QuatRx's Ophena positive in Phase III trial of postmenopausal vaginal atrophy
This article was originally published in Scrip
QuatRx's lead drug candidate, Ophena (ospemifiene), improved symptoms of postmenopausal vaginal atrophy in a second Phase III trial, show top-line data. The private, Michigan-based, company plans to file the drug with the US FDA early next year.
The results are also in line with a previously reported positive Phase III trial in 826 women with vulvovaginal atrophy. These two trials are sufficient for a filing, said a company spokesman.
For the second of two pivotal trials of the oral selective oestrogen receptor modulator (SERM), the company enrolled 919 women with vulvovaginal atrophy. Subjects were divided into two cohorts on the basis of their most bothersome symptom – those who suffered most from vaginal dryness or those who suffered most from dyspareunia (pain during intercourse). All patients were treated daily with 60mg of Ophena or with placebo for 12 weeks, and were given a non-hormonal vaginal lubricant for use as necessary. As per the US FDA's stipulations, the trial had four co-primary endpoints: decrease in percentage of parabasal cells in a vaginal smear; increase in percentage of superficial cells in a vaginal smear; decrease in vaginal pH; and improvement in a patient’s most bothersome symptom (either dyspareunia or vaginal dryness, as per the two cohorts).
In the cohort of 605-women suffering from dyspareunia, the drug met all four primary endpoints (p?0.0001), the company has now reported. Full results will be released at a later date.
In the cohort of 314 women suffering predominantly from vaginal dryness, the drug met all of its co-primary endpoints in the per protocol population, but not in the intent-to-treat population, the company reported earlier this year.
The cohorts cannot be combined, but rather the efficacy of the drug in the most bothersome symptom cohorts must be calculated separately, a company spokesman told Scrip. "Effectively, it was two studies," the spokesman said. However, the cohorts were combined under the auspices of a single trial for simplicity, with the same protocol and carried out at the same sites.
Vulvovaginal atrophy is currently treated with oestrogen-based therapies, which have been linked with increased cancer risk. And some SERMS, such as the breast cancer drug tamoxifen, have previously been linked to endometrial cancer and other serious adverse events. But Ophena does not carry this risk, said the company spokesman. In a long-term Phase III safety trial, 360 women were treated with Ophena, while 60 were treated with placebo, for one year. The trial showed that the drug was well tolerated, and no cases of endometrial hyperplasia, carcinoma or breast cancer were identified.
Ophena is the only SERM in late-stage development for vulvovaginal atrophy, and no other SERMs have been approved for the indication, says the company.
The company's fispemifene, a selective oestrogen receptor antagonist for secondary hypogonadism in men, is in Phase II trials, and its sobetirome, a selective thyroid receptor beta agonist, is in Phase I trials for dyslipidemia.