Early knockback for AbbVie as FDA rejects Allergan eye drug

AbbVie’s $63bn takeover of Allergan was always more about cash flow than extending its pipeline, but an FDA rejection of one of the latter’s late-stage drugs will nevertheless be a blow.

The US regulator issued a complete response letter (CRL) for abicipar pegol, the lead drug in Allergan’s alliance with Molecular Partners on a new class of protein therapeutics the companies call DARPins, short for designed ankyrin repeat proteins.

Abcipar pegol targets VEGF, and was compared to Novartis’ established anti-VEGF antibody Lucentis (ranibizumab) in a pair of head-to-head phase 3 trials in patients with wet or neovascular age-related macular degeneration, a major cause of blindness.

The data showed that the drug was as effective as Novartis’ drug, with less frequent dosing, but was associated with more side effects, including inflammation of the eye in around 9% of recipients, with 1,6% of patients reporting severe symptoms.

That finding on tolerability has scuppered Allergan and Molecular Partners’ FDA filing, it seems, as the CRL “indicates that the rate of intraocular inflammation observed following administration of abicipar pegol…results in an unfavourable benefit-risk ratio” when used to treat wet AMD, according to AbbVie.

AbbVie said it would meet with the FDA to work out the next steps with the drug. Head of ophthalmology Michael Robinson said: “We continue to believe in the need for treatment options that provide patients with reliable vision gains and less frequent dosing.”

Abcipar pegol was given every two or three months in phase 3 testing, which compares to monthly dosing with Lucentis and Bayer’s rival anti-VEGF drug Eylea (aflibercept), which is initially given once a month and then later every two months.

Allergan has previously said it estimated abicipar pegol could become a $1.5bn product at peak thanks to the advantage of dosing every three months, given that injections for wet AMD are administered directly into the eye, making it one of its brightest late-stage prospects.

Analysts think the inflammation issue will, however, reduce that sales potential markedly, even if the drug eventually gets approved.

Meanwhile, Novartis recently claimed approval for Beovu (brolucizumab), a VEGF antibody dosed every three months that improved on Eylea’s efficacy in a comparative trial.

Beovu got off to a quick start in the market but has also been hit by reports of intraocular inflammation which resulted in a warning added to the drug’s labelling in the US earlier this month.

According to the update, Beovu is associated with a 4% rate of intraocular inflammation and a 1% rate of retinal artery occlusion – which can threaten eyesight. Analysts at Jefferies have said the safety issue could halve their earlier prediction of $2.5bn in peak sales for the drug.