Forecasts for Allergan’s uterine fibroid therapy Esmya had already plunged after a liver safety scare earlier this year, and an FDA knockback yesterday confirmed the project’s dismal prospects.
Esmya now looks like an also-ran in the uterine fibroid market, which is set to be dominated by Abbvie’s elagolix. More importantly, the news makes it unlikely that Allergan will be able to offload its women’s health business. This was one of the units it put on the auction block in May, and Esmya is its second-biggest product.
Esmya is marketed in Europe for fibroids, by Gedeon Richter, but reports of liver injury late last year prompted a review by the EMA, which has now restricted its use.
These safety concerns were behind the FDA’s reluctance to give the project the green light in the US, despite wins in the pivotal Venus I and II trials.
Allergan said it would meet the FDA to discuss its next steps, but even if Esmya does eventually get the go-ahead it could have a tough job competing against elagolix. Abbvie’s product is only approved in endometriosis-associated pain, as Orilissa, but phase III success in fibroids earlier this year put a filing in the new indication on track for 2019.
Until the FDA knock-back Esmya was expected to be Allergan’s second-biggest women’s health product in 2024, behind the contraceptive pill Lo Loestrin. Stifel analysts scathingly described the rest of the group’s women’s health franchise as “a mostly genericised portfolio [with] no tangible pipeline”.
|Allergan's top 10 marketed women's health products|
|Annual sales ($m)|
|Product||Indication||Mechanism of action||2017||2024e|
|Lo Loestrin FE||Female contraception||Oestrogen & progesterone receptor agonist||459||644|
|Cervidil||Cervical ripening during labour||PGE2 regulator||58||58|
|Crinone||Female infertility, amenorrhoea||Progesterone receptor agonist||41||35|
|Trelstar||Endometriosis-associated pain||Luteinizing hormone/choriogonadotropin receptor agonist||29||23|
|Minastrin 24 FE||Female contraception||Oestrogen & progesterone receptor agonist||61||8|
|Allergan's women's health pipeline|
|Contraceptive Vaginal Ring||Female contraception||Oestrogen & progesterone receptor agonist||-||-|
|Estradiol Capsule||Atrophic vaginitis||Oestrogen receptor agonist||-||25|
|BotuGel||Overactive bladder, urinary incontinence||nAChR antagonist; SNAP25 inhibitor||-||-|
|Proellex-V||Uterine fibroids||Progesterone receptor antagonist||-||-|
It is hard to see who would buy this for $4-5bn – the price tag that was touted when Allergan said it was looking to offload the business, along with its infectious disease portfolio, in May.
The company has not yet sold either unit, but did agree to divest its dermatology products to Almirall in August for $550m.
Few options... for now
Perhaps Esmya would have had a better chance of approval in the past, despite its safety issues, owing to a dearth of options for uterine fibroids.
But elagolix looks to have approval secured, especially as Abbvie today reported positive topline results from an extension study, Elaris UF-Extend, evaluating 12 months of elagolix at 300mg twice daily – higher than the approved endometriosis dose – plus hormone add-back therapy. Add-back therapy is needed to counteract the menopause-like symptoms that result from full oestrogen suppression with GnRH agonists.
|The uterine fibroid treatment landscape|
|Annual indication sales ($m)|
|Product||Company||Pharma class||Indication status||2018e||2020e||2022e||2024e|
|Elagolix||Abbvie||GnRH antagonist||Phase III||-||204||477||636|
|Linzagolix||Obseva||GnRH antagonist||Phase III||-||-||51||191|
|Esmya||Allergan/Gedeon Richter||SPRM||Approved in EU, CRL in US||119||169||173||183|
The treatment landscape is set to change further in the next few years: other therapies on the horizon include Obseva’s linzagolix, which is due to yield phase III fibroid data next year.
Before the liver concerns hit Esmya, the product had been forecast to bring in around $550m by 2022, putting it almost on par with elagolix. Since then, though, sellside consensus has gone into freefall.
Private equity might still be interested in Allergan’s women’s health offering – but probably not at the price the company would have liked.
|Selected phase III uterine fibroid trials|
|Project||Company||Study||Trial ID||Data due|
|Source: EvaluatePharma, clinicaltrials.gov.|