Opicinumab (anti-LINGO-1)

What are the results so far?

In a phase I study, the safety and tolerability of different doses of opicinumab were evaluated in healthy volunteers and participants with relapsing remitting and secondary progressive MS and compared with placebo. No serious side effects were seen and there was no difference in the frequency of milder side effects (such as headache or chest infection) between opicinumab or placebo.

• RENEW - opicinumab in acute optic neuritis

Preliminary results of the RENEW study have been presented at a scientific meeting. The trial was designed to detect whether treatment with opicinumab would result in remyelination.

In this phase II clinical trial opicinumab was tested against placebo in 82 people who'd recently had a first episode of optic neuritis (but did not have MS). Participants received a total of six intravenous infusions of the drug or placebo every four weeks and were followed up for a total of 32 weeks. Opicinumab was no better than placebo at improving vision, but researchers found that the time for a signal to travel from the retina of the eye to the brain (measured by visual evoked potentials) was improved slightly but statistically significantly in those who took opicinumab, providing possible evidence that the myelin sheath around the optic nerve had indeed been repaired.

One observer at the meeting noted that the dose of opicinumab was very high and might lead to significant side effects when taken long term, so this will need to be monitored in further clinical trials.

• SYNERGY - opicinumab in combination with Avonex

This phase II study was designed to detect whether treatment with opicinumab could improve disability.  418 participants with relapsing remitting or secondary progressive MS took Avonex (interferon beta 1a) once a week in combination with different doses of opicinumab or placebo by intravenous infusion every 4 weeks, for 72 weeks. Disability was monitored using a combination of measures of walking ability, arm and hand dexterity, cognition and EDSS. Opicinumab treatment did not lead to an improvement in disability or a slowdown in disability progression. However, there were indications of a clinical effect. More detailed analysis of the data identified an effective dose and subgroup (based on MRI measures and disease duration) which may have an enhanced response to opicinumab.

What further research is planned?

• AFFINITY - opicinumab in combination with disease modifying drugs

This phase II study is similar to SYNERGY but with more specific criteria (based on detailed MRI assessment) designed to select the subgroup most likely to respond to opicinumab. 263 participants with relapsing remitting MS will take either opicinumab or placebo for 72 weeks, in addition to a disease modifying drug (Avonex, Plegridy, Betaferon, Rebif, Tecfidera or Tysabri). Disability will be monitored using a combination of measures: EDSS, walking ability (time to walk 25 feet), cognition (paced auditory serial addition test) and manual dexterity (nine hole peg test) in both the dominant and non-dominant hand. Side effects of treatments will also be monitored.

Estimated completion date May 2022.
Further details of this study.