Repros Therapeutics Inc.'s CEO Joseph Podolski acknowledged the "nauseating" Wall Street ride for the company of late, but told investors during a conference call that "with time and continued progress, our share prices are going to move in the right direction."

The stock started along that route Friday, when Repros (NASDAQ:RPRX) surged 57 percent to close at $10.12, up $3.67, on word of an encouraging meeting with the FDA on the new drug application (NDA) for Androxal (enclomiphene), an oral estrogen receptor antagonist for secondary hypogonadism.

U.S. regulators did not say more studies would be necessary to file the NDA, although the agency noted that cardiovascular safety trials may be called for later. "Cardiovascular risk is always a concern for any new chemical entity," Podolski said, but he "didn't get the sense from the meeting that there's some special need here. We're going to do our best to keep the time line," filing the NDA by the end of the year.

In October, The Woodlands, Texas-based firm said it needed to provide more information about the compound, as the FDA changed its next meeting with Repros from a type B to a less-routine type C session. Repros lost 40 percent on Wall Street that day. Two months earlier, the stock had risen 18 percent on positive results from one of a pair of phase III trials with Androxal. (See BioWorld Today, Aug. 29, 2014, and Oct. 20, 2014.)

The back-and-forth with the FDA may be settling down, and Podolski said the firm will "begin to talk a bit more about the European opportunity" soon.

Piper Jaffray analyst Joshua Schimmer was wary but optimistic. "While there may be a slight delay to the filing to prepare an environmental safety analysis, overall this sounds like a positive step forward to having the Androxal profile evaluated for approval," he said, noting that "ultimately, the FDA will have to weigh the safety/efficacy profile of the drug to determine if the application is approvable, and we remain neutral on shares until we have greater visibility on that front."

The FDA asked for an environmental assessment, given the potential implications of Androxal or metabolites entering the environment. Repros does not need to have the assessment finished in order to file the NDA, but must have an evaluation framework established.

"It's related to people taking the drug, passing the drug through their body into the waste-treatment system," Podolski explained in response to questions. The company determines how many metric tons of the drug will be used in the U.S., and then calculates what will be the potential concentration in the waste treatment system. The working theory is that "the solution to pollution is dilution," and as long as the concentration is below 1 part per billion, the agency is satisfied, Podolski said – and Androxal is "well within the range."

'STARTING TO COME TOGETHER'

The FDA's rep "kind of did a little song and dance" when Podolski pointed out that Androxal in this way is similar to at least one recently approved compound, he recalled, adding that U.S. regulators seem to be edging toward requirements like those overseas. "In Europe, there's no such thing as a categorical exclusion," he said "If you work at a given drug long enough, you're bound to catch every new thing that the FDA comes up with."

FDA officials provided "no indication that [it] will have issues with the use of testosterone as a surrogate for clinical benefit in these patients," Schimmer conceded. "That said, we struggle to understand how the recent testosterone-gel panel results can be reconciled with an approval of Androxal without symptom benefit data, but as we have said before, stranger things have happened," he wrote in a research report.

Podolski mentioned the panel in his remarks, saying that too many people were "fixated" on the outcome there. But the committee was "about hormone replacement," he said. "We're not hormone replacement."

Schimmer was referring to the September two-day meeting of the FDA advisors to decide about their view of proposed changes in labels for testosterone replacement therapy (TRT) products. The first day ended with a 20-1 vote that the drugs ought only to be used in classic hypogonadism – low testosterone due to testicular or disease of the hypothalamic/pituitary glands. Regulators asked the panel to determine whether TRTs should be prescribed for men whose condition is related to age, given the scarcity of efficacy and safety data related to using the drugs as a way to boost energy and cure the flagging sex drive in elderly males. Voters advised such a label not be allowed without complete safety and efficacy data. Repros shares took a hit that day, too, dropping 25 percent. (See BioWorld Today, Sept. 19, 2014.)

The latest news, though, signals the possibility that gatekeepers are starting to understand Androxal as the drug that it is, rather than as a TRT. "I'd have to say this was probably the most constructive meeting I've ever attended," Podolski said. "Over the course of the meeting they gave us very clear guidance as to how they would like to have our data presented, including a "pretty lengthy discussion about efficacy that I think was very favorable for us."

In Podolski's view, "the screw is beginning to turn," with regulators and everyone else starting to understand how Androxal restores the body's ability to produce its own testosterone. "We've still got a way to go, but I think it's starting to come together. I think where we're going with this is a good place," he said. Men targeted by the compound have metabolic disorders, Podolski said. "It's not aging. It's not about libido."