US approval of Alvotech’s Humira (adalimumab) biosimilar could be delayed by six months after the FDA found further issues at a manufacturing facility in Reykjavik, Iceland.

Thanks to a 2017 settlement with AbbVie, Amgen launched the first biosimilar of best-selling monoclonal antibody Humira earlier this year. At the end of next month, up to nine more biosimilars could be competing for a slice of the $18.6 billion market.

Iceland-based firm Alvotech has two separate applications for AVT02, with the first Biologics License Application (BLA) having the data supporting biosimilarity to Humira and the second having the data supporting biosimilarity and additional data seeking interchangeability.

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VadimVasenin

However, Alvotech may miss out on a June launch after the US Food and Drug Administration (FDA) issued a second complete response letter (CRL) relating to its candidate AVT02 last month.

“Alvotech hosted an inspection that concluded on March 17 of this year,” Alvotech CEO Robert Wessman said on his firm’s recent Q1 conference call. “The company provided substantive response to the 483s on April 3rd. The biosimilar BLA received a complete response letter from FDA on April 13 of this year, noting only that the deficiency from the recent inspection needed to be resolved. The interchangeable BLA has a goal date of June 28th of this year.”

The inspection, 483, and subsequent CRL follows a prior inspection in March 2022, which resulted in the issuance of an earlier CRL noting “certain deficiencies” in the manufacturing of AVT02.

According to the firm, there were no repeat observations highlighted in the March 2023 inspection, which instead found issues with the quality system and the quality units.

“Our responses to the 483 included certain commitments and we agreed to provide the FDA with monthly updates on the progress of these commitments,” said Wessman. “This was done on May 1st of this year and we intend to provide another one on June 1st, which, in our view, will complete outstanding corrective and preventive actions that we were committed to.

“Subsequent to that, the company intends, as a matter of procedure, to resubmit the biosimilar BLA, which would trigger a six month review period that would be needed in case approval is not granted on June 28th, which, again, is the goal date for the interchangeable BLA.”