Promising step in rheumatoid arthritis: BI-695501 demonstrated clinical equivalence to Adalimumab
Boehringer Ingelheim recently (Annual European Congress of Rheumatology, EULAR-17) announced the results from the pivotal Phase III VOLTAIRE-RA study, confirming that its adalimumab biosimilar candidate BI-695501 have similar efficacy, safety and immunogenicity in moderately-to-severely active rheumatoid arthritis patients. VOLTAIRE is a multinational, multicentre, randomised, double-blind, parallel arm study. Approximately, 645 patients (18–80 years) with moderate to severe rheumatoid arthritis active on stable treatment with methotrexate were randomised to receive adalimumab or BI-695501 (40 mg for 24 weeks). At week 24, patients on adalimumab were re-randomised to continue the adalimumab originator or switch to BI-695501 until week 48. The co-primary endpoints of ACR20 response at weeks 12 and 24 were within the pre-defined criteria for equivalence, demonstrating clinical equivalence between BI-695501 and the adalimumab. No deaths were reported during the study. Similar frequencies of patients tested positive for anti-drug antibodies (BI-695501 43.2%; adalimumab 47.8%), and neutralising antibodies (BI-695501 16.0%; adalimumab 20.6%) in both groups at Week 24. Results demonstrated that BI-695501 and the adalimumab are highly similar in terms of efficacy, safety and immunogenicity and confirm the clinical efficacy equivalence of BI 695501 to adalimumab.
Pre-filled Syringe vs Autoinjector:
Boehringer Ingelheim also presented data from the VOLTAIRE-AI study at EULAR 2017, demonstrating pharmacokinetic similarity of BI-695501’s pre-filled syringe (PFS) and auto-injector (AI). VOLTAIRE-AI study is a randomised, single-dose, open-label, parallel-group study, 40 mg BI-695501 was administered either via pre-filled syringe or autoinjector in healthy, male, volunteers aged 18–65 years with body mass index (≥18 to ≤30). Seventy-one volunteers were randomised: PFS=36; AI=35. Estimates for AI/PFS geometric mean (gMean) ratios were within the standard bioequivalence acceptance range (80–125%) and mean plasma concentration-time profiles and total exposure for BI-695501 administered via PFS or AI were found to be similar over the observation period. PK, safety, tolerability, and immunogenicity of BI-695501 after SC injection with a PFS or an AI were found comparable.
There are also multiple other players, who are developing biosimilars of adalimumab. Amgen’s Humira biosimilar Amjevita is leading the space as it is already approved in the US in 2016 and in 2017 by EC. Coherus Biosciences, Momenta Pharmaceuticals and Sandoz have also reported positive phase III data and are in the race for the approval. HUMIRA is an approved biologic medicine for the treatment of multiple chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Boehringer Ingelheim’s BI-695501 is currently under review by both the EMA and FDA. With the positive phase III results, BI-695501 would be in the strong line of approval, and if approved, it would give high quality and cost effective treatment options to RA patients.
By Dr. Rupesh Tyagi
Senior Research Analyst, Science and Research @ Innoplexus