Anti-LINGO-1 / BIIB033 / Opicinumab for RRMS

Opicinumab (also known as anti-LINGO-1 and BIIB033) is an investigational monoclonal antibody being developed by Biogen to promote the remyelination of nerve cells in people with remitting-relapsing multiple sclerosis (RRMS).

How opicinumab works

MS is characterized by demyelination, or loss of the myelin sheath, a protective layer that surrounds the nerve fibers. This interrupts and blocks the passage of electrical signals through the nerve cells. In earlier stages of MS, oligodendrocytes (cells that make and maintain the myelin coating) can repair the damaged myelin, but as the disease progresses, oligodendrocytes either stop functioning or die, and they stop repairing myelin.

The brain and the spinal cord have a unique protein called LINGO-1 that prevents immature cells from becoming oligodendrocytes. Opicinumab is an antibody (a protein designed to target and bind to a specific protein), which blocks the action of LINGO-1 (hence the name, anti-LINGO-1), allowing these cells to mature into oligodendrocytes. These new oligodendrocytes may help restore the damaged myelin and prevent permanent nerve damage, which causes further disability in patients.

Opicinumab in clinical trials

A Phase 2 study called RENEW (NCT01721161), assessed the effectiveness, safety, and tolerability of opicinumab in 82 people with acute optic neuritis, a condition highly associated with MS and characterized by the inflammation and demyelination of the optic nerve — the bundle of nerves that transmits visual information from the eye to the brain.

Although the results of the study showed no improvements in vision in people taking opicinumab compared to those taking a placebo, there was a slight improvement and statistically significant change in the amount of time it took for a signal to travel from the eye to the brain. This finding suggested repairs to the myelin sheath around the optic nerve. The results were published in the scientific journal Lancet Neurology.

A follow-up study called RENEWed (NCT02657915) assessed the long-term effects of a potential remyelinating therapy in participants who took part in the RENEW trial, two years and four months after that trial was concluded. RENEWed, which ended in January 2017, assessed eye evoked potential latency (or the delay in electric signals in response to a light stimulus), as well as the clinical progression and severity of demyelination in patients. Results have not yet been published.

Another Phase 2 study called SYNERGY (NCT01864148) assessed the effectiveness, safety, tolerability, and pharmacokinetics of opicinumab in 418 RRMS patients being treated concurrently with Avonex (interferon beta-1a). Patients received either 3 mg, 10 mg, 30 mg, or 100 mg/kg body weight of opicinumab every four weeks for a period of 72 weeks.

Initial results from Biogen suggested that opicinumab did not improve physical or cognitive disability, lead to a slowdown in the progression of disability. However, patients treated with intermediate doses of opicinumab (10 and 30mg/kg) showed a 65.6 percent and 68.8 percent improvement in Expanded Disability Status Scale (EDSS) scores, compared to an improvement of 51.6 percent in the placebo group. These results were presented at the 2017 American Academy of Neurology (AAN) Annual Meeting. 

No serious adverse effects of the treatment were reported in any of the studies.

Biogen intends to continue trials with opicinumab, potentially in conjunction with anti-inflammatory drugs such as Tysabri (natalizumab).

Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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