A new hormonal therapy for prostate cancer is under expedited FDA review

In June, the US Food and Drug Administration (FDA) launched an accelerated review of a promising new drug for advanced prostate cancer. Called relugolix, it suppresses testosterone and other hormones that speed the cancer’s growth. If approved, this new type of hormonal therapy is expected to set a new standard of care for the disease.

Doctors give hormonal therapies when a man’s tumor is metastasizing (spreading beyond the prostate), or if his PSA levels start rising after surgery or radiation. The most commonly used hormonal therapies, called LHRH agonists, will eventually lower testosterone levels in blood. But that decline happens only after testosterone flares up to high levels as an initial response to treatment. This short-term flare-up, which lasts about a month, can cause bone pain, urinary obstruction, and other symptoms. So, doctors will ordinarily give LHRH agonists together with other drugs that prevent testosterone from interacting with cells in the body.

Alternatively, men can be treated with a different class of hormonal therapies that lower testosterone levels without the initial flare. These drugs are known as GnRH antagonists, and only one is currently available in the United States. Called degarelix, it’s given once a month by injections that can in some instances cause pain, redness, and swelling. (A different injectable GnRH antagonist, called abarelix, was withdrawn from US markets in 2005 after it caused a higher-than-expected increase in allergic reactions.)

Needle-free

Here is where relugolix enters the picture: it’s also a GnRH antagonist, but rather than being given by monthly injections, it’s taken as a daily pill.

The FDA was prompted to speed the drug’s review based on its superior performance during a late-stage clinical trial. The study investigators enrolled 934 men from 155 hospitals in the United States and Japan. Half the men had elevated PSA levels after having been treated already for prostate cancer. The rest had newly diagnosed metastatic cancer, or more localized prostate tumors that weren’t suitable for surgery. A total of 622 were treated with relugolix, and 305 men were given an LHRH agonist called leuprolide. All the men were treated for 48 weeks.

By all measures, relugolix came out ahead. The drug lowered testosterone to acceptable therapeutic levels within four days, whereas in the leuprolide-treated men, testosterone initially surged to an average of more than ten times the target concentration before dropping below it 29 days later. Furthermore, normal testosterone levels were restored within 90 days after relugolix treatment was discontinued. By contrast, just 3% of the leuprolide-treated men achieved normal testosterone levels within that same duration after treatment. That testosterone levels go back to normal after hormonal therapy is important for quality of life, including among men who receive the treatment intermittently.

Dr. Marc Garnick, Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, points out that relugolix also had a better safety profile for measures of heart health. It’s long been known that hormonal therapy in general can have cardiac toxicities, especially among men with pre-existing risk factors such as diabetes, hypertension, or a prior heart attack. But during this clinical trial, fewer men in the relugolix group experienced significant cardiac side effects after 48 weeks of treatment.

“This is an important study, as it demonstrates the ability of a GnRH antagonist to be administered as an oral drug,” Garnick said. “The continued development of GnRH antagonists has many advantages compared to drugs that require an obligatory increase in testosterone before achieving their desired effects. The oral availability of relugolix may also lessen some of the local skin reactions that are common with degarelix, or some of the allergic reactions that occurred with abarelix.”

The FDA is expected to make a decision on the drug’s approval by December 20, 2020.

Disclosure: Dr. Garnick has been named as a scientific advisor to Myovant Sciences (the developer of relugolix) and is a shareholder in the company. He was also a developer of abarelix and previously served as an advisor to Ferring Pharmaceuticals, the developer of degarelix.

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