrated that the rate of serious adverse events affecting the heart was more than halved among participants treated with relugolix, relative to those given leuprolide acetate (2.9% vs. 6.2%).
The new data now reported by Myovant concerned a secondary endpoint of the HERO trial: castration resistance-free survival, or the time patients lived without becoming resistant to castration.
While some prostate cancers will initially respond to ADT, most will start to grow even in the absence of testosterone signaling. Such cancers are said to be castration-resistant; as such, the castration resistance-free survival rate refers to the proportion of people who are alive and whose tumors are still responding to the ADT.
In the trial, 74% of patients treated with relugolix remained alive and responding to ADT throughout the 48 weeks of treatment, compared with 75% of those on leuprolide acetate.
“We believe the totality of data — including previously reported data from the Phase 3 HERO program, published in The New England Journal of Medicine — presents compelling evidence for the potential use of relugolix in men with advanced prostate cancer,” Seely said.
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