Opicinumab was an experimental drug investigated as a treatment to promote myelin repair in multiple sclerosis.
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.
Opicinumab is taken as an intravenous infusion (iv drip) every four weeks.
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.
This phase II clinical trial was designed to detect whether treatment with opicinumab would result in remyelination. 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.
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.
This phase II study was 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 took either opicinumab or placebo for 72 weeks, in addition to a disease modifying drug (Avonex, Plegridy, Betaferon, Rebif, Tecfidera or Tysabri). Disability was 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. In October 2020, Biogen announced that the study did not meet its primary or secondary endpoints and that they had discontinued development of opicinumab.
There are no plans to carry out further clinical trials of opicinumab.
In the phase II SYNERGY study, no significant side effects were reported.
