US-FDA denies approval of Alvotech’s Stelara biosimilar as manufacturing problems at site

The US FDA on October 12th denied to approve Iceland-based Alvotech’s AVT04, which it was proposing as a biosimilar to Johnson & Johnson’s Stelara (ustekinumab), marking the fourth regulatory rejection for the company since last year.Alvotech was expected to introduce biosimilars for top-selling immunology medicines, but repeated manufacturing problems at its Reykjavik plant have delayed the launching programme.In its complete response letter, the US health regulator pointed to deficiencies at Alvotech’s manufacturing facility in Reykjavik, Iceland, which were identified by the US FDA during a site inspection in March 2023.  As the complete response letter made clear, those concerns had not been adequately addressed. Until they are, the application is being held up, says a company statement.According to Alvotech, the US FDA did not flag any other issues with its biologics license application for AVT04, and the company intends to file a resubmission shortly, likely triggering an another six months review cycle period and a new decision date.Based on our latest interactions with the US FDA we are currently expecting that the agency will reinspect our facility in the beginning of next year, according to the company statement, adding the company is aiming to make AVT04 available to patients no later than February 2025.However, problems at the Alvotech Reykjavik plant have held back more than the Stelara biosimilar programme. Alvotech’s biosimilar to AbbVie’s blockbuster arthritis treatment Humira (adalimumab), dubbed AVT02, has been turned down by the US health regulator three times in the past year. The first CRL came in September 2022, when the US FDA flagged certain deficiencies that it documented at the  manufacturing site during a March 2022 inspection.In a warning letter at the time, the US FDA’s investigators detected “an unacceptably high number of mold recoveries” in drug manufacturing rooms, along with high levels of bacterial contamination. The plant also had put in place “inadequate” corrective and preventive measures to prevent similar contaminations from happening in the future, according to the regulator.US health regulator’s report points out that the Iceland campus has not been effective in carrying out its duties of ensuring that drug products are manufactured in accordance with current good manufacturing practices to ensure safety, efficacy, purity, and overall quality of drug substances.The US health regulator rejected AVT02’s BLA for the second time in April 2023, also due to manufacturing issues at the Reykjavik plant. The third complete response letter came just months later, in June 2023, blocking the biosimilar’s bid for interchangeability.

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