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

Interchanging adalimumab-adbm was shown to be equivalent to adalimumab (Humira), with no meaningful clinical differences in pharmacokinetics, efficacy, immunogenicity or safety between the switching and continuous treatment groups. Evaluated were the percentage of patients with a 75% reduction in Psoriasis Area and Severity Index (PASI75) response at week 32, anti-drug antibodies, neutralizing antibodies, minimum and maximum observed concentrations during the dosing interval, physician global assessment and patients with drug-related adverse events.

These results were presented at the American Academy of Dermatology 2021 virtual conference, April 23–25. Similar results supporting interchangeability were also reported in the VOLTAIRE-PSO study (NCT02850965).⁶

Studies from outside the U.S. have shown that other adalimumab biosimilars are also interchangeable with the reference product. These adalimumab biosimilar switching studies have been performed in patients with moderate to severe active RA and JIA. In these studies, adalimumab biosimilars demonstrated no differences in effectiveness, pharmacokinetics, immunogenicity and safety from the reference product.^7-9

Adalimumab-adbm is not yet commercially available in the U.S. The commercial license will begin on July 1, 2023.

New Combination Oral Analgesic

On Oct. 15, the FDA approved a new combination, prescription analgesic that contains a unique co-crystal formulation of celecoxib and tramadol. This formulation provides another option for multi-modal pain management. The product, called Seglentis, will contain 56 mg of celecoxib and 44 mg of tramadol in an oral tablet. A risk evaluation and mitigation strategy (REMS) will be used to encourage the treatment’s safe and appropriate use. It will be available in early 2022.¹⁰

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Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. News release: U.S. FDA approves Cyltezo (adalimumab-adbm) as first interchangeable biosimilar with Humira. Boehringer Ingelheim. 2021 Oct 15.
2. FDA approval letter: Cyltezo (adalimumab-adbm). 2017 Aug 25.
3. FDA-approved biosimilar products. U.S. Food & Drug Administration. 2021 Sep 9.
4. State biosimilar substitution laws. Mintz, Levin, Cohn, Ferris, Glovsky & Popeo PC. 2019 Feb 8.
5. News release: VOLTAIRE-X phase 3 data in patients with moderate to severe chronic plaque psoriasis support interchangeability application. Boehringer Ingelheim. 2021 Apr 23.
6. Menter A, Arenberger P, Balser S, et al. Similar efficacy, safety and immunogenicity of the biosimilar BI 695501 and adalimumab reference product in patients with moderate to severe chronic plaque psoriasis: Results from the randomized phase 3 VOLTAIRE-PSO study. Expert Opin Biol Ther. 2021 Jan;21(1):87–96. Epub 2020 Dec 29.
7. Gall S, Kiltz U, Kobylinski T, et al. No major differences between patients with chronic inflammatory rheumatic disease who underwent mono- or multiswitching of biosimilars in routine care (perception study). Ann Rheum Dis. 2021;80(suppl 1):376.
8. Horneff G, Dressler F, M. Rühlmann M, et al. Experience with adalimumab biosimilar use in clinical practice: data from the German BIKER-registry. Ann Rheum Dis. 2021;80:933–934.
9. Furst D, Keystone E, Kay J et al. Efficacy and safety after transition from reference adalimumab to CT-P17 (adalimumab biosimilar: 100 mg/mL) in comparison with the maintained treatment (CT-P17 or reference adalimumab) in patients with moderate to severe active rheumatoid arthritis: 1-year result. Ann Rheum Dis. 2021;80:1123–1124.
10. News release: Esteve Pharmaceuticals receives FDA approval for Seglentis (celecoxib and tramadol hydrochloride). Kowa Pharmaceuticals America Inc. 2021 Oct 18.