A phase II study of the “anti-LINGO-1” repair strategy in people with optic neuritis, which is often the first clinical episode of multiple sclerosis, met its primary endpoint, announced Biogen Idec in a press release on January 8. Treatment improved nerve impulse conduction in the eyes in a study of 82 people who had experienced a first episode of this inflammation of the optic nerve, although it is not yet clear if this improvement reflects repair of damage. The trial was sponsored by Biogen Idec. Also ongoing is a study of this compound in 419 people with relapsing forms of MS.
Phase II studies such as this one are designed to provide indicators of safety, benefits and optimal dosing, but larger, longer phase III studies are required to support applications for marketing approval from drug regulatory agencies such as the U.S. Food and Drug Administration.
Background: In MS, immune attacks lead to the loss of myelin that coats and protects nerve fibers in the brain and spinal cord. Repairing the nervous system was just a dream a few years ago. Today it holds significant promise as a strategy to restore the function that MS has taken from people; and reducing or stopping MS progression. This remarkable progress is due in large part to the National MS Society’s comprehensive efforts and multi-million dollar research investments. Today the Society is supporting 87 research projects in nervous system repair, with multi-year commitments totaling over $35 million.
The human trials of anti-LINGO leverage research aimed at stimulating the body’s natural healing abilities. LINGO is a protein seen in nerve cells and cells that make nerve-insulating myelin (oligodendrocytes). Blockading this protein with a monoclonal antibody called anti-LINGO has been shown to promote myelin repair in animal models. In two phase I human safety trials in people with relapsing-remitting or secondary-progressive MS, no serious adverse safety events were reported.
Assessing visual outcomes in acute optic neuritis – inflammation of the optic nerve that often presents as the first clinical episode of MS – shows promise as a possible model for screening compounds for their ability to protect the nervous system and repair myelin. The optic nerve is one of the few locations in the central nervous system that can be assessed directly and noninvasively.
The Study: For this phase II study, investigators recruited 82 people who had experienced a first episode of acute optic neuritis at 33 sites in Europe, Canada, and Australia for this trial, called the RENEW trial. Participants received intravenous infusions of 100 mg/kg anti-LINGO-1 or inactive placebo every four weeks for 24 weeks.
The primary endpoint of the study was whether treatments improved optic nerve impulse conduction, as measured by visual evoked potential tests. Evoked potential tests measure the electrical activity of the brain in response to stimulation of specific sensory nerve pathways. They are able to detect the slowing of electrical conduction that may be caused by myelin damage along these pathways even when the change is too subtle to be noticed by the person or to show up on neurologic examination.
Preliminary results reported in the press release suggest that 34% of the participants who completed the study showed improvement in optic nerve impulse conduction in the anti-LINGO-1 group, compared to on placebo, although it is not yet clear if this improvement reflects repair of damage.. No effect was shown on secondary endpoints, including change in thickness of the optic nerve fiber layers and visual function.
Three serious adverse events were reported in those onanti-LINGO-1 and not in those on placebo, including two patients with hypersensitivity reactions occurring around the time of infusion and one elevation in liver enzymes, which resolved after treatment was discontinued. Otherwise the treatment was well tolerated.
Comment: Analysis of this study is ongoing and full results will be presented at a medical meeting later this year, according to the press release. The SYNERGY study, which is assessing the safety and effectiveness of anti-LINGO-1 in 419 people with relapsing forms of MS, is ongoing and has completed enrollment. Full results from these studies will help to determine if anti-LINGO-1 can repair damage and restore function in people with MS.
Read more about research to repair the nervous system in MS.