Data on Adalimumab Biosimilar Confirm Equivalence of Low- and High-Concentration Formulations

While 2023 is becoming known as an important year for biosimilars because of the introduction of at least 7 adalimumab (Humira) biosimilars in the United States, there are nuances with the formulation of adalimumab that are important to consider.

All 7 approved biosimilars are based on the low-concentration version of the reference product; however, the high-concentration version has the most market share. A new abstract presented at EULAR 2022, the annual congress of the European Alliance of Associations for Rheumatology, compares the pharmacokinetics (PK) equivalence of a low-concentration SB5 (SB5-LC; Hadlima from Samsung Bioepis) with a high-concentration version (SB5-HC).

The phase 1 clinical trial compared SB5-LC (40 mg/0.8 mL) with SB5-HC (40 mg/0.4 mL) in healthy male subjects. The trial was a randomized, single-blind, 2-arm, parallel group, single-dose study, and it demonstrated PK equivalence between the 2 formulations.

“The addition of new data to our adalimumab biosimilar, SB5 is great news for patients with rheumatic and other inflammatory diseases,” Donghoon Shin, vice president and medical & lifecycle safety team leader at Samsung Bioepis, said in a statement.

A total of 188 subjects were randomized 1:1 to receive a single subcutaneous injection of either SB5-HC or SB5-LC and subsequently observed for 57 days. One subject was excluded from the PK analysis for a total of 187 analyzed (93 in SB5-HC vs 94 in SB5-LC).

The geometric least squares means ratios for area under the concentration-time curve from time zero to infinity and maximum serum concentration were 0.920 for SB5-HC and 0.984 for SB5-LC with corresponding 90% CIs within the pre-defined equivalence margin “indicating the two treatment groups are bioequivalent,” the researchers wrote.

As for the safety of SB5-HC vs SB5-LC, the study had no deaths or serious adverse events, and no subject discontinued the study due to treatment-emergent adverse events (TEAEs). The groups experienced similar TEAEs with 44.7% receiving SB5-HC and 51.1% receiving SBR-LC experiencing TEAEs. The most frequent TEAE was headache for 10.6% of SB5-HC and 12.8% of SB5-LC.

“This study demonstrated PK equivalence between SB5-HC and SB5-LC in healthy subjects,” the researchers concluded. “Both SB5-HC and SB5-LC were generally well tolerated with similar safety profiles.”

While there are no FDA-approved high-concentration adalimumab biosimilars, there are 2 that may come to market in 2023: Celltrion’s Yuflyma and Alvotech’s AVT02. Although these biosimilars are not approved by the FDA, both companies entered an agreement with AbbVie, the maker of the reference product, for the products to come to market.

Applications for both Yuflyma and AVT02 have been submitted to the FDA. Yuflyma is already approved and available in Canada and Europe.

The high-concentration formulations are also citrate-free, which means they cause less pain at the injection site after administration.

At the Asembia Specialty Pharmacy Summit in early May, speakers explained that having biosimilar versions of the high-concentration formulation is key so payers do not need to develop plans to move approximately 85% of the market from the new formulation back to the old formulation.

“Instead of this big hurdle and messy conversion…now, we're going to have both the old formulation and new formulation of adalimumab,” said Jeffrey Casberg, MS, RPh, vice president of pharmacy at IPD Analytics, LLC, during his session at Asembia.

Reference

Ahn SS, Lee M, Baek Y, Lee S. A randomized phase I pharmacokinetic study comparing high-concentration, low-volume, and citrate-free SB5 (40 mg/0.4 mL) with prior SB5 formulation, and adalimumab biosimilar, in health male subjects. Presented at: EULAR 2022; June 1-4, 2022; Copenhagen, Denmark. Abstract POS0641.