WASHINGTON -- Researchers here say they have the first biological proof of remyelination, with positive results from a phase II study showing that a novel monoclonal antibody improved nerve signaling in acute optic neuritis.
Biogen's anti-LINGO-1 monoclonal antibody (BIIB033) significantly improved recovery of optic nerve latency -- the time it takes for a signal to travel from the retina to the brain's visual cortex -- compared with placebo in a per-protocol analysis, with a difference of 9.13 msec (P=0.01), according to , of Biogen.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
But there were no differences in retinal thickness or visual function, Cadavid reported during an emerging science session at the American Academy of Neurology meeting here.
"This is the first evidence of remyelination in the clinic," Cadavid said during the presentation.
The enrolled 82 patients who'd had a first episode of unilateral acute optic neuritis. Patients were randomized to either 100 mg/kg of the drug or placebo, given once every 4 weeks for a total of six doses, and were followed for 32 weeks.
Remyelination was assessed via recovery of optic nerve conduction latency, which was measured by full-field visual evoked potential (FF-VEP). They also assessed neuroprotection via retinal thickness on spectral-domain optical coherence tomography (SD-OCT), as well as eye function on low-contrast letter acuity (LCLA).
In the per-protocol analysis, the researchers found that drug-treated patients had a significantly greater improvement in latency recovery than those on placebo, with a difference of 7.55 msec at 24 weeks (P=0.05) and a difference of 9.13 msec (P=0.01) at 32 weeks.
Those differences, however, were not significant in the intention-to-treat population.
Nor were there any differences in the secondary endpoints of change in thickness of the retinal layers, or in visual function.
"Data indicate that significant retinal layer thinning had taken place before the first treatment was administered -- half prior to the first dose, remainder prior to second dose -- indicating that anti-LINGO-1 may not have had an opportunity to impact neuroprotection," Cadavid said in an email to ľֱ.
The drug was generally well-tolerated, Cadavid said, noting that the most common adverse events with the drug were fatigue, nausea, and paresthesia.
Two drug-treated patients had hypersensitivity reactions that occurred around the time of infusion, and one patient had an asymptomatic elevation in liver transaminases.
Cadavid concluded that the improved conduction of electrical impulses along the optic nerve seen in the trial provides the first evidence that remyelination is biologically possible.
, of the Mayo Clinic in Arizona, who was not involved in the study, said the "prospect of having a truly neuroprotective or remyelinating therapy is very exciting and this early-phase protocol begins to address the unmet need of limiting the degree of lasting neurological injury that results from acute MS attacks."
While the preliminary data are promising in terms of both safety and efficacy, Wingerchuk was cautious about its lack of effect on "clinically important visual outcome measures" -- suggesting that a "much greater understanding of the mechanisms and durability of the detected changes are needed."
"Despite these and other limitations," Wingerchuk added, "the data provide support for further research and cautious optimism."
Disclosures
The study was supported by Biogen.
Cadavid is an employee of Biogen.
Primary Source
American Academy of Neurology
Source Reference: Cadavid D, et al "Evidence of remyelination with the anti-LINGO-1 monoclonal antibody BIIB033 after acute optic neuritis" AAN 2015; Abstract ES-008.