AbbVie Returns Abicipar Pegol Rights to Molecular Partners Following FDA Rejection

Compiled and Translated by | Fan Dongdong

Recently, AbbVie announced the termination of its license and collaboration agreement with Molecular Partners for the ophthalmic drug abicipar pegol. AbbVie stated that it will return all rights to abicipar pegol to Molecular Partners.

The collaboration was initially established in 2011 between Allergan and Molecular Partners, when the two companies announced a partnership to develop novel multi-DARPin products, with abicipar pegol emerging as a key outcome of this collaboration. Subsequently, following AbbVie's acquisition of Allergan, the rights to abicipar pegol were transferred to AbbVie.

However, the drug’s development progress fell short of expectations. In June 2020, the Biologics License Application (BLA) for the drug in the treatment of neovascular age-related macular degeneration (nAMD) was rejected by the U.S. Food and Drug Administration (FDA). According to the Complete Response Letter (CRL) issued by the FDA at the time, the rejection of abicipar pegol was related to safety concerns associated with the drug. The FDA stated that “an unfavorable benefit/risk ratio was observed regarding the incidence of intraocular inflammation in patients following administration of abicipar pegol 2 mg/0.06 mL.”

At the time, AbbVie stated that it had planned to meet with regulatory authorities to discuss the path forward for the future regulatory approval of abicipar pegol. Michael R. Robinson, Vice President and Global Therapeutic Area Head, Ophthalmology at AbbVie, also stated, “AbbVie remains confident in the need to provide patients with treatment options that deliver reliable vision gains and reduce the treatment frequency for nAMD. AbbVie is committed to working with the FDA to take appropriate next steps regarding the regulatory approval of abicipar pegol.”

The data submitted in the BLA were derived from two Phase III trials (CEDAR and SEQUOIA). Both trials were conducted in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) and compared the efficacy of abicipar pegol with Genentech’s Lucentis (ranibizumab). The primary endpoint for both trials was the percentage of patients with a change in best-corrected visual acuity (BCVA) from baseline of ≤15 letters at Week 52. Trial results demonstrated that after 6 to 8 injections, the efficacy of abicipar pegol at Week 52 was non-inferior to that of Lucentis administered via 13 injections. Although overall adverse events were similar across all treatment groups, the FDA expressed concerns regarding the safety of the drug.

Just one month after the FDA rejection, AbbVie announced in July 2020 the withdrawal of its marketing authorization applications for the ophthalmic drug abicipar pegol submitted to the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. Abicipar pegol is an anti-angiogenic ophthalmic agent based on DARPin technology, indicated for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). As a vascular endothelial growth factor A (VEGF-A) antagonist, abicipar pegol potently inhibits all relevant VEGF-A isoforms. Compared with the current standard-of-care therapy Lucentis, patients receiving abicipar pegol treatment may benefit from a reduced injection frequency.

Following AbbVie's return of the rights to the ophthalmic drug abicipar pegol to Molecular Partners, the company announced plans to establish a special committee to evaluate and determine the next steps for the development of abicipar pegol. Molecular Partners believes that improvements to its manufacturing process and formulation can overcome the inflammation issues raised by the FDA. Currently, abicipar pegol is under development for the treatment of nAMD and diabetic macular edema (DME). Molecular Partners stated that it will continue to collaborate with AbbVie on the research of other DARPin candidates for ophthalmic diseases.

Age-related macular degeneration (AMD) is an eye disease that causes blurring of central vision. Currently, the common clinical treatments are anti-VEGF injections (commonly used) and photodynamic therapy (PDT). Patrick Amstutz, CEO of Molecular Partners, stated, "For patients with nAMD and DME, there remains a substantial unmet medical need clinically. Compared with existing therapies, Molecular Partners continues to believe that abicipar pegol can provide a differentiated treatment option for these patients." Competitors to Molecular Partners include Regeneron's Eylea (aflibercept) and Genentech's Lucentis. If abicipar pegol ultimately receives approval, it is expected to capture market share.

Reference source:

1.AbbVie Returns Eye Drug Rights to Molecular Partners

2.AbbVie Returns Eye Drug Candidate To Molecular Partners