FDA Approves Humira Biosimilar Adalimumab-ryvk

Credit: The US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved adalimumab-ryvk (Simlandi), the first interchangeable, high-concentration, citrate-free biosimilar to adalimumab (Humira), according to a press release published by Alvotech and Teva Pharmaceuticals.¹ The tumor necrosis factor (TNF) inhibitor is approved for the treatment of a variety of autoimmune conditions, including rheumatoid arthritis (RA), juvenile idiopathic arthritis, Crohn’s disease, ulcerative colitis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, uveitis, and hidradenitis suppurativa.

The product will qualify for interchangeable exclusivity for the 40 mg/.4 ml injection. Interchangeability allows pharmacists to substitute biosimilars for the originator without prescriber permission, subject to state pharmacy laws. An interchangeable designation requires additional switching studies, ensuring the same clinical outcomes upon interchange and was initially designed to simplify access and accelerate medication availability.²

"The approval of Simlandi marks the first high-concentration, citrate-free biosimilar to Humira with IC status,” Eric Hughes, MD, PhD, the executive vice president global R&D and chief medical officer at Teva said in a statement. "Biosimilars create opportunities for cost savings across the healthcare system and introduce additional treatment options for patients. This approval marks an important milestone for Teva and Alvotech’s partnership to collaborate on seven biosimilars and expand the availability, access, and uptake of biosimilars in the US.”¹

The approval was based on analytical, non-clinical, and clinical data from 3 multicenter, randomized trials which demonstrated the safety, efficacy, and biosimilarity of adalimumab-ryvk compared with the reference product.

The first trial, AVT02-GL-101, was a phase 1 double-blind, 3-arm study which enrolled 550 patients with moderate-to-severe plaque psoriasis and randomized them to receive the reference product (n = 273) or switch to the biosimilar (n = 277). Results revealed the pharmacokinetic similarity and comparable safety and tolerability.³

The next trial was a phase 3, double-blind, parallel-group active control study (AVT02-GL-301), which randomized patients to receive either the proposed biosimilar or adalimumab 80 mg in week 1, then 40 mg every other week. At the 16-week mark, patients receiving the reference product were re-randomized 1:1 to either continue receiving originator adalimumab or switch to the biosimilar until week 48. The objective and subjective efficacy measures showed the biosimilarity between adalimumab-ryvk and the originator through week 50 in both switched and continued treatment cohorts.⁴

The final trial, AVT02-GL-302, enrolled patients with moderate to severe chronic plaque psoriasis and showed persistent efficacy, safety, pharmacokinetics, and immunogenicity between those in the originator cohort and those who underwent repeated switches between adalimumab and the proposed biosimilar. Both those in the adalimumab-ryvk group and the originator group demonstrated comparable percentage improvements in the Psoriasis Area and Severity Index (PASI) score at week 16 (91.6% vs 89.6%, respectively) as well as the static Physician's Global Assessment (sPGA) responses of “clear” or “almost clear” (90.5% in both groups).⁵

“This approval is an important milestone in Alvotech’s journey to offer broader access worldwide to more affordable biologics, following approvals of our biosimilars in other global markets,” noted Robert Wessman, Chairman and CEO of Alvotech. “We strongly believe that biosimilars are important in addressing inflationary pressures in the healthcare system across all markets, especially in the US where biologics represent well over 40 percent 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 US.”¹

Teva Pharmaceuticals partnered with Alvotech in August 2020 for the commercialization of 5 product candidates, including adalimumab-ryvk, in the US. While Alvotech oversees the development and manufacturing of the biosimilar, Teva is focused on the sales and marketing infrastructure.

References

1. ^{Alvotech and Teva announce U.S. approval of SIMLANDI® (adalimumab-ryvk) injection, the first interchangeable high-concentration, citrate-free biosimilar to Humira®. Teva Pharmaceutical Industries Ltd. - Alvotech and Teva Announce U.S. Approval of SIMLANDI® (adalimumab-ryvk) injection, the first interchangeable high-concentration, citrate-free biosimilar to Humira®. February 23, 2024. Accessed February 26, 2024. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2024/Alvotech-and-Teva-Announce-U.S.-Approval-of-SIMLANDI-adalimumab-ryvk-injection-the-first-interchangeable-high-concentration-citrate-free-biosimilar-to-Humira/default.aspx.}
2. ^{Pine L. Breaking down barriers: Why biosimilars face resistance in the US market. HCP Live. December 18, 2023. Accessed February 26, 2024. https://www.hcplive.com/view/breaking-down-barriers-why-biosimilars-face-resistance-us-market.}
3. ^{Feldman SR, Kay R, Reznichenko N, et al. Assessing the Interchangeability of AVT02 and Humira® in Participants with Moderate‑to‑Severe Chronic Plaque Psoriasis: Pharmacokinetics, Efficacy, Safety, and Immunogenicity Results from a Multicenter, Double-Blind, Randomized, Parallel-Group Study. BioDrugs. 2023;37(4):551-567. doi:10.1007/s40259-023-00600-x}
4. ^{Feldman SR, Reznichenko N, Pulka G, 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}
5. ^{Feldman SR, Reznichenko N, Pulka G, 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}