Twelve-Month Court Battle Will Delay Adalimumab Biosimilar Launch for Alvotech

A high-concentration, citrate-free biosimilar of adalimumab (AVT02) proposed by Alvotech of Reykjavik, Iceland, would not come to market before October 2022, a year from now, under a court agreement.

Facing litigation from AbbVie, the Lake Bluff, Illinois-based maker of the original adalimumab (Humira), Alvotech has sought to reduce the number of Humira patents it has to fight to get its biosimilar candidate to market in the United States.

In 2020, AbbVie had annual revenues approaching $20 billion for Humira, an often life-changing product approved for chronic inflammatory diseases such as rheumatoid arthritis, Crohn disease, and psoriasis.

AbbVie originally “asserted” or claimed potential infringement of 62 patents related to adalimumab, and Alvotech countered that just 4 adalimumab patents are of substance in the dispute over AVT02.

The District Court for the Northern District of Illinois has denied a motion by Alvotech to have the court venue changed to the Eastern District of Virginia, where the company thought it could get a speedier, more favorable decision.

The court has also whittled down the number of adalimumab patents that will be litigated in this round to 10, vs the 62 that AbbVie asserted and the 4 that Alvotech has contended are appropriate to address.

A scheduling order issued by the court in September 2021 sets forth the procedure for getting to a decision in the case by October 2022. This allows for hearings on the parties’ claims and counter claims about infringement and enforceability of the adalimumab patent portfolio, a discovery process that extends through June 2022, followed by a trial set for most of August 2022.

According to the court document, AbbVie will restrict its case to the 10 patents identified by the court and will await the court’s decision before requesting an injunction to prevent Alvotech from making use of any patented intellectual property related to adalimumab.

The scheduling document also states that Alvotech has “agreed not to launch AVT02 in the United States prior to the issuance of the court’s decision.”

There are multiple biosimilars of adalimumab already approved, although these are lower-concentration products, and settlements between AbbVie and the respective biosimilar companies will prevent any of these biosimilars from coming to market before 2023.

Alvotech proposes to bring a 100 mg/mL, citrate-free version of adalimumab to market to capitalize on the growing market dominance of this concentration that AbbVie enjoys almost exclusively.

Adalimumab can cause a severe, burning sensation upon administration, which patients may have to endure with multiple monthly injections. Citrate is used to stabilize the pH of adalimumab, and the citrate-free version uses a different buffer that doesn’t cause the same burning and pain that patients experience. This can make citrate-free adalimumab much more popular.

Adalimumab biosimilars have encountered fewer market barriers in the European Union, and during the third quarter of 2021, Celltrion Healthcare aimed to launch its own high concentration adalimumab product (Yuflyma) in 7 EU countries.

The company planned to launch Yuflyma in 3 additional EU countries in the fourth quarter of this year. Celltrion has yet to announce a US launch date, and, indeed, has not yet obtained FDA approval for this agent.

Alvotech is seeking an interchangeable designation for AVT02 which it believes would increase the use of the product in the United States. Interchangeability would allow pharmacists to substitute the biosimilar for Humira without consulting the prescribing physician.

Related Development

The US House Judiciary Committee has approved a bill (HR 2884) that would limit the number of patents an originator company could “assert,” or use as grounds for litigation, against a biosimilar developer.

The limits would be contingent on the biosimilar company’s compliance with information exchanges recommended under the biosimilar approval pathway outlined under the Biologics Price Competition and Innovation Act.

The bill, which has yet to pass the full House or the Senate, would limit the number of patents that could be asserted to 20. An originator’s ability to file suit over patents that were awarded after the date of reference product approval also would be restricted.

The legislation is intended to address the problem of patent “thickets” that represent formidable barriers to companies that want to bring biosimilars to market. Originator companies may have extensive patent portfolios. AbbVie has as many as 136 patents on its adalimumab product which have forced rival companies to settle for delayed market entry pacts with AbbVie rather than risk years of costly litigation.

A recent study by the Biotechnology Innovation Organization (BIO) found that the average number of patents asserted in biosimilar cases is 12, which is well below the 20-patent limit that HR 2884 would impose. However, the number of patents AbbVie has attempted to assert in its case against Alvotech’s proposed adalimumab biosimilar AVT02 vastly exceeds that number.