FDA Approves Simlandi, a Citrate-Free, High-Concentration, Interchangeable Biosimilar to Humira

The Food and Drug Administration (FDA) has approved Simlandi (adalimumab-ryvk), a citrate-free, high-concentration, interchangeable biosimilar to Humira^® (adalimumab).

Simlandi, a tumor necrosis factor (TNF) blocker, is indicated for:

• Rheumatoid arthritis (RA): Reducing signs/symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA; may be used alone or with methotrexate (MTX) or other non-biologic DMARDs.
• Juvenile idiopathic arthritis (JIA): Reducing signs/symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older; may be used alone or with MTX.
• Psoriatic arthritis (PsA): Reducing signs/symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA; may be used alone or with non-biologic DMARDs.
• Ankylosing spondylitis (AS): Reducing signs/symptoms in adult patients with active AS.
• Crohn disease (CD): Treating moderately to severely active CD in patients 6 years of age and older.
• Ulcerative colitis (UC): Treating moderately to severely active UC in adult patients.
• Plaque psoriasis (PsO): Treating adult patients with moderate to severe chronic PsO who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.
• Hidradenitis suppurativa: Treating moderate to severe hidradenitis suppurativa in adults.
• Uveitis: Treating non-infectious intermediate, posterior, and panuveitis in adults.

Simlandi is an interchangeable biosimilar and can be substituted for the reference product without requiring a prescription change. The approval of Simlandi was supported by data from a phase 1 pharmacokinetics similarity study (AVT02-GL-101; ClinicalTrials.gov Identifier: NCT03849313), a phase 3 comparative efficacy and safety study (AVT02-GL-301; ClinicalTrials.gov Identifier: NCT03849404), and a phase 3 switching study (AVT02-GL-302; ClinicalTrials.gov Identifier: NCT04453137).

The phase 1 study compared the pharmacokinetics, safety and tolerability of Simlandi to Humira at a single dose of 40mg in 392 healthy adults. Results showed no clinically meaningful differences between Simlandi and Humira.

The AVT02-GL-301 study compared the efficacy, safety, and immunogenicity of Simlandi to Humira in 413 adults with moderate to severe chronic plaque psoriasis. Patients were randomly assigned 1:1 to receive Simlandi or Humira with an initial loading dose of 80mg subcutaneously, followed by 40mg once every other week until week 48.

Findings showed Simlandi met the primary end point achieving therapeutic equivalence to Humira as measured by the Psoriasis Area and Severity Index percent improvement at week 16. Moreover, there were no clinically meaningful differences between Simlandi and Humira on the secondary endpoints, including safety, tolerability, immunogenicity and serum trough levels at steady state through the entire study duration.

In AVT02-GL-302, patients with moderate to severe chronic plaque psoriasis (N=568) were randomly assigned to either continue Humira or continue receiving alternating doses of Simlandi and Humira for an additional 16 weeks, after completing a 12-week lead in period with Humira. Findings demonstrated bioequivalence of repeated switches between Humira and Simlandi to Humira administration without switching.

Simlandi is supplied as a 40mg/0.4mL prefilled single-dose autoinjector in 1- and 2-count cartons. The product is expected to be launched imminently in the US.