FDA Approves First Interchangeable Biosimilar to Adalimumab, Plus a Combination Drug Approved

First Interchangeable Biosimilar to Adalimumab Approved

In October, the U.S. Food & Drug Administration (FDA) approved the supplemental biologics license application for Cyltezo (adalimumab-adbm), making it the first biosimilar to be interchangeable in the U.S. with Humira (adalimumab), its biologic reference product.¹

Adalimumab-adbm was originally approved by the FDA in August 2017 as a biosimilar to adalimumab for the treatment of the same chronic inflammatory diseases as adalimumab, including rheumatoid arthritis (RA), ankylosing spondylitis, juvenile idiopathic arthritis (JIA) and psoriatic arthritis and has now obtained interchangeable status for these approved indications.² Thus, the biosimilar may be substituted for the reference product adalimumab at the pharmacy without the prescriber’s intervention.

Individual state laws control how and if physicians will be notified of this switch.³ In Hawaii, for example, H.B. 254 requires biosimilar substitution for the reference product if, “1) The prescriber does not prohibit substitution; 2) the prescriber and patient consent to the substitution; and 3) the substitution results in a financial savings to the consumer or ultimate payer (including third party payers).”⁴ In Indiana, S.B. 262 requires the prescriber to indicate the biosimilar may be substituted. However, under H.B. 365, Florida only requires the prescriber hasn’t expressed a preference against it and requires notification only of the person presenting the prescription, not necessarily the patient, and not the provider.⁴

Biosimilars are highly similar to and have no clinically meaningful differences related to safety, effectiveness and pharmacokinetics from their FDA-approved, biologic reference product. An additional post-marketing study is required to obtain interchangeable status. The proposed interchangeable product is expected to produce the same clinical result as the reference product in any given patient, and for a product administered more than once to an individual, switching between the proposed interchangeable product and the reference product must not increase safety risks or decrease effectiveness compared to using the reference product without such switching between products. The study on which the FDA approval of the supplemental biologics license application for Cyltezo (adalimumab-adbm) was based compared adalimumab-adbm with adalimumab in patients with plaque psoriasis. Important note: The interchangeable status applies to all indications for which the reference product is approved, not just psoriasis.

The FDA approval for interchangeability of adalimumab-adbm for adalimumab was supported by data from the phase 3, randomized, double-blind, parallel-arm, multiple-dose, active comparator VOLTAIRE-X trial (NCT03210259), which studied the effects of multiple switches between adalimumab and adalimumab-adbm.

At study initiation, patients (n=238) with moderate to severe chronic plaque psoriasis received a loading dose of 80 mg of subcutaneous adalimumab (i.e., two prefilled syringes of 40 mg injection/0.8 mL). Next, patients were randomized to switch to adalimumab-adbm or continue treatment with adalimumab. Baseline characteristics of participants were generally well balanced between the different treatment groups.⁵