Orelabrutinib has the potential to inhibit B cell and myeloid cell effector functions in the central nervous system and may provide a clinically meaningful benefit on progression in all forms of MS.
According to a recent announcement, Biogen and InnoCare Pharma have entered into a license and collaboration agreement for orelabrutinib, an oral small molecule Bruton’s tyrosine kinase inhibitor (BTKi) for the treatment of multiple sclerosis (MS). The drug is currently being investigated in a global phase 2 study (NCT04711148) in patients with relapsing-remitting MS (RRMS).
InnoCare will receive $125 million upfront payment and is eligible to receive up to $812.5 million in potential development milestones and potential commercial payments should the drug reach specific development and commercial milestones, and sales thresholds. In addition, the company will also maintain orelabrutinib’s exclusive worldwide rights in the field of cancer. The agent has received prior approval from the China National Medical Products Administration to treat both patients with relapsed/refractor chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as patients with relapsed/refractory mantle cell lymphoma.
Orelabrutinib, a covalent BTKi with high selectivity, can cross the blood brain barrier, thus inhibiting B cell and myeloid cell effector functions in the central nervous system (CNS). By addressing the progressive biology of the disease, the companies believe orelabrutinib has the potential to slow disease progression and provide clinically meaningful benefit in all forms of MS.
"Given the complex and chronic nature of MS, we believe the unique characteristics of orelabrutinib, combining high selectivity and CNS penetrance, may translate to potential clinical advantages relative to other BTKi programs,” Alfred Sandrock Jr, MD, PhD, Head, Research and Development, Biogen, said in a statement. “For over 30 years, Biogen has led in MS research and today has a leading portfolio of MS products. We are focused on developing next-generation approaches that we hope will improve outcomes for those living with progressive and relapsing forms of MS.”
In November 2020, the FDA cleared an investigational new drug (IND) application for the phase 2, randomized, double-blind, placebo-controlled, multicenter study of orelabrutinib, which was expected to enroll 160 patients with RRMS. Investigators will evaluate the agent on the cumulative number of new gadolinium-enhancing T1 MRI brain lesions over 12 weeks of treatment. Other secondary outcome measures include incidence of treatment-emergent adverse events, annualized relapse rate, and dose escalation peak concentration.
"Biogen is a recognized leader in neuroscience and we believe this transition will help advance the development of orelabrutinib in MS,” Jasmine Cui, PhD, co-founder, chairwoman, and chief executive officer, InnoCare, said in a statement. “We are excited about the potential of orelabrutinib for the treatment of patients with all forms of MS given the potential efficacy and safety profile, plus a promising level of blood-brain barrier penetration. BTK inhibitors may have the potential to transform the treatment paradigm of autoimmune diseases, in particular MS.”
Other BTK inhibitors, such as Sanofi’s tolebrutinib (previously known as SAR442168), Roche’s fenebrutinib, and EMD Serono’s evobrutinib, are currently being evaluated as potential MS therapies in phase 3 trials. Thought leaders Lawrence Steinman, MD, and Enrique Alvarez, MD, PhD, recently sat down for a NeurologyLive Insights series to discuss the role of BTK inhibitors and review the potential impact on patients with progressive MS. Watch below as they give their thoughts.