Repros’ Androxal Primed For NDA Submission, But Outcomes Study Looms
This article was originally published in The Pink Sheet Daily
Executive Summary
The testosterone drugmaker is confident that Androxal can gain approval and is on track to submit a filing with FDA this year, but talk of a cardiovascular outcomes study is still on the table.
Repros Therapeutics Inc. says Androxal is on track to be filed with FDA by year-end and that a cardiovascular outcomes study is not likely needed for approval. Yet, the large costly trial will likely be a post-marketing reality for the testosterone drug despite the company’s claims that it doesn’t have the same issues as testosterone replacement therapies.
The Woodlands, Texas-based biotech hosted a conference call Nov. 7 to convey to investors the specifics of its recent pre-NDA meeting with FDA earlier in the week, with CEO Joseph Podolski calling the meeting the “most constructive meeting I’ve ever attended.” The company announced late last year that it would have to delay the filing until the fourth quarter of 2014 due to issues that cropped up at one site used in its clinical testing – the site was excluded from one study to avoid any problems with the data (Also see "Repros Low-Testosterone Therapy NDA May Be Delayed Until 4Q 2014" - Pink Sheet, 23 Oct, 2013.).
He admits that the company went into the meeting with the regulatory agency with a “long list” of questions and that certain subjects stuck out – in particular, “a very favorable discussion about efficacy,” an environmental impact study and a CV outcomes study.
“CV outcomes came up, but I didn’t get the sense that it was a particular need here,” said Podolski. “It may come up [post-market], but I don’t think it will be needed for approval.”
The firm’s press release on the meeting noted that, “Although no specific request was made, the FDA stated that as a result of the recent Advisory Committee Meeting [on testosterone products], cardiovascular risk is of particular interest and that additional safety studies could be required in the future.”
Cardiovascular risk has become a hot button issue for testosterone replacement therapies, mostly topical creams and gels that have gained popularity to treat age-related hypogonadism – commonly referred to as “Low-T” (Also see "Testosterone Replacement Safety Gets FDA Panel Review As Lawsuits Pile Up" - Pink Sheet, 14 Jul, 2014.). The drugs are used by more than 2.3 million U.S. men, according to FDA, and bring in billions of dollars for pharmaceutical companies, but safety concerns have prompted the agency to take a closer look at the products and have started to curb sales of the drugs, which are only approved for conditions associated with a deficiency or absence of endogenous testosterone. Low-T is considered an off-label use (Also see "‘Low-T’ Drugs Need Randomized CV Safety Trials, FDA Panel Says" - Pink Sheet, 18 Sep, 2014.).
Repros argues that Androxal (enclomiphene citrate) should not be put in the same category as other testosterone replacement drugs. “We’re not replacing hormones, we are normalizing a man’s own ability to produce testosterone,” the exec said during the call (Also see "Androxal Vs. Testosterone Gel Head-To-Head Trials Get FDA Pumped" - Pink Sheet, 10 Feb, 2014.).
Androxal is a single isomer of the selective estrogen receptor modulator clomiphene citrate, which is FDA-approved for female ovulatory dysfunction and prescribed off label by specialists for men with low T. Repros is developing the drug specifically for secondary hypogonadism, which is associated with obesity. Primary gonadism refers to low testosterone caused by problems with testicles, whereas secondary disease is caused by problems with the pituitary gland or hypothalamus in signaling to the testicles to make testosterone. The company believes that treating the cause of low testosterone – through restoration of pituitary function – minimizes the drawbacks of giving testosterone topically, including loss of fertility and potential risk for cardiovascular events.
Other NDA Requirements
The biotech also mentioned that FDA would like it to complete an environmental impact study to include in its NDA filing. Podloski said this is on track and doesn’t expect it to delay filing.
The study measures the amount of drug that makes it into the water supply through excreted waste. Environmental impact assessments are conducted to see if there could be serious harm caused by expected exposure levels or if there could be adverse effects on certain species. These sorts of studies are often conducted with veterinary medicines that may make it into the food supply. Testosterone treatments have been known to have ill effects on women and children when the topical medications rub off onto other people, causing abnormal hair growth and other masculine changes.
The company added that FDA would like to hold a conference call with the contractor conducting the study before submission of the NDA. The company did not disclose who has been contracted to conduct the study.