Esmya rejection hits Allergan's streamlining

A US FDA complete response letter has dealt Allergan’s hopes of finding a buyer for its women’s health unit a serious blow.

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.

Liver worries

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
Esmya Uterine fibroids SPRM - 126
Cervidil Cervical ripening during labour PGE2 regulator 58 58
Anturol Urinary incontinence  LAMA 34 40
Crinone Female infertility, amenorrhoea Progesterone receptor agonist 41 35
Ella Female contraception SPRM 14 24
Trelstar Endometriosis-associated pain Luteinizing hormone/choriogonadotropin receptor agonist 29 23
Gelnique Urinary incontinence  LAMA 17 17
Oxytrol Urinary incontinence  LAMA 8 8
Minastrin 24 FE Female contraception Oestrogen & progesterone receptor agonist 61 8
Allergan's women's health pipeline
Phase III
Contraceptive Vaginal Ring Female contraception Oestrogen & progesterone receptor agonist - -
Phase II 
Estradiol Capsule Atrophic vaginitis Oestrogen receptor agonist - 25
BotuGel Overactive bladder, urinary incontinence  nAChR antagonist; SNAP25 inhibitor - -
Proellex-V Uterine fibroids  Progesterone receptor antagonist - -
Source: EvaluatePharma.

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
Vilaprisan Bayer SPRM Phase III - - 146 282
Linzagolix Obseva GnRH antagonist Phase III - - 51 191
Esmya Allergan/Gedeon Richter SPRM Approved in EU, CRL in US 119 169 173 183
Leuplin Abbvie/Takeda LHRH analogue Marketed 243 219 200 182
Source: EvaluatePharma.

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
Elagolix Abbvie Elaris UF-I NCT02654054 Reported
    Elaris UF-II NCT02691494 Reported
    Elaris UF-Extend NCT02925494 Reported
Linzagolix  Obseva Primrose 1 NCT03070899 2019
    Primrose 2 NCT03070951 2019
Vilaprisan Bayer Asteroid 3 NCT03400943 2020
    Asteroid 4 NCT03400956 2020
Source: EvaluatePharma, clinicaltrials.gov.

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