Other names: BIIB033
Opicinumab is a new drug treatment being evaluated for promotion of remyelination of nerve cells. It is taken as an intravenous infusion (drip) every four weeks.
Opicinumab for remyelination of nerve cells: Phase II
- Opicinumab is thought to promote the development of oligodendrocytes, the cells which maintain myelin coating around nerves.
- In a phase II study of people diagnosed with optic neuritis, opicinumab treatment resulted in a small but significant improvement in transmission of nerve impulses in the optic nerve. In a second phase II study of people with relapsing remitting and secondary progressive MS, opicinumab failed to show an improvement or a slowdown of disability progression.
- No significant side effects have been seen in early clinical studies.
How does opicinumab work?
Myelin is a fatty protein that forms a sheath around the axons of nerve cells - the part of the cell that transmits messages to other nerve cells. Myelin acts as insulation to the axon and helps maintain the speed of transmission of messages. In the central nervous system, myelin is produced by cells called oligodendrocytes.
Damage to myelin (or demyelination) caused by multiple sclerosis interrupts or blocks nerve messages. In the earlier stages of MS, oligodendrocytes can often repair areas of damaged myelin - a process known as remyelination. As MS becomes more established, these cells stop functioning or are killed off and myelin is not repaired, resulting in increasing disability.
A protein called LINGO-1 which occurs only in the central nervous system prevents the development of young cells into oligodendrocytes. Opicinumab (also known as anti-LINGO-1) has been found to block the action of LINGO-1, allowing young cells to mature into oligodendrocytes. This may restore repair of damaged myelin, offering the potential for preventing or possibly reversing disability.
How is opicinumab taken?
In early clinical trials, opicinumab has been taken as an intravenous infusion every four weeks.
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.
In the phase II SYNERGY study, no significant side effects were reported.
- Neurology: Neuroimmunology & Neuroinflammation 2014;1(2):e18. Full article Randomised phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033.
- Lancet Neurology 2019; 18: 845-856 Summary Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial
- Neurology 2019; 92 (15 Supplement), P3.2-072 Full article Phase 2 AFFINITY Trial Evaluates Opicinumab in a Targeted Population of Patients With Relapsing Multiple Sclerosis: Rationale, Design and Baseline Characteristics (P3.2-072)
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