The placebo-controlled phase 2 RENEW study (NCT01721161) assessed efficacy and safety of opicinumab (anti-LINGO-1) at 100 mg/kg dosed every 4 weeks for 24 weeks in patients with first-episode acute optic neuritis (AON). Thirty-nine of 82 subjects participated in the multifocal visual evoked potential (mfVEP) sub-study. The pre-specified per-protocol (PP) population showed better recovery with opicinumab versus placebo on VEP latency, which was more pronounced in mfVEP.
The objective of the current study was to assess long-term post-treatment mfVEP outcomes in previous RENEW participants.
RENEWED (NCT02657915) was a 1-day follow-up study 2 years (+up to 12 months) after the last or projected last study visit (Week 32). mfVEP sub-studies were conducted in both RENEW and RENEWED.
Nineteen (48.7%) participants in the RENEW mfVEP sub-study completed RENEWED (opicinumab n=10, placebo n=9). At Day 1 of RENEWED, the difference in latency between affected eye versus baseline of the fellow eye was 8.2±8.5 ms in the opicinumab group and 23.9±16.5 ms in the placebo groups (p=0.01, Student t-test).
Average latency recovery in the affected eye, calculated as difference between latency at RENEW baseline and RENEWED Day 1, was 14.9±11.2 ms (max 35 ms) in the opicinumab group and 6.0±5.8 ms (max 13 ms) in the placebo group (p=0.05). In the opicinumab group, there was a linear relationship between the degree of latency delay at baseline and the latency recovery at RENEWED Day 1 (r2=0.72, p=0.004, Pearson). Conversely, the magnitude of mfVEP latency recovery was limited in the placebo group and did not correlate with initial degree of latency delay (p=0.2), which was consistent with the “natural history” study results of spontaneous optic nerve remyelination following episode of AON1. Finally, between the last visit of RENEW study (24 or 32 weeks) and Day 1 of RENEWED study, mfVEP latency demonstrated a trend for better recovery in the opicinumab group vs placebo group (8.4±7.3 and 2.7±5.6 ms respectively, p=0.07, t-test).
While acknowledging the small sample size of the mfVEP sub-study, the effect of opicinumab on enhanced mfVEP latency recovery was sustained over 2 years ofthe post-treatment period. In addition, a close association between baseline latency delay and degree of latency recovery in opicinumab group suggests that the remyelinating effect of opicinumab treatment may be proportional to the initial degree of demyelination.