Safety and Efficacy of Opicinumab in Acute Optic Neuritis (RENEW Trial)
The human monoclonal antibody opicinumab (also known as BIIB033 and anti-LINGO-1) has shown remyelinating activity in preclinical studies. As a result, Cadavid et al. assessed the safety, tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode. They found no significant difference in remyelination between the opicinumab and placebo groups in the intent-to-treat (ITT) population at week 24.
This randomized double-blind placebo-controlled phase 2 study (RENEW) included 82 patients (aged 18-55) who had a first unilateral acute optic neuritis episode within 28 days from baseline (ITT group). After being treated with high-dose methylprednisolone for 3-5 days, they were randomized 1:1 to receive either 100 mg/kg of opicinumab intravenously or placebo every 4 weeks (6 doses) and followed until week 32. In a subset of the ITT group, 69 patients completed the study per protocol (PP): 33 in the opicinumab group and 36 in the placebo group. The primary study endpoint was remyelination at 24 weeks, measured as recovery of affected optic nerve conduction latency using full-field visual evoked potential (FF-VEP) versus the unaffected fellow eye at baseline. Separate prespecified analyses were completed for the ITT and PP groups.
The researchers found an adjusted mean treatment difference in optic nerve conduction speed between the opicinumab and placebo groups of −3.5 ms in the ITT population (p = .33) and −7.6 ms in the PP population (p = .05) at week 24; and −6.1 ms in the ITT population (p = .07) and −9.1 ms in the PP population (p = .11) at week 32. The overall incidence and severity of adverse effects were similar between the active drug and placebo groups, and no significant effects on brain MRI measures were noted in either group.
However, the researchers noted that there was a significant difference between active drug and placebo in the PP population at week 32. They concluded that these findings suggest that enhanced remyelination with opicinumab might be possible; and, thus, further clinical investigations are warranted.
The original article can be found here.