A Year After FDA Rejected Abicipar, AbbVie Gives It Back to Molecular Partners

FDA Rejected AbiciparIn the summer of 2020, shortly after the US Food and Drug Administration issued a negative Complete Response Letter to AbbVie and Molecular Partners, rejecting their investigative abicipar pegol candidate to treat exudative retinal disease, both companies said they were committed to pursuing development of the drug.
Now Molecular Partners (MP) may have to go it alone. The company reported last week that AbbVie terminated their collaboration agreement to develop and commercialize what the retina community commonly refers to as abicipar.

The news hasn’t had a great impact on MP’s stock price. It’s been hovering between $18 and $19 a share, just short of the $19.65 price the company’s American depository shares opened at on June 16, but right around its average before AbbVie terminated the deal.

Confidence in Abicipar’s ‘Potential’

And, so far, MP seems determined to pursue the candidate to treat neovascular, or wet, age-related macular degeneration and diabetic macular edema. “There remains a significant unmet medical need for patients living with nAMD and DME, and we remain confident in abicipar’s potential to offer these patients a differentiated treatment option over existing therapies,” MP CEO Patrick Amstutz stated in a press release. “Our focus for this program will be determining the best path to value creation within the context of our expansive portfolio of antiviral and immuno-oncology therapies in development.”
Abicipar is one of a new class of drugs called DARPin therapies. DARPin stands for designed ankyrin repeat protein. DARPin molecules have a high-binding affinity, low molecular weight, and customizable applications, which, AbbVie said last year “have made them an important investigational class of binding protein for researchers.”
With abicipar back completely in its fold, MP said it will form a special committee to evaluate the program and determine next steps.

AbbVie’s 360 Turn

AbbVie’s latest move represents a 360-degree turnaround from last year after the FDA issued the CRL. The CRL indicated that the rate of intraocular inflammation observed following administration of abicipar 2mg/0.05 mL resulted in an unfavorable benefit-risk ratio in the treatment of nAMD. AbbVie also withdrew its regulatory application with the European Medicines Agency (EMA) for abicipar in nAMD. At the time, AbbVie said it planned to meet with the FDA and EMA to discuss their comments and determine next steps.

Abicipar was the subject of two Phase III trials that reported rates of intraocular inflammation of 15.1 to 15.7% in abicipar-treated eyes versus 0 to 0.6% in eyes treated with ranibizumab (Lucentis, Genentech/Roche). The Phase II Maple trial reported an overall 8.9% rate of intraocular inflammation, but all cases responded to treatment.

The FDA’s negative CRL last year came a few months after reports of intraocular inflammation were linked to Novartis’ brolucizumab (Beovu) shortly after the FDA approved the product for treatment of nAMD. Those reports caused a backlash that sharply curtailed the use of Beovu among retina specialists.

“We continue to believe in the need for treatment options that provide patients with reliable vision gains and less frequent dosing for the treatment of nAMD,” Michael R. Robinson, MD, AbbVie VP and global therapeutic area head, ophthalmology, said after the FDA’s announcement. “We are committed to working with the FDA to determine the appropriate next steps for abicipar pegol.”

MP originally licensed abicipar to Allergan in 2011. That original partnership made MP eligible for up to $1.5 billion in various milestone payments. The license transferred over to AbbVie when it acquired Allergan last year.

When AbbVie executed its $63 billion acquisition of Allergan last year, abicipar was one of the drugs expected to make the deal pay off, as a number of financial reporters had noted, among them Max Gelman at Endpoints News.

MP and AbbVie aren’t done with each other, however. They’ll continue to pursue other DARPin candidates for ophthalmic indications, MP stated.