In December, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) started a review of the treatment for abnormal bleeding in women with uterine fibroids after four cases of serious liver injury – three resulting in a liver transplant – were reported among users of the drug.
Esmya (ulipristal acetate) is a selective progesterone receptor modulator billed as a safer and more effective pharmacological treatment for uterine fibroids than existing drugs such as AbbVie’s Lupron (leuprolide acetate), a synthetic gonadotropin-releasing hormone (GnRH). It was approved by the EMA in 2012, and Gedeon Richter’s US partner Allergan is currently awaiting approval in the US.
“The advice is that no new treatment courses should be prescribed until further notice,” said the Medicines and Healthcare products Regulatory Agency (MHRA) in a statement. “Those who are already taking Esmya or have recently stopped, it is advisable that they have blood tests to monitor their liver function at least once a month whilst taking the medicine.”
The European regulatory actions come as Allergan is in the midst of an FDA review of its New Drug Application (NDA) for Esmya, which is scheduled for a verdict in May of this year. In Canada, the regulatory authority has asked for the product’s label to be amended to note the liver injury cases.
Allergan’s chief R&D officer David Nicholson said during the company’s fourth-quarter results call earlier this month that the company “has not seen evidence to suggest that there is a causal relationship between Esmya and liver injury, and indeed no cases of liver injury were observed in controlled clinical trials”.
“The tox studies were clean, the controlled clinical trials were clean [and] about 700,000 patients have been exposed to Esmya worldwide with only four severe cases of liver injury reported.”
He added that Allergan is helping its European partner for Esmya, Gedeon Richter, with the internal and external analyses of the benefit/risk profile of Esmya, and noted that the FDA has been informed of the European post-marketing findings.
“So far, we have no reason to believe that the approval of Esmya is going to be delayed by the deliberations in Europe,” said Nicholson.
Allergan has said that it sees Esmya as a flagship brand for its women’s health unit, which remains a core focus for the group despite suggestions that company could benefit from spinning it out. There’s no sign of that for now – Allergan bolstered its female health pipeline towards the end of last year with a deal to buy Repros and a late-stage drug for uterine fibroids and endometriosis.
Analysts have suggested that Esmya could be an $800m product for Allergan if it secures US approval. It’s a generous estimate, given that Gedeon Richter said recently it recorded €93m sales for the product in 2017, up from €69m in the prior year, mainly from the top 15 EU countries
