Shots :

• Dr. Mourad talked about the positive P-III data showing results for BIIB800, a Tocilizumab biosimilar candidate presented at the Annual European Congress of Rheumatology (EULAR 2022)
• He also spoke about the results of the 48-week analysis of the PROPER trial evaluating   adalimumab biosimilar, Imraldi, in patients with autoimmune diseases
• The interview highlights Biogen's advancements in addressing challenging immunologic conditions that could help patients to tackle these complex diseases

Smriti: Thanks for taking out time to talk to us. How was the ACR’22 experience for biosimilars for Biogen? We saw Biogen presented multiple results for different biosimilar molecules. So how was your overall response?

Dr. Mourad Farouk Rezk: At the Annual Meeting of the American College of Rheumatology (ACR 2022), Biogen presented Phase 3 data for BIIB800, a candidate biosimilar to tocilizumab, and the 48-week analysis of “PROPER," a pan-European real-world study of the adalimumab biosimilar IMRALDI^TM following transition from reference adalimumab in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), and the overall response was resoundingly positive.

Smriti: Can we talk about BIIB800, a tocilizumab biosimilar? Can you please talk about the trial and the results which were presented at ACR’22?

Dr. Mourad Farouk Rezk: The 52-week results from the Phase 3 study for BIIB800, a biosimilar candidate referencing ACTEMRA®/RoActemra® (tocilizumab), an anti-interleukin-6 receptor monoclonal antibody, were presented at ACR’22.

The results of this Phase 3 randomized, double-blind, active-controlled comparative clinical trial showed that efficacy, pharmacokinetic (PK), safety and immunogenicity of BIIB800 and reference tocilizumab remained comparable through 52 weeks and that no safety or clinically relevant immunogenicity differences were observed in subjects who switched from reference tocilizumab to BIIB800.

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 trial met its primary endpoints of ACR20* response at Week 12 and Week 24. The results up to Week 24 (Treatment Period 1) were previously reported at the EULAR European Congress of Rheumatology in 2022.

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 (Treatment Period 2) were reported at this year’s 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 three treatment groups. 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: We see the BIIB800 is in Ph3, what is the timeline Biogen has in mind for filling and launch, and in which indications?

Dr. Mourad Farouk Rezk: The European Medicines Agency (EMA) and the U.S Food and Drug Administration (FDA) have accepted the Marketing Authorization Application and the abbreviated Biologics License Application (aBLA), respectively, for BIIB800 in Q4 2022 with the Phase 3 trial being conducted in rheumatoid arthritis (RA) patients. Both dossiers are under review, and it would not be appropriate to speculate on approval or launch timelines.

Smriti: Does Biogen plan to assess BIIB800 in other indications beyond RA? What is the expected timeline for the same?

Dr. Mourad Farouk Rezk: In the U.S., ACTEMRA® is indicated for several indications in addition to RA. These include juvenile idiopathic polyarthritis and systemic juvenile idiopathic arthritis. At this point, we are not able to speculate on any additional indications for BIIB800 or potential timelines.

Smriti: Can we talk about IMRALDI’s (adalimumab biosimilar) PROPER study and its design?

Dr. Mourad Farouk Rezk: The “PROPER” study is a pan-European real-world non-interventional study of patients with immune-mediated inflammatory disease. 1,040 patients with rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, ulcerative colitis or Crohn's disease were enrolled under an umbrella design. Patients have switched after at least 16 weeks’ treatment with reference adalimumab to biosimilar adalimumab (IMRALDI^TM) as part of routine clinical practice and are followed for 48 weeks after switch.

Smriti: Please talk about the results of the PROPER trial Biogen presented at ACR’22 in detail.

Dr. Mourad Farouk Rezk: The results presented at ACR were for the RA, axSpA and PsA cohorts aiming to evaluate candidate predictors of persistence (time to discontinuation up to Week 48 post-transition) on IMRALDI^TM.

The study showed that treatment effectiveness and IMRALDI dose regimen were maintained at 48 weeks after switching from reference product. Probability of persistence at Week 48 was 85.9%, 79.5% and 81.1% for RA, axSpA, and PsA, respectively. Among the candidate predictors of persistence, only female gender was found to have a significant association with increased risk for discontinuation in study subjects diagnosed with RA or axSpA. This additional analysis from a large, contemporary cohort of patients with established disease provides patients and prescribers with further evidence and reassurance that switching from reference adalimumab to IMRALDI is safe and effective, with high persistence throughout the cohort.

Smriti: Can Biogen share any RWE (Real World Evidence) analysis which shows switching results from Humira to IMRALDI?

Dr. Mourad Farouk Rezk: There is a growing body of evidence from routine clinical practice on transition from reference to biosimilar biologics. PERFUSE is an ongoing non-interventional study including 916 patients diagnosed with rheumatological or gastroenterological inflammatory diseases (509 rheumatology patients and 407 gastroenterology patients) receiving IMRALDI^TM as routine therapy. PEFRUSE aims to evaluate the effectiveness and safety of IMRALDI as well as patient satisfaction in naïve and switched patients. 188 (37.1%) and 156 (38.3%) of switched patients were included in the rheumatology and gastroenterology cohort respectively. 

Smriti: What were the other results from biosimilars presented during ACR’22?

Dr. Mourad Farouk Rezk: A considerable number of biosimilar results on various topics were presented. Phase 1 and Phase 3 study data demonstrated bioequivalence and equivalent efficacy, and comparable safety and immunogenicity profiles, and interchangeability of biosimilar candidates to the reference products, respectively. Multiple sessions and presentations focused on real-world data on the transition, including multiple switches, from originator products to biosimilars, whereas others covered health economic analyses of the use of biosimilars.

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.      

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