The FINANCIAL — On April 14, Biogen announced detailed results from the Phase 2 RENEW study of anti-LINGO-1 in acute optic neuritis (AON) – the first clinical study to demonstrate remyelination (the formation of new myelin on axons) following an inflammatory injury in humans.
These data will be presented at the 67th Annual Meeting of the American Academy of Neurology (AAN) in Washington, DC, next week, according to Biogen.
The new data demonstrate a statistically significant improvement in recovery of optic nerve conduction latency (time for a signal to travel from the retina to the brain’s visual cortex), as measured by the primary endpoint full-field visual evoked potential (FF-VEP), among anti-LINGO-1-treated participants at the last study visit (week 32), as compared to placebo. Results from a sub study of multifocal VEP (mfVEP) are consistent with the FF-VEP findings. These data supplement the top-line, 24-week RENEW results reported by Biogen in January 2015.
“RENEW is the first study to show repair of the human central nervous system (CNS) through remyelination, and the results support our ongoing development of this molecule,” said Alfred Sandrock, M.D., Ph.D., group senior vice president and chief medical officer at Biogen. “We believe the anti-LINGO-1 data point toward a potential new approach to treating demyelinating diseases, and we look forward to the ongoing Phase 2 SYNERGY study results to further clarify the potential of this investigational therapy in MS.”
RENEW Results in AON
Primary endpoint: FF-VEP
Results from RENEW show improved latency recovery, as measured by the primary endpoint, FF-VEP, among anti-LINGO-1 participants, compared with placebo. Per-protocol participants (those who were treated with at least five of the six doses of anti-LINGO-1) showed a 34 percent improvement of 7.55 milliseconds in optic nerve conduction latency at week 24, compared with placebo (p=0.05). Further latency recovery was observed at the last study visit (week 32), with a statistically significant 41 percent improvement of 9.13 milliseconds, compared with placebo (p=0.01). Together, the data demonstrate evidence of treatment effect with continuous improvement observed 12 weeks following the last study dose (week 20).
In a pre-specified analysis, 53 percent of anti-LINGO-1 participants demonstrated normal or nearly normal (within 10 percent of the normal, unaffected eye) FF-VEP latency, compared with 26 percent of participants in the placebo group.
Additional endpoints
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. The retinal ganglion cell layer analysis demonstrated that considerable thinning had taken place before treatment was administered. As a result, anti-LINGO-1 may not have had an opportunity to provide evidence of neuroprotection in this study.
“RENEW studied two distinct mechanisms of action – remyelination and neuroprotection,” said Dr. Sandrock. “We believe that the opportunity to impact neuroprotection was limited by the rapidity with which retinal ganglion cells and their nerve fibers were damaged by the disease. This insight offers valuable information on the speed of axonal loss following an AON attack, and combined with the positive primary endpoint results, will help inform future studies.”
The FF-VEP RENEW findings were consistent with results from a sub study of 39 participants using mfVEP, a novel, more sensitive method of measuring latency recovery and amplitude changes following AON.
Safety & tolerability
Anti-LINGO-1 was generally well tolerated. The overall incidence and severity of adverse events (AEs) was comparable across treatment arms. The most common AEs occurring at higher rates in the anti-LINGO-1 arm than the placebo arm were fatigue, nausea and paresthesia. Treatment related anti-LINGO-1 serious adverse events (SAEs) consisted of two participants with hypersensitivity reactions occurring around the time of infusion and one participant with an asymptomatic elevation in liver transaminases, all of which resolved after drug discontinuation. No deaths occurred during the trial. No immunogenicity was observed.
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