EMA Safety Panel Recommends Withdrawing Esmya Authorizations
Executive Summary
Marketing authorizations for Gedeon Richter’s Esmya and generic versions are certain to be revoked, after a review by the European Medicines Agency’s safety committee concluded that the uterine fibroids drug “can cause liver injury, including the need for liver transplantation.”
Marketing authorizations in the EU for ulipristal acetate products, including Gedeon Richter’s Esmya brand and generic versions of the uterine fibroids drug, should be revoked, the European Medicines Agency’s safety committee has recommended.
The decision comes six months after the EMA’s Pharmacovigilance Risk Assessment Committee temporarily suspended the product in the EU while the agency carried out a further review of its potential to cause serious liver injury. (Also see "Ulipristal Suspended In EU Pending Further Review" - Pink Sheet, 16 Mar, 2020.)
The PRAC’s review has confirmed that 5mg ulipristal acetate used for the treatment of symptoms of uterine fibroids “can cause liver injury, including the need for liver transplantation,” the EMA stated.
In reaching its decision, the PRAC “considered all the available evidence,” including reported cases of serious liver injury. “Patient and healthcare professional representatives, including experts in gynecology, were also consulted. Since it was not possible to identify which patients were most at risk or measures that could reduce the risk, the PRAC concluded that the risks of these medicines outweighed their benefits and that they should not be marketed in the EU.”
The PRAC recommendations will now be forwarded to the EMA’s Committee for Medicinal Products for Human Use, which will adopt an opinion. The CHMP’s opinion will be sent finally to the European Commission, which will adopt a legally binding decision applicable in all EU member states.
An earlier review by the PRAC in 2018 led to the conclusion that women with liver problems should not take the product and that liver function tests should be carried out before patients begin a treatment course with ulipristal. The committee said treatment should be discontinued in the event of elevated transaminases or symptoms compatible with liver injury. (Also see "Liver Damage Worries Lead To Further EU Restrictions On Richter’s Esmya " - Pink Sheet, 21 May, 2018.)
In December 2019, the EMA was notified of a new case of serious liver injury leading to the need for liver transplantation following exposure to Esmya. “Based on the report, this case further supports the causal association between Esmya and serious liver injury,” the EMA declared at the time.
Ulipristal acetate, the EMA noted, is also authorized as a single-dose medicine for emergency contraception. “This recommendation does not affect the single-dose ulipristal acetate emergency contraceptive – ellaOne and other trade names – and there is no concern about liver injury with these medicines.”
Richter’s Esmya Sales In 2020 ‘A Few Million Euros’
Richter had debuted Esmya in March 2012, rolling out the drug in Germany and the UK. When the PRAC recommended in 2018 that no new patients start taking Esmya until it had completed a safety evaluation, Richter vowed to work with the committee and insisted it “takes patient safety seriously.” (Also see "EMA takes action to bar Richter’s Esmya" - Generics Bulletin, 23 Feb, 2018.)
The European Commission later “opened the way” for Richter to reintroduce Esmya, after adopting an opinion from the CHMP recommending measures to minimize the risk of rare but serious liver injury. (Also see "Commission acts on CHMP Esmya advice" - Generics Bulletin, 10 Aug, 2018.)
As Richter began to relaunch Esmya across EU markets in August and September 2018, collaboration partner Allergan received a complete response letter from the US Food and Drug Administration for its new drug application filing. Esmya has still not been greenlit by the FDA.
Speaking to investors on the Hungarian firm’s second-quarter earnings call last month, Richter’s CEO Gábor Orbán said he expected the company to “make no more than maybe a few million euros worth of sales out of Esmya in this year,” following the EMA suspension in March. (Also see "Gedeon Richter Gearing Up For Denosumab And Tocilizumab" - Generics Bulletin, 25 Aug, 2020.)
Global sales of Esmya in 2017 – the last year before disruptions in the wake of the PRAC’s safety review – climbed by more than a third – 34.8% – to €93.0 million (US$110 million), following strong growth in EU15 markets.
Last year, Alvogen became the first company to register a ‘true’ European generic of Esmya, receiving regulatory clearance in “multiple European countries” after successfully concluding 16 parallel registration procedures. (Also see "Alvogen Targets Esmya With First European Rival" - Generics Bulletin, 16 Apr, 2019.)
Richter had previously registered its own authorized generic via the ‘informed consent’ procedure through which the registration is fully based on the original Esmya dossier.