Shots:

• Dr. Mourad spoke about the acceptance of aBLA for BIIB800, a Tocilizumab biosimilar candidate for several autoimmune diseases, including rheumatoid arthritis
• He briefed about the study design and results from the P-III trial which supported the BLA filing
• This interview focuses on Biogen's notable progress in addressing challenging immunologic conditions, offering potential solutions to help patients confront these complex diseases

Smriti: Discuss the clinical data following the acceptance of the abbreviated Biologics License Application (aBLA) by the U.S. FDA for BIIB800.

Dr. Mourad Farouk Rezk: The BIIB800 clinical program included a Phase 3 multicenter, multinational, randomized, double-blind, parallel-group, active-control global study, designed to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of BIIB800 compared to ACTEMRA® in 621 patients with moderate to severe rheumatoid arthritis with inadequate response to methotrexate. 

The trial met its primary endpoints of ACR20* response at Week 12 and Week 24. The ACR20 response rates in the BIIB800 group and the reference tocilizumab group were 68.97% vs. 64.82% at Week 12, respectively; and 69.89% vs. 67.94% at Week 24, respectively. The estimated differences between the two groups were within the pre-defined equivalence margins (4.15% (95% Confidence Interval [CI] - 3.63 to 11.93) at Week 12 and 1.94% (90% CI -4.04 to 7.92; 95% CI -5.18 to 9.07) at Week 24). 

The results from Week 24 to Week 48 were reported at the 2022 American College of Rheumatology (ACR) Convergence. ACR20/50/70 responses and mean change in DAS28-ESR and DAS28-CRP from baseline were comparable across the treatment groups.

Smriti: Elaborate on how this approval will benefit patients with immune-mediated inflammatory diseases.

Dr. Mourad Farouk Rezk: The data from the Phase 3 comparative clinical trial demonstrated that the biosimilar candidate BIIB800 has equivalent efficacy and a comparable safety and immunogenicity profile to the reference tocilizumab product. If approved, BIIB800 will add to the treatment armamentarium as a high-quality and cost-effective IL-6R inhibitor. Biosimilar offerings have evolved over the last few years to cover the increasing demand for more affordable disease modifying biologics, and to enable earlier and better access for a large percentage of patients who remain undertreated across many debilitating disease areas while generating savings for healthcare.

Smriti: Shed some light on the study design of the P-III BIIB800 clinical program comparing the safety and immunogenicity of BIIB800 to ACTEMRA.

Dr. Mourad Farouk Rezk: The double-blind 52-week Phase 3 study randomized 621 patients with moderate to severe rheumatoid arthritis in a 2:1:1 ratio to one of three treatment groups: (1) BIIB800 up to Week 48, (2) reference tocilizumab (TCZ) up to Week 48, or (3) TCZ up to Week 24 followed by BIIB800 from Week 24 to Week 48, administered intravenously every 4 weeks at a dose of 8 mg/kg. 

The proportions of subjects with serious treatment-emergent adverse events in Treatment Period 2 were similar between the treatment groups. No deaths were reported during Treatment Period 2. Anti-drug antibody incidence and trough serum concentrations were comparable across the 3 treatment groups.

Smriti: How have data presentations at the European Congress of Rheumatology on June 3, 2022, and the American College of Rheumatology (ACR) on November 10, 2022, contributed to bringing BIIB800 to the attention of patients with rheumatoid arthritis?

Dr. Mourad Farouk Rezk: BIIB800 is a biosimilar candidate referencing ACTEMRA®, an anti-interleukin-6 receptor monoclonal antibody. ACTEMRA is indicated for several indications in the United States, including moderate to severe rheumatoid arthritis in adults as well as juvenile idiopathic polyarthritis and systemic juvenile idiopathic arthritis. Biogen has the responsibility for the development, manufacturing and commercialization of BIIB800 in all countries excluding China (including Hong Kong, Macau and Taiwan). The abbreviated BLA for BIIB800 is under review by FDA and EMA. Biogen has issued a news release about the Phase 3 data presentation of BIIB800 at the European Congress of Rheumatology on June 3, 2022, bringing BIIB800 to the public attention for patients with rheumatoid arthritis.

Smriti: Brief about the commercialization and license agreement between Biogen and Bio-Thera Solutions, Ltd.

Dr. Mourad Farouk Rezk: Biogen announced in April 2021 that it entered into a commercialization and license agreement with Bio-Thera Solutions, Ltd. to develop, manufacture and commercialize BIIB800. Biogen has exclusive regulatory, manufacturing and commercial rights to BIIB800 in all countries excluding China.   

Smriti: Can we talk about the P-I data comparing BIIB800 vs ACTEMRA and other details?

Dr. Mourad Farouk Rezk: The bioequivalence of BIIB800 to its reference products RoActemra/ACEMRA® (marketed in the EU and US, respectively) was demonstrated in a single-dose Phase 1 study when administered at a dose of 4 mg/kg as an intravenous infusion. A comparison of the C_max and AUC values across all three treatment groups indicated that the 90% CIs of the geometric mean for these pharmacokinetic (PK) parameters were within the predefined bioequivalence range of 80–125% for the natural log-transformed data for each comparison. Other PK parameters were also similar across all treatment groups. BIIB800, RoActemra, and ACTEMRA demonstrated similar safety and immunogenicity profiles. Serious adverse events were absent, and all treatment related TEAEs were mild to moderate in severity. Local reactions were also absent. All these factors indicated that the three drugs were well tolerated in this population of healthy volunteers.

Smriti: Lastly, is Biogen planning to release data related to other biosimilar product(s) for any other indication(s)?

Dr. Mourad Farouk Rezk: Biogen has 2 other pipeline assets in biosimilars: SB15 in ophthalmology and BIIB801 in Immunology. Based on the development of their related clinical trials, data would be released at various related congresses based on the indications that are included for selected reviews, formulation presentations, and geographic rights.

Image Source: Canva

About the Author:

Dr. Mourad Farouk Rezk is the Head of Global Medical and Development Biogen Biosimilars. Mourad joined Biogen in 2015 where he was assigned to build and lead Biogen’s Biosimilars medical and regulatory affairs organizations and where he helped establish the scientific milestones of Biogen’s anti-TNFs and anti-VEGFs Biosimilars. Dr. Rezk received his Medical degree with honors from Ais Hams University of Cairo in 1989, after which he specialized in internal medicine and diabetes management and received a master's degree in internal medicine in 1995 as well as a Master of Business Administration in 2000.      

Related Post: Dr. Mourad Farouk Rezk, Head of Global Medical & Development Biogen Biosimilars Shares Insights on Positive P-III Data for BIIB800 (Actemra biosimilar)