Repros Therapeutics Inc. is facing the daunting prospect of new pivotal studies to support a US filing of its lead candidate enclomiphene for secondary hypogonadism.

Enclomiphene is a single isomer of clomiphene citrate, a selective estrogen receptor modulator. The drug is approved for female ovulatory dysfunction, marketed under the brand name Androxal,and prescribed off-label for men with low testosterone levels.

The company announced on Dec. 1 that that its application for enclomiphene in secondary hypogonadism in overweight men with low testicular function received a complete response letter from FDA.

Repros said that according to FDA, the design of enclomiphene Phase III studies is "no longer adequate to demonstrate clinical benefit."

So for the company, it's now back to the pivotal study drawing board because FDA has asked for a new Phase III trial or trials to support approval.

"The FDA also noted concerns regarding study entry criteria, titration and bioanalytical method validation in the Phase III program," Repros said in a statement.

Repros said that it will work with the FDA to determine an appropriate path forward for the filing and that it was "disappointed that the FDA has taken this position without the benefit of an advisory committee recommendation."

FDA announced in late October that it was canceling a Nov. 3 meeting of its Division of Bone, Reproductive and Urologic Products due to questions that arose late in the review cycle that could affect interpretability of pivotal trial data ([A#14151029008]).

In an investor call at the time, the company said that although the agency cited analytical validation issues, the decision was more likely related to uncertainties about the proposed indication and appropriate population.

FDA has not established the approach for medically managing secondary hypogonadism who are not classified as “classic,” Laidlaw & Company analyst Yale Jen said in an Oct. 30 note. FDA seems to define “classic HG” as primary and secondary hypogonadism patients with only specific and well-recognized medical conditions, the analyst noted.

"All other HGs are considered as 'age related' and the FDA had not issued any guidance as how or even whether to treat them," Jen noted.

The agency should develop guidelines for managing the "dominant majority of 'non-classic' HG patients," Jen said.

During a conference call about the AdCom cancelation in late October, CEO Joseph Podolski said the company was told that the meeting was cancelled due to questions about whether the testosterone measurement methodology used by the CLIA-certified laboratory in Repros' trials was properly validated.

"One of the big discussions … that would have happened on Nov. 3 was a discussion around indication in general and who are we trying to treat," and whether the company studied the appropriate patient population, the exec said during the call.

At the time, Podolski said that the company was eager to work with FDA and scientific experts to better understand and define secondary hypogonadism, but that this process could take a year.

Repros Therapeutics Needs New Pivotal Trial For Low T Drug Enclomiphene

More from United States

More from North America