Date: 2016-06-07
Type of information: Results
phase: 2
Announcement: results
Company: Biogen (USA - MA)
Product: opicinumab (anti-LINGO-1 - BIIB033)
Action
mechanism: monoclonal antibody. Opicinumab is an anti-LINGO-1 (leucine-rich repeat and Ig-containing Nogo receptor interacting protein-1) monoclonal antibody. LINGO-1 is a membrane protein selectively expressed in the CNS. It prevents the development of young cells into oligodendrocytes and suppresses myelination, preventing the repair of damaged axons. Opicinumab could block these processes and allow for the re-myelination and restoration of nerve communication in multiple sclerosis patients.
Disease: relapsing multiple sclerosis
Therapeutic area: Neurodegenerative diseases
Country:
Trial
details: The two Phase 2 trials (RENEW and SYNERGY) were designed to assess the biological activity and clinical potential of opicinumab (anti-LINGO-1) in central nervous system (CNS) demyelinating diseases.RENEW was a randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the effect of opicinumab treatment following a first episode of acute optic neuritis. Opicinumab 100 mg/kg was administered intravenously once every four weeks for 20 weeks (total of six doses). Results from RENEW showed improved latency recovery, as measured by the primary endpoint full-field visual evoked potential (FF-VEP), among opicinumab participants, compared with placebo. The study showed no effect on the secondary endpoints of change in thickness of the retinal layers (optic nerve neurons and axons) or visual function, as measured by spectral domain optical coherence tomography (SD-OCT) and low contrast letter acuity, respectively. SYNERGY was a randomized, double-blind, placebo-controlled, dose-ranging Phase 2 study that evaluated the impact of opicinumab among 418 participants with relapsing forms of multiple sclerosis (both relapsing-remitting and secondary progressive) over 72 weeks. The primary endpoint of the SYNERGY study was a multicomponent measure evaluating the number of study participants who experienced three month confirmed improvement of ambulation (Timed 25-Foot Walk; T25FW), upper extremity function (9-Hole Peg Test; 9HPT), cognition (3-Second Paced Auditory Serial Addition Test; PASAT) and standard measures of physical disability (Expanded Disability Status Scale; EDSS). Secondary endpoints measured slowing of progression on the same components, as well as the safety and pharmacokinetics of opicinumab. Statistical testing assessed the dose-response trend based on the primary or secondary endpoint. Opicinumab was administered intravenously every four weeks at doses of 3 mg/kg, 10 mg/kg, 30 mg/kg or 100 mg/kg. All study participants received concurrent treatment with 30 mcg interferon beta-1a intramuscular injection once weekly.
Latest
news: * On June 7, 2016, Biogen reported top-line results from the Phase 2 SYNERGY study evaluating opicinumab (anti-LINGO-1), an investigational, fully human monoclonal antibody being developed as a potential neuroreparative therapy in people with relapsing forms of multiple sclerosis (RMS). In the study, opicinumab missed the primary endpoint, a multicomponent measure evaluating improvement of physical function, cognitive function, and disability. However, evidence of a clinical effect with a complex, unexpected dose-response was observed. Opicinumab also did not meet the secondary efficacy endpoint in SYNERGY, which evaluated the slowing of disability progression. Safety and pharmacokinetics (PK) were also assessed as secondary endpoints. Opicinumab was generally well-tolerated and the safety profile was consistent with what has been observed in prior studies. Opicinumab showed a linear, well-behaved PK profile over the studied dose range. SYNERGY results will be presented at future medical meetings.
