FDA rejects Allergan's fibroids drug, citing liver safety concerns

The Food and Drug Administration (FDA) has rejected Allergan’s treatment for uterine fibroids, ulipristal acetate, citing safety concerns raised from post-marketing reports outside the US market.

The drug is already marketed in Europe for the treatment of uterine bleeding in women with fibroids under the brand name of Esmya.

But earlier this year the European Medicines Agency (EMA) recommended safety measures to minimise the risk of rare but serious liver injury with the drug.

Allergan asked the FDA to approve ulipristal acetate for abnormal uterine bleeding in women with uterine fibroids.

In its dreaded Complete Response Letter, the FDA said it could not approve ulipristal acetate in its current form and is requesting further information about its safety.

Allergan said it plans to meet with the FDA to discuss its comments and the next steps.

The company noted that its filing included results from two phase 3 clinical trials, and all phase 3 registration studies, as well as real-world data in more than 700,000 women with uterine fibroids across 80 countries worldwide.

Safety measures

Safety measures announced by European regulators in May include a contraindication in women with known liver problems, liver tests before, during and after stopping treatment, and a card to inform them about the need for liver monitoring.

Use of the medicine for more than one treatment course has been restricted to women who are not eligible for surgery.

There have been eight cases of serious liver injury in the 765,000 patients treated so far, and the EMA said it was possible that Esmya may have contributed.

Safety regulators from the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) made the recommendations following reports of serious liver injury, including liver failure leading to transplantation.

The PRAC also recommended that studies should be performed to determine the effects of Esmya on the liver, and whether the new measures are effective in minimising its risks.

Ulipristal acetate has been approved in the US in a different formulation for emergency contraception since 2010, marketed by HRA Pharma under the brand name ella.

The drug is a selective progesterone receptor modulator (SPRM), which acts directly on the progesterone receptors in three target tissues: the endometrium (uterine lining), uterine fibroids, and the pituitary gland.