Research Focuses on Proposed Adalimumab Biosimilars

Three presentations at this week’s 2017 American College of Rheumatology (ACR) Annual Meeting in San Diego, CA, cover research on pharmacokinetic (PK) equivalence, safety, and switching of 2 proposed adalimumab biosimilars, GP2017 and CHS-1420.

PK, Immunogenicity, and Safety of GP2017

The first study¹, by Julia Jauch-Lembach, MD, and colleagues at Hexal AG and PAREXEL International GmbH, compared the PK, immunogenicity, and safety of Hexal’s proposed adalimumab biosimilar GP2017, EU-authorized adalimumab, and US-approved adalimumab in 318 healthy men. The results of their 3-arm parallel trial show that GP2017 is bioequivalent to EU and US adalimumab, and that EU adalimumab is bioequivalent to US adalimumab. In addition, the researchers said, “There were no clinically relevant differences in safety, tolerability, and immunogenicity among the 3 treatment arms in healthy subjects.”

PK equivalence was demonstrated between GP2017 and EU adalimumab and between EU and US adalimumab by describing the maximum observed serum concentration (C_max) and total area under the curve (AUC_0-inf). Secondary objectives included assessment of AUC_0-360h and AUC_0-last, the comparison of PK parameters between GP2017 and US-adalimumab, and the evaluation of safety, tolerability, and immunogenicity of all 3 products.

The rate of treatment-emergent adverse events (TEAEs) was similar across the GP2017, EU adalimumab, and US adalimumab treatment groups (57.9%, 61.3%, and 58.1%) and all were mild or moderate in severity. Overall, antidrug antibodies (ADAs) were detected in 57.9%, 69.8%, and 69.5% of subjects in the GP2017, EU adalimumab, and US adalimumab groups, respectively, up to day 72.

Long-Term Efficacy Safety and Immunogenicity of GP2017

A second study² reported the findings of Andrew Blauvelt, MD, MBA, of Hexal AG, and colleagues on the long-term efficacy, safety, and immunogenicity of GP2017 compared with reference adalimumab in 465 patients with moderate to severe plaque psoriasis (including 98 with psoriatic arthritis [PsA]).

Initially, patients were randomized to receive GP2017 (n = 231) or reference adalimumab (n = 234). At Week 17, 379 patients were re-randomized to continue treatment with GP2017 (n = 126) or reference adalimumab (n = 127), or to switch between GP2017 and reference adalimumab or vice versa (n = 63 in each group).

There were no clinically meaningful differences in long-term efficacy among patients who received continued GP2017 and reference adalimumab multiple times. Switching was well tolerated; overall safety profiles and immunogenicity rates were similar among individual treatment groups. “The data add to the totality of evidence suggesting GP2017 could be used as a biosimilar for the treatment of the same indications for which reference adalimumab is approved,” the researchers concluded.

Phase 3 Study on CHS-1420

A third study³ on adalimumab reported the findings of Barbara Finck, MD, and colleagues at Coherus BioSciences in a phase 3, randomized, double-blind, multicenter study evaluating the equivalence of the company’s proposed adalimumab biosimilar CHS-1420 to reference adalimumab in 545 adult patients with moderate-to-severe plaque psoriasis, including patients with PsA. The trial demonstrated the equivalence of CHS-1420 to reference adalimumab based on the primary endpoint (75% reduction in the Psoriasis Area and Severity Index [PASI 75] at week 12). Patients who switched from reference adalimumab to CHS-1420 at week 16 had similar efficacy and safety results at week 24 compared with patients who received only CHS-1420 or reference adalimumab. Results in patients with PsA were similar across treatment groups.

PASI 75 was achieved at week 24 by 84.6%, 81.6%, and 88.3% of patients in the CHS-1420 group, the switched group, and the adalimumab group, respectively, demonstrating maintenance of response, the researchers said. No statistically significant difference was found among treatment groups.

TEAEs were reported in 48.9% and 45% of patients in the CHS-1420 and adalimumab groups, respectively, through week 16, and in 20.1%, 19.4%, and 16.3% of patients in the CHS-1420 group, the switched group, and the adalimumab group, respectively, during weeks 17 to 24.

References

1. Jauch-Lembach J, Skerjanec A, Haliduola H, et al. Randomized, double-blind, single-dose, three-arm parallel trial to determine the pharmacokinetics and safety of GP2017, EU- and US-adalimumab in healthy male subjects. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2443. acrabstracts.org/abstract/randomized-double-blind-single-dose-three-arm-parallel-trial-to-determine-the-pharmacokinetics-and-safety-of-gp2017-eu-and-us-adalimumab-in-healthy-male-subjects/.

2. Blauvelt A, Lacour JP, Fowler J, et al. Long-term efficacy, safety and immunogenicity results from a randomized, double-blind, phase III confirmatory efficacy and safety study comparing GP2017, a proposed biosimilar, with reference adalimumab. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2440. acrabstracts.org/abstract/long-term-efficacy-safety-and-immunogenicity-results-from-a-randomized-double-blind-phase-iii-confirmatory-efficacy-and-safety-study-comparing-gp2017-a-proposed-biosimilar-with-reference-adalimum/.

3. Hodge J, Tang H, O’Connor P, Finck B. Switching from adalimumab to CHS-1420: A randomized, double-blind global clinical trial in patients with psoriasis and psoriatic arthritis. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2879. acrabstracts.org/abstract/switching-from-adalimumab-to-chs-1420-a-randomized-double-blind-global-clinical-trial-in-patients-with-psoriasis-and-psoriatic-arthritis/.