The FDA on Wednesday accepted Alvotech’s Biologics License Application for AVT02, its high-concentration and interchangeable investigational biosimilar for AbbVie’s Humira (adalimumab).
Wednesday’s news comes after the regulator turned down AVT02’s bid for interchangeability in June 2023, citing in a Complete Response Letter (CRL) “certain deficiencies” at the company’s Reykjavik, Iceland facility that needed to be resolved before another application can be considered. The FDA had issued a separate CRL in April 2023, where it pointed to similar deficiencies as the reason for blocking AVT02’s BLA.
In its resubmission, filed in September 2023, Alvotech included additional Chemistry, Manufacturing and Controls data, which the regulator is considering as a “complete response” to the concerns outlined in previous CRLs. The FDA’s verdict on AVT02 is due on Feb. 24, 2024.
“No deficiencies in our BLA have been noted by the FDA other than those associated with our facility. We now await further guidance from the FDA on timing of a reinspection, which we expect to occur in advance of the BsUFA date,” Alvotech CEO Robert Wessman said in a statement.
In the U.S., AVT02 is a monoclonal antibody that is being proposed as a biosimilar to Humira. It works via a similar mechanism of action and binds to tumor necrosis factor-alpha, preventing it from interacting with its corresponding cell surface receptors. In turn, this helps modulate the inflammatory response that is central to diseases such as rheumatoid arthritis and Crohn’s disease.
AVT02 has been approved in several international markets, including all 27 member states of the European Union, Canada, Saudi Arabia, Australia and the U.K.
Alvotech’s bid to have the biosimilar candidate approved in the U.S. had been marred with manufacturing issues. In March 2022, the company’s facility in Reykjavik got issued a warning letter from the FDA, which flagged several quality control lapses. In particular, the letter pointed to “an unacceptably high number of mold recoveries” in rooms designated for drug manufacturing.
Bacterial contamination had also exceeded acceptable levels, according to the FDA’s investigation. Making things worse were the companies corrective and preventive efforts, which were “inadequate” to ensure that such contaminations could be avoided in the future.
In a follow-up visit a year later, in March 2023, the FDA’s investigator did not detect these issues, suggesting that Alvotech had resolved them.
