Alvotech’s Stelara Biosimilar Approved in Japan

Alvotech, an Iceland-based pureplay biosimilar manufacturer, announced that its biosimilar referencing Stelara (ustekinumab) was approved for the Japanese market.

The Ministry of Health, Labor and Welfare in Japan is the equivalent of the US FDA. The approval of AVT04 marked the first ustekinumab biosimilar approval for the country and the first product to be approved as part of Alvotech's partnership with Japan-based Fuji Pharma. Source: mhlw.go.jp

AVT04 is the first ustekinumab biosimilar to be approved by the Japanese Ministry of Health, Labor and Welfare. It is also the first biosimilar to be approved under the commercial partnership between Alvotech and Fuji Pharma. Although AVT04 has not been approved in countries outside of Japan yet, dossiers are under review in several major markets, including the United States.

“We are thrilled to receive marketing approval for AVT04 in Japan, which will be Alvotech’s second marketed biosimilar…. Alvotech and Fuji have a joint commitment to increase patient access to vital biologic medicines, and based on our strong partnership, we believe we will be able to serve the growing need for biosimilars in Japan,” commented Robert Wessman, chairman and CEO of Alvotech.

Ustekinumab products are monoclonal antibodies that bind to IL-12 and IL-23 cytokines, which are involved in inflammatory and immune responses. They are used in the treatment of plaque psoriasis and psoriatic arthritis.

AVT04 was developed using an Sp2/0 host cell line and is manufacturers using a continuous perfusion process. The Sp2/0 host cell line allows for more efficient sialylation of the molecule compared with Chinese hamster ovary cells. The Sp2/0 line is also the same type of host cell line used to produce the reference agent.

The partnership between Alvotech and Fuji Pharma concerns AVT04 and 6 other candidates. Under the terms of the partnership, Alvotech is responsible for development and manufacturing and Fuji Pharma has exclusive commercialization rights in Japan. The partnership was established in November 2018.

Update on US Adalimumab Filing

In addition to the approval, Alvotech shared updates on its FDA filing for AVT02, a high-concentration adalimumab biosimilar candidate. Alvotech shared that the FDA has accepted the company’s biologics license application (BLA) resubmission for the drug.

Previously, the product was expected to launch on the US market in July 2023; however, the company received 2 complete response letters from the FDA regarding deficiencies in the manufacturing facility inspection, delaying the regulatory approval and launch of AVT02.

AVT02 is approved in the European Union, Australia, Egypt, United Kingdom, Iceland, Norway, Lichtenstein, Saudi Arabia, and Canada; and Alvotech filed for AVT02 to be approved as an interchangeable biosimilar. The Biosimilar User Fee Act (BsUFA) goal date, representing the deadline for the FDA’s decision, is February 24, 2024.

Wessman expressed pride in the achievement, saying, “We remain committed to bringing AVT02 to patients in the U.S., where the need for a high-concentration, interchangeable biosimilar to Humira remains significant and unmet…. No deficiencies in our BLA have been noted by the FDA other than those associated with our facility. We now await further guidance from the FDA on timing of a reinspection, which we expect to occur in advance of the BsUFA date.”

AVT02 is a monoclonal antibody that references Humira (adalimumab). Adalimumab products are used to treat several conditions, including rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and inflammatory bowel disease (Crohn disease and ulcerative colitis).