Alvotech Achieves Milestone in Bid to Capture Adalimumab Share

June 18, 2021

Getting to the stage where clinical data on interchangeability are reportable to the FDA is a key milestone in Alvotech’s bid to get its high-concentration adalimumab biosimilar approved and on the market.

Reykjavik, Iceland–based company Alvotech believes it has obtained the data it needs to convince the FDA to award an “interchangeable” designation for its high-concentration, citrate-free biosimilar candidate (AVT02) for adalimumab.

AVT02 (100 mg/mL) is one of the key drugs in Alvotech’s drug pipeline. Being citrate free, it causes less pain upon injection and has potentially greater acceptance by patients and health care practitioners. The originator company (AbbVie) has already captured significant market share in the United States and Europe with the high-concentration version of adalimumab it introduced in 2018.

The interchangeability designation would constitute an additional differentiator for AVT02. This would allow pharmacists to fill prescriptions with the biosimilar without first having to obtain authorization from a prescribing physician.

Alvotech’s Switching Study

Obtaining an interchangeable designation requires a successful switching study demonstrating that no significant clinical differences or risks in safety and efficacy arose despite multiple switches between the biosimilar candidate and the reference product.

On June 15, Alvotech reported a major milestone in the switching study (N = 568) for AVT02. In the first phase of the study, all patients received Humira. In the just-completed second phase, 1 cohort of patients continued to receive Humira and a second cohort switched between AVT02 and Humira. Alvotech reported that it has finished the second phase.

Completion of the second phase, at week 28 of the study, enables Alvotech to collect final data for primary outcome measures of the study. The study, AVT02-GL0302, is evaluating the pharmacokinetics (PK), safety, efficacy, and immunogenicity of AVT02.

“The completion of the comparative treatment phase of the switching study is a key milestone in our program for our AVT02 interchangeable biosimilar candidate. Achieving interchangeability in the United States is a cornerstone in our development strategy and consistent with our commitment to patients,” Mark Levick, CEO of Alvotech, said in a statement.

Top-line results for the switching study are expected to be reported later this year, the company said. Still to come is the third, open-label phase in which all patients receive AVT02.

Alvotech has applied in the United States and the European Union for approval of AVT02. The company anticipates an FDA decision on the US biologics license application for this product in September 2021 and a European Medicines Agency decision in the fourth quarter of 2021.

In the event of product approvals, however, the exact timing of a market launch will depend on the outcome of litigation between Alvotech and the originator company, AbbVie. The 2 companies have gone to court over the validity of patents governing Humira and whether Alvotech fairly and honestly obtained its technical knowledge of adalimumab production.

Alvotech states that it is the only biosimilar developer so far to seek an interchangeable designation for high-concentration adalimumab. However, it is not the only biosimilar developer to seek an interchangeable designation for an adalimumab formulation.

Boehringer Ingelheim recently reported results from VOLTAIRE-3, a phase 3 randomized study comparing PK for Cyltezo (40 mg/0.8 mL) and the respective adalimumab formulation from AbbVie. Cyltezo was approved in August 2017 and is scheduled for launch in 2023, according to an out-of-court settlement between AbbVie and Boehringer Ingelheim.

Boehringer Ingelheim stated that it was the first, to its knowledge, to report findings that it anticipated would meet FDA requirements for an interchangeable designation—any type of interchangeable biosimilar, not just an adalimumab interchangeable. The FDA has approved 29 biosimilars so far.