VERU-944 is for the treatment of hot flashes caused by prostate cancer hormonal therapies in men with advanced prostate cancer.

VERU-944

Scientific Overview

Prostate cancer is the most common non-cutaneous cancer diagnosed in men with over 160,000 new cases expected in 2017 (American Cancer Society. Cancer Facts & Figures 2017). The estimated prevalence of prostate cancer is 2.35 million cases for which over one-third will have received androgen deprivation therapy. Hot flashes, also known as vasomotor symptoms, are the most common and distressing side effect of hormonal therapies for the treatment of advanced prostate cancer. Hormone therapies include androgen deprivation, like LUPRON (leuprolide) or ZOLADEX (goserelin), as well as the newer agents approved to treat advanced prostate cancer such as ZYTIGA (abiraterone) and XTANDI (enzalutamide). Up to 80% of men on androgen deprivation therapy complain of hot flashes (Frisk J, Maturitas 65:25-22, 2010). Hot flashes are defined as intense heat sensation, flushing and profuse sweating and chills as well as anxiety and palpitations. Although episodes of hot flashes occur repeatedly and last a few minutes, some may last up to 20 minutes. Hot flashes associated with prostate cancer hormonal therapies tend to persist over time with consistent frequency and intensity throughout therapy. Up to 50% of men continue to report hot flashes after five years on prostate cancer hormonal therapy (Frisk J, Maturitas 65:25-22, 2010). Patients on prostate cancer hormonal therapy report significant effects on daily functioning and quality of life. Hot flashes are the main reason for patients to be noncompliant with their prostate cancer hormonal therapy. As prostate cancer patients with advanced and metastatic disease are living longer as a result of more effective hormonal therapies, hot flashes have become an even bigger concern and impact on quality of life.

Hormonal and non-hormonal therapies have been used off-label to treat hot flashes in men on prostate cancer hormonal therapies. In general, hormonal agents especially estrogens are effective. However, estrogen treatment is complicated by lack of consistent dosing, dose dependent gynecomastia (breast enlargement), gynecodynia (painful breasts) and increase in thromboembolic events. Non-hormonal agents that have been used off-label include anti-seizure agents and antidepressants that have bothersome side effects. Moreover, non-hormonal agents tend to be less efficacious than hormonal therapies for the treatment of hot flashes. There are no FDA-approved therapies for hot flashes caused by prostate cancer hormonal therapy in men with advanced prostate cancer. VERU-944 is cis-clomiphene (zuclomiphene), a potent nonsteroidal estrogen receptor agonist. Clomiphene, which contains 30-50% zuclomiphene, appears to be well-tolerated in 39 published studies in over 2,200 men with doses as high as 400 mg/day and up to three years of use. A nonsteroidal hormone therapy like VERU-944 has the potential to be an effective and well-tolerated treatment for hot flashes resulting from the use of hormonal therapies in men with advanced prostate cancer.

VERU-944

Development Plan

As VERU-944, zuclomiphene, comprises 30-50% of CLOMID (clomiphene citrate) which is approved for the treatment of ovulatory dysfunction in women desiring pregnancy, Veru will be able to reference the nonclinical and clinical safety information from both the listed drug labeling and the published literature under the 505(b)(2) regulatory pathway. Veru held a pre-IND meeting with the FDA, and anticipates filing the IND in 2017 and plans to initiate a Phase 2 clinical study in early 2018.

VERU-944

Market

Hot flashes are the most common side effect of prostate cancer hormone therapy occurring in up to 80% of men, with about 30% having moderate to severe hot flashes. Approximately 700,000 men annually in the United States are on androgen deprivation therapy, abiraterone or enzalutamide for advanced prostate cancer. There are currently no FDA-approved therapies for hot flashes associated with prostate cancer hormonal therapies. The annual U.S. market for the treatment of hot flashes in men on prostate cancer hormonal therapies is estimated to be $600 million per IMS.