- Allergan plc announced in a tersely worded statement after market's close on Wednesday that the FDA user fee action date for ulipristal acetate has been pushed to August 2018 " to provide time for a full review of the file."
- Allergan did not cite the reason for the delay, but acknowledged to BioPharma Dive that an EU review of potential liver injury accounts for the extended review. The company said in October that the New Drug Application (NDA) had been submitted and accepted by the Food and Drug Administration, and that an approval decision was expected in the "first half of 2018."
- Allergan's stock hit a 52-week low of $148.41 in morning trading on Thursday, well off the 52-week high of $256.80 it hit last July.
Sold as Esmya in Europe and Canada, ulipristal acetate is a treatment for excessive bleeding caused by uterine fibroids.
The European Medicines Agency's Pharmacovigilance Risk Assessment Committee is currently investigating safety issues related to Esmya. In post-marketing surveillance, four cases of severe liver injury were identified in patients taking Esmya. PRAC is currently deliberating on the matter.
Still, company officials last month said they did not see a cause for concern.
"We have 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," said Allergan Chief R&D Officer David Nicholson on the company's fourth quarter earnings call in early February.
He did note that the FDA has been notified of the issue and that Canada has changed the label to reflect the liver injury cases in the post-marketing section of the label. He also said at the time that the company had no reason to believe that the NDA would be delayed due to the deliberations in Europe.
"So look, the pharmacological characteristics of ulipristal, the active ingredient in Esmya, together with all of the non-clinical and clinical data collected from the controlled clinical trials, didn't show any liver toxicity signals on ulipristal. And so the tox studies were clean, the controlled clinical trials were clean. About 700,000 patients have been exposed to Esmya worldwide, and only four severe cases of liver injury were reported," Nicholson added on Feb. 6.
Gedeon Richter, which markets the drug in Europe, said in a statement on Feb. 9 that the PRAC "has initiated the implementation of temporary precautionary measures as a part of its review procedure on" Esmya. The committee recommended that no new patients be treated with Esmya and that women already taking the drug not start another course of treatment. The investigation is expected to be completed in May 2018.
"As the evaluation by PRAC continues, Allergan has provided the FDA updates regarding the ongoing drug safety evaluation and provided an update in January 2018. As a result, the FDA required more time and extended the NDA review," said Allergan in a statement to BioPharma Dive.
Esmya is part of Allergan's women's health portfolio. The unit brought in $258.8 million during the fourth quarter, down from $314.5 million during the same period of 2016. If it makes it to market, it could face competition from AbbVie Inc.'s elagolix, an oral gonadotropin-releasing hormone receptor antagonist. Elagolix is currently pending approval to treat endometriosis and is currently in late-stage testing as a treatment for bleeding caused by uterine fibroids.
The drug is one of the six drugs in Allergan's late-stage pipeline that it dubs its "Six Stars," which analysts estimate could bring in anywhere from $6 to $9 billion in revenue.
Allergan has about $3 billion in revenue under potential threat from generic competition in 2018, and has been working to buffer those potential losses. Adding further to its worries, Mylan announced on Wednesday that it is teaming up with Revance Therapeutics Inc. to develop a biosimilar version of Allergan's money machine Botox (onabotulinumtoxinA).