FDA Approves Adalimumab-ryvk as Interchangeable Biosimilar for Humira

Adalimumab-ryvk is the first high-concentration, citrate-free biosimilar to Humira that has been granted interchangeability status for the 40 mg/0.4 ml injection.

The FDA approved adalimumab-ryvk (Simlandi; Alcotech, Teva Pharmaceuticals), an interchangeable biosimilar for adalimumab (Humira; AbbVie), for the treatment of adult rheumatoid arthritis, juvenile idiopathic arthritis, adult psoriatic arthritis, adult ankylosing spondylitis, Crohn disease, adult ulcerative colitis, adult plaque psoriasis, adult hidradenitis suppurative, and adult uveitis, according to a press release from Alcotech.¹

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Adalimumab-ryvk is the first high-concentration, citrate-free biosimilar to Humira that has been granted interchangeability status, qualifying for interchangeable exclusivity, for the 40 mg/0.4 ml injection. Thus, adalimumab-ryvk can be substituted for Humira at the pharmacy level without consulting a prescriber, dependent on state laws, according to the press release.¹

"The approval of [adalimumab-ryvk] marks the first high-concentration, citrate-free biosimilar to Humira with [interchangeability] status,” said Eric Hughes, MD, PhD, executive vice president of Global Research and Development and chief medical officer at Teva, said in the press release. "Biosimilars create opportunities for cost savings across the health care system and introduce additional treatment options for patients. This approval marks an important milestone for Teva and Alvotech’s partnership to collaborate on 7 biosimilars and expand the availability, access, and uptake of biosimilars in the [United States.]”¹

The FDA approval was based on evidence including analytical, non-clinical, and clinical data from 3 studies (AVT02-GL-101, AVT02-GL-301, and AVT02-GL-302).¹

About the AVT02-GL-301 Trial

Trial Name: Efficacy, Safety, and Immunogenicity of AVT02 With Moderate-to-Severe Chronic Plaque Psoriasis

ClinicalTrials.gov ID: NCT03849404

Sponsor: Alvotech Swiss AG

Completion Date (Actual): July 2020

AVT02-GL-101 was a phase 1, multicentered, randomized trial used to determine the pharmacokinetic similarities and compare the safety and tolerability of the biosimilar to Humira in healthy adults, according to the press release.¹AVT02-GL-301 (NCT03849404) was a phase 3 multicenter, randomized, control trial used to demonstrate the similar efficacy and compare safety and immunogenicity of the biosimilar compared to Humira in individuals with moderate-to-severe chronic plaque psoriasis. AVT02-GL-302 was a multicenter, randomized, double-blinded study to determine the pharmacokinetic similarities and compare the efficacy, safety, and immunogenicity between those receiving Humira and those switching between the reference and biosimilar products. Individuals included had moderate-to-severe plaque psoriasis, according to the press release.¹

Study participants in AVT02-GL-301 received either the biosimilar or the reference product at 80 mg subcutaneously in week 1, then received 40 mg every other week, according to the study authors. At week 16, the individuals receiving the reference product either randomly continued Humira or received the biosimilar. Those receiving the biosimilar continued with the drug, according to the study authors.²

The primary endpoint in AVT02-GL-301 was percentage improvement in Psoriasis Area and Severity Index (PASI) at week 16 with secondary endpoints including percentage improvements in PASI score at other time points, change from baseline in Dermatology Life Quality Index (DLQI) score, and percent of individuals who had clear or almost clear scores on the Physician’s Global Assessment (sPGA), according to the study authors.²

Investigators included 413 individuals in the study, with 205 randomly receiving the biosimilar and 208 receiving the reference product. For those receiving the biosimilar, the PASI score at week 16 had a percentage improvement of 91.6% compared with 89.6% in those receiving the reference product, according to the study authors. Further, there were comparable patterns in DLQI scores at 11.4-point improvements in the biosimilar group and 10.6-point improvements in the Humira group. For sPGA scores, approximately 90.5% achieved clear or almost clear at week 16, according to the study authors.²

“We strongly believe that biosimilars are important in addressing inflationary pressures in the health care system across all markets, especially in the United States, where biologics represent well over 40% of all pharmaceutical spending. An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the United States,” Robert Wessman, chairman and CEO of Alvotech, said in the press release.¹

References

Alvotech and Teva announce US approval of Simlandi (adalimumab-ryvk) injection, the first interchangeable high-concentration, citrate-free biosimilar to Humira. News release. Alvotech. February 23, 2024. Accessed February 26, 2024. https://investors.alvotech.com/news-releases/news-release-details/alvotech-and-teva-announce-us-approval-simlandir-adalimumab-ryvk
Feldman SR, Reznichenko N, Pulka G, Kingo K, et al. Efficacy, Safety and Immunogenicity of AVT02 Versus Originator Adalimumab in Subjects with Moderate to Severe Chronic Plaque Psoriasis: A Multicentre, Double-Blind, Randomised, Parallel Group, Active Control, Phase III Study. BioDrugs. 2021;35(6):735-748. doi:10.1007/s40259-021-00502-w