It looks as if Allergan’s (NYSE:AGN) uterine fibroid drug Esmya is finally going to break America. Four years after it reached market in Europe, the selective progesterone receptor modulator has hit big in the first of its pivotal US trials, and Allergan’s shares rose 6% yesterday as investors consider its potential sales – currently forecast at over $500m.
Approval is not quite certain yet. A second phase III trial will have to read out before Allergan can file with the FDA, and that is not due until early next year. Still, the win in the Venus I trial was emphatic, and if Venus II is similarly impressive, some analysts believe that global sales could climb closer to $1bn.
The Venus I study forms part of the second attempt to get Esmya to the US as a therapy for fibroids. The first was shelved in 2012 (Allergan's uterine fibroid pill and BioMarin's Kuvan follow-on, February 12, 2016).
Venus I enrolled 157 premenopausal women, 101 of whom were randomly assigned a single 5mg or 10mg Esmya (ulipristal acetate) pill each day for 12 weeks, and 56 of whom received placebo. The drug did not disappoint: 58% of the patients given 10mg of the drug and 47% given 5mg had no abnormal bleeding, one of the co-primary endpoints, compared with 1.8% on placebo.
The other co-primary endpoint, time to absence of bleeding, was also met with significance by both treatment arms, Allergan said, though the company did not give details.
As for the secondary efficacy endpoints, 58% of patients given the 10mg dose and 43% of those given the 5mg dose achieved absence of bleeding from day 11 to the end of treatment; none of the placebo-treated patients achieved this. Improvement from baseline on a scale designed to measure fibroid patients’ quality of life was 59 points in the 10mg group, 52 points in the 5mg group and 21 points with placebo; both doses were significantly superior to placebo.
Esmya’s showing on safety was also good, with no serious side-effects and no patients ceasing treatment due to adverse events. This is important as many hormonal therapies for fibroids, including AbbVie’s market-leading Lupron, cause menopause-like side-effects such as hot flushes that mean they can only be used short-term.
Allergan said that Esmya could become the first non-invasive long-term treatment for uterine fibroids in the US. But analysts at Evercore ISI insisted that it is not a chronic therapy. In Europe, the drug is dosed in a 12-week course, and the analysts say it is possible that the FDA could limit the maximum number of cycles to two.
On the approval indications, though, the FDA might be more liberal than other regulatory authorities. In Europe and Canada Esmya may only be used as a pre-operative treatment for patients due to undergo fibroid removal or hysterectomy. In the US, the FDA is allowing Allergan to enroll patients with signs and symptoms of fibroids who are not necessarily preparing for surgery.
If it is approved for use in this population, its market will expand sharply. At most, 300,000 hysterectomies owing to fibroids are performed in the US, but the total number of women with uterine fibroids in the US is closer to 15 million. Around five million will seek treatment each year, according to Evercore ISI.
In order to have a hope of accessing these patients, Venus II will have to hit as convincingly as Venus I when it reports at the beginning of 2017.
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