HD203 Biosimilar is Clinically Equivalent to Etanercept

A “biosimilar” form of etanercept is clinically equivalent to the branded form for rheumatoid arthritis, according to data presented here at the meeting of the American College of Rheumatology. The new drug, called HD203, was approved for use in South Korea on November 11, 2014.

In results from a randomized trial presented here, HD203 showed equivalent efficacy and safety to “reference etanercept” (Enbrel), a widely used TNF-alpha inhibitor.

HD203 is manufactured by the same process as reference etanercept, and has the same amino acid sequence and structure, according to lead author Sang-Cheol Bae, MD, of Hanyang University Hospital in Seoul, South Korea.

According to the US Food and Drug Administration, a biological product is bioequivalent to a reference product if “the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and… there are no clinically meaningful differences in terms of safety, purity, and potency.” They are distinguished from generics, which have simpler chemical structures, and are considered identical to their reference compounds.

“Extensive pharmacokinetic studies have been performed, and head-to-head analyses support the bioequivalence of the two molecules,” Bae said, laying the foundation for the clinical trial.

In the trial, 269 RA patients were randomized 1:1 to receive HD203 or the reference etanercept, both at 25 mg SC twice weekly, along with methotrexate, for 24 weeks. The proportion of patients achieving ACR20 at 24 weeks was the primary endpoint.

Two hundred thirty-three patients were treated according to protocol: 115 on HD203 and 118 on reference etanercept. Approximately 82% of patients in both groups achieved ACR20, with no significant difference between the groups. No differences were seen on the set of secondary endpoints, including ACR50 and ACR70 at 24 weeks, or any of the three response measures at week 12 or week 48, during an extension phase.

Additionally, the two treatments were equivalent in their effects on disease activity at 24 weeks, and response rate measured by the EULAR score, a combination of clinical measures.

Adverse events, serious adverse events, and withdrawal due to adverse events were also equivalent between the two treatment arms.

Eight patients taking HD203 and 3 patients taking the reference etanercept developed “mostly transient” anti-drug antibodies, Bae said.

“In addition to the previously generated analytical, non-clinical and clinical data, this study confirms the biosimilarity of HD203 and reference etanercept,” he concluded.

No information was available on whether HD203 will be offered at a lower price than the currently marketed formulation. HD203 is manufactured by Hanwha Chemical Corporation of South Korea.