Interim Phase 2 trial results show that Veru‘s experimental treatment zuclomiphene citrate is well-tolerated and significantly reduces hot flashes in advanced prostate cancer patients using androgen deprivation therapy (ADT).
These topline findings are from the first 93 men enrolled in the trial (NCT03646162), all of whom were having moderate-to-severe hot flashes caused by ADT treatment.
Men given a 50 mg oral dose of zuclomiphene experienced a 41% reduction in those hot flashes at six weeks post-treatment compared to pre-treatment (baseline), a “statistical and clinically meaningful reduction … without any clinically relevant safety findings,” the company reported in a press release.
Veru is now planning to open a pivotal Phase 3 trial of zuclomiphene by mid-year. Data from this trial is expected to support a request for zuclomiphene’s approval to treat ADT-induced moderate-to-severe hot flashes in men with prostate cancer.
“This is an exciting time for Veru. These Phase 2 clinical interim results have established that zuclomiphene has clinically meaningful estrogen activity against moderate to severe hot flashes with a good safety profile, allowing us to advance to a pivotal Phase 3 clinical trial of zuclomiphene,” said Mitchell Steiner, MD, chairman, president and CEO of Veru.
ADT is a common hormone treatment for prostate cancer patients, and works by lowering the level of testosterone in the body. But testosterone is needed to produce estrogen in men, which in turn regulates body temperature. Patients undergoing ADT commonly report hot flashes as a severe side effect of the treatment.
Hot flashes have as a main symptom a subjective sensation of a rise in temperature in the face and trunk, accompanied by a dilation of blood vessels in the skin, which is often followed by sweating.
These flashes can range in frequency and intensity, lasting from a few seconds to 20 minutes in severe cases, and often persist throughout the course of androgen deprivation therapy. They can also cause anxiety, palpitations, interrupted sleep, and cognitive difficulties.
Zuclomiphene citrate is an oral nonsteroidal estrogen receptor agonist that increases the levels of estrogen. It has never been approved for any indication, but evidence from 39 studies involving 2,200 men suggest it is well-tolerated for up to three years of use.
The ongoing Phase 2 trial is currently recruiting up to 120 eligible adults at many of its 24 clinical centers in the United States. It is designed to assess multiple doses of zuclomiphene citrate — ranging from an expected no-effect dose of 10 mg to 100 mg — or a placebo. Its main goal is to determine changes in the frequency of moderate to severe hot flashes from the study’s start to week six.
Researchers note that moderate hot flashes are defined as a sensation of heat with sweating that allow men to continue their activity, while severe hot flashes cause men to cease activity until the intensity of the flash eases.
Secondary goals include changes in the severity of hot flashes in the same six-week period, changes in severity and frequency across several points in time, and improvements in bone markers. Additional assessments include measures of tumor progression, testosterone levels, and safety.
The 93 patients included in this interim analysis had received daily oral doses of either 10 mg or 50 mg zuclomiphene. As expected, men given the lowest dose showed a non-significant reduction in hot flashes from baseline to week six, while those on the higher dose experienced a significant 41% reduction during that same period.
The 50 mg dose was also significantly better than the 10 mg dose at increasing estrogen levels.
No serious adverse events or treatment-related adverse events have been reported so far. Adverse events commonly seen with other hot flash treatments — like breast enlargement, pain, blood clots, or stroke — were also not reported in this trial.
“Without the side effects seen with steroidal estrogens or progestins, we believe that zuclomiphene has the potential to be the first FDA approved therapy for ADT-induced hot flashes to address this area of significant unmet medical need,” Steiner said.