Repros Therapeutics Inc.'s first pivotal study, called ZA-301, with the hypogonadism therapy Androxal (enclomiphene) hit both of its primary endpoints – testosterone and sperm count – in the intent-to-treat population, as mandated by the FDA, and CEO Joseph Podolski said the $2 billion demand for such therapies could get bigger than the market for erectile dysfunction drugs.

"When you lay our drug next to what's currently approved, there is no comparison," Podolski said during a conference call with investors. Whatever the market turns out to be, "we should easily dominate as much as 50 to 75 percent of it," he added.

Repros' stock (NASDAQ:RPRX) closed Thursday at $15.51, up $6.38, almost 70 percent. A second pivotal trial, ZA-302, likely will be fully enrolled in May. "I think the prognosis for 302 looks good," Podolski said.

ZA-301 randomized 151 subjects, 38 given placebo and 113 getting Androxal, an estrogen receptor antagonist. The primary testosterone endpoint required that 75 percent of the subjects in the drug arm exhibit a 24-hour average total testosterone in the normal range (300–1040 ng/dL) at the end of 12 weeks of treatment.

Androxal surpassed the goal. Seventy-nine percent of Androxal men turned up 24-hour average testosterone levels in the normal range, and none went above – an important safety factor. In sperm count, men in the study showed the necessary noninferior criteria of 20 percent, comparing the drug to placebo.

"I'm not a big fan of this [sperm-count] endpoint, but it is what it is," Podolski said, noting that, since Androxal increases follicle-stimulating hormone, sperm production should go up. "At the same time, if you're increasing testosterone – I know we've gone around and around on this dance before – [which] drives libido, it's going to drive sexual frequency," which will act to lower the sperm count.

Androxal pulled through, despite glitches that included a fabricator of "data" at a site in California who was fired, and some weirdly unbalanced real data from a site in Miami.

In California, a woman wrote down sperm counts of men whose levels had not actually been measured, so those numbers could not be used.

"That's clear fraud," Podolski said. "Obviously, that site has fired their coordinator, and thank goodness we had a diligent coordinator on our side [who] dug in and found" the dishonest reporting.

Half of the men in the drug treatment arm of the trial whose sperm dropped below 50 percent were enrolled at a site in Miami, yet not a single subject from the site who took placebo showed such a degree of lowering.

"That was certainly strange, so we [sent] our new group leader down to query the investigator," Podolski said. "It turns out this is a site that caters predominantly to Cubans." And Cubans, the group leader learned, culturally tend to have a lot of sex.

"It also turns out that they cater to gay Cubans," Podolski went on. "So . . . interesting concept. I guess if I were ever to run a study looking at the impact of our drug or a testosterone product on libido that might be a group that we'd want to study."

Podolski said the second pivotal trial with Androxal includes plenty of sites in the north and other parts of the country, for a more diverse patient population, in terms of sexual activity. "We've got a bunch of old married men, and libido's been beaten out of us over the years," he joked.

'Wolves Crying in the Forest'

In the testosterone market, Repros would go up against the likes of Auxilium Pharmaceuticals Inc., of Malvern, Pa., with its Testim patch, already beset by "weak trends" this year, noted Leerink Swann analyst Joseph Schwartz in a research report.

Oral Androxal represents "a new mechanism drug that appears to treat the disorder in a more physiologic manner than the gel testosterone replacement therapies that may actually be counterproductive, so depending on who ends up with this asset it could be disruptive to the current standard-of-care therapies like Testim," Schwartz wrote. The market could heat up as early as 2015. Schwartz already expects Testim revenues to dip in 2016, thanks to an authorized, generic AndroGel [testosterone gel, Solvay Pharmaceuticals Inc.] due from Activis Inc. (formerly Watson Pharmaceuticals Inc.), per a settlement with the originator of the branded form. More are coming down the pike.

Androxal, because it's not a straight hormone replacement product like the others, has an advantage in a market already larger than some believe, and certain to grow even more before Repros' own intellectual property protection expires in the mid-2020's, Podolski said.

"I think the main driver here is the direct-to-consumer advertising that big pharma is putting into it," he said. "Clearly, when Auxilium or Solvay was out there on their own, it looked interesting, but certainly didn't look like the opportunity we see today."

Age and weight gain – one inevitable, the other an epidemic – are the two main causes for low testosterone in men, "and it happens much earlier than we might appreciate," Podolski said. "Certainly, the urology community is beginning to take note that there might be a more rational approach." Thirty million men in the U.S. are at risk of lowered testosterone, on "the slippery slope of becoming obese," he added.

"We've been the wolves crying in the forest for the longest time," Podolski said, calling the latest trial results "a very important first step." So far, Androxal is unpartnered, but the size of the still-growing demand for testosterone therapy points to the importance of finding one. "We would be foolhardy to take this on by ourselves," he said.