Alvotech Lines Up US Biosimilar Approvals After FDA Inspection

A longtime headache for Alvotech could soon be over, after a US Food and Drug Administration reinspection of its biosimilar production plant in Reykjavik seemingly cleared the way for the agency to approve US rivals to Humira (adalimumab) and Stelara (ustekinumab) that have previously been held back by complete response letters issued due to manufacturing deficiencies.

FDA approval of the adalimumab biosimilar is now anticipated by Alvotech on 24 February 2024, with approval for the ustekinumab biosimilar to follow on 16 April 2024.

Alvotech and US marketing partner Teva have for some time been seeking approval for their AVT02 100mg/ml adalimumab biosimilar, with the proposed high-concentration interchangeable product boasting a combination of attributes that the firms believe could make it a market leader (see sidebar).

However, a series of CRLs linked to deficiencies observed by the FDA at the Reykjavik facility have prevented the companies from gaining approval, blocking them from a fiercely competitive market in 2023 that saw multiple Humira biosimilars hit the US simultaneously. (Also see "Alvotech And Teva To Miss US Adalimumab Launch After Further FDA Setback" - Generics Bulletin, 29 Jun, 2023.)

The FDA has previously indicated that AVT02 can be approved as an interchangeable adalimumab biosimilar based on the data provided in Teva and Alvotech’s filing, providing the Reykjavik facility passes muster. (Also see "FDA Promises Interchangeability For Alvotech’s 100mg/ml Humira Rival – If It Passes Inspection" - Generics Bulletin, 22 Dec, 2022.)

Similarly, Alvotech and Teva’s partnered AVT04 ustekinumab biosimilar has also previously been knocked back pending FDA reinspection of the Reykjavik plant – although US approval for this product is somewhat less time-sensitive given that the firms do not plan to launch until early 2025, under a settlement. (Also see "Alvotech Receives CRL From FDA Over Ustekinumab Filing" - Generics Bulletin, 12 Oct, 2023.)

Other ustekinumab biosimilar launches are also slated for early 2025, with Amgen so far the only company to win an FDA approval.  (Also see "Trailblazer Amgen Scoops First US Stelara Biosimilar – With Interchangeability" - Generics Bulletin, 1 Nov, 2023.)

Alvotech had recently indicated that an FDA inspection of the Reykjavik plant was scheduled for 10-19 January 2024, with the firm underlining that “inspection status of our manufacturing facility is the only outstanding requirement in order to gain approval for both of these applications in the US.” (Also see "Golimumab Results Lead Off A Raft Of Updates For Alvotech" - Generics Bulletin, 13 Dec, 2023.)

Alvotech founder, CEO and chairman Robert Wessman had previously explained that the firm had been “addressing all the observations we got from the previous inspection” and believed that “we have answered those already in our previous answers to FDA. But likely is that those answers will be reviewed once an inspection happens on site.”

“We have been, of course, using the time very well since the last inspection,” Wessman indicated late last year. “And we believe, based on that effort and the resources we have put into the quality system and the people and training, that we are in a good place to receive the FDA in January.”

And now, Alvotech has revealed that “following the FDA inspection, Alvotech received a Form 483 [notice of deficiencies] with one observation,” adding that “Alvotech expects to provide the FDA with a response in the following days.”

“We believe that the observation is readily addressable, and we intend to respond as quickly as possible,” indicated Wessman.

As such, the firm said that “based on the conclusion of the facility reinspection, Alvotech believes it is in a position to receive approval in the US for AVT02 and AVT04 by 24 February 2024 and 16 April 2024, their respective goal dates.”