Soliris (eculizumab), developed by Alexion Pharmaceuticals, was the first treatment approved by the U.S. Food and Drug Administration in 2019 for adults with neuromyelitis optica spectrum disorder (NMOSD). It is indicated for patients who test positive for aquaporin-4 water channel autoantibodies (AQP4-IgG). It is also approved in the EU, Canada, and Japan.
How does Soliris work?
Many patients with NMOSD have high levels of AQP4-IgG. Antibodies are molecules produced by certain types of immune cells to target foreign invaders such as bacteria and viruses. In autoimmune disorders like NMOSD, some antibodies mistakenly target the body’s own cells. The AQP4-IgG antibodies bind to aquaporin-4 molecules on the surface of astrocytes, a type of glial cell. Glial cells are specialized cells of the nervous system that support nerve cells and form part of the blood-brain barrier, a highly selective, semipermeable membrane.
When AQP4-IgG binds to the surface of astrocytes, it activates the complement pathway of the immune system. This leads to inflammation and the formation of the membrane attack complex (MAC), which is a group of proteins that assemble to form holes in the outer membrane of cells. This causes fluid to rush into the cells, which then causes them to burst. The inflammation and MAC formation are caused by the splitting of a protein in the complement pathway called C5 into C5a and C5b.
Soliris is a humanized monoclonal antibody that inhibits the C5 protein, preventing it from splitting to form C5a and C5b.
Soliris in clinical trials
Soliris was studied in a Phase 1/2 open-label trial (NCT00904826), which enrolled 14 adults with NMOSD. The aim was to establish how effective Soliris was at lowering the rate of NMOSD attacks and improving patients’ outcomes. All participatns received weekly intravenous (IV) infusions of 600 mg of Soliris for four weeks. This was followed by a dose increase to 900 mg at five weeks. After the fifth week, patients started receiving the 900 mg dose every two weeks. Treatment continued for 48 weeks.
Results of the study, published in the journal The Lancet Neurology, showed that 12 of the 14 participants were relapse-free after 12 months of treatment, and none of the participants’ disabilities had worsened. Their median scores on the expanded disability status scale (EDSS) improved from 4.3 to 3.5, wherein higher numbers indicate worse disability. Some patients also improved by one or two points on the Hauser Ambulation Index, a measure of walking ability. In the 12 months after treatment with Soliris ended, eight attacks had occurred in five patients.
A randomized, controlled Phase 3 trial, called PREVENT (NCT01892345), recruited 143 adults with AQ4-IgG-positive NMOSD. The aim was to investigate the safety and efficacy of Soliris compared with a placebo. Researchers randomized participants 2:1 to receive either Soliris or a matching placebo. Patients receiving Soliris received a weekly 900 mg IV infusion for four weeks.
The dose then increased to 1,200 mg in the fifth week. The maintenance phase continued at this dose every two weeks. Patients continued receiving treatment until the end of the trial while investigators recorded the number of relapses. They also assessed any changes patients had in a number of disability metrics, in comparison with the start of treatment.
Researchers had planned the study to end once 24 relapses occurred. However, they decided to end it after 23 relapses as it was unclear how much longer it would be until the 24th incident occurred. Results, published in the New England Journal of Medicine, showed that patients receiving Soliris had a much lower risk of having a relapse than the placebo group. Only three of 96 (3%) patients in the treatment group had a relapse compared with 20 of 47 (43%) in the placebo group.
Patients involved in the PREVENT trial could enroll in an open-label extension trial (NCT02003144) in which they would continue to receive their maintenance treatment for up to four years. This extension trial is intended to evaluate the long-term safety and efficacy of Soliris.
According to a study published in the journal Drugs, combined data from the PREVENT trial and open-label extension showed that Soliris continued to reduce the risk of relapse and lead to improvements in neurological and functional disability assessments even after four years of treatment.
Ongoing clinical trials
Researchers are also investigating Soliris in an open-label Phase 3 trial (NCT04155424) in children, ages 2 to 17, with AQ4-IgG-positive NMOSD. The study is currently recruiting up to 15 participants at locations in the U.S., Japan, and Spain, with a location in South Korea opening soon.
Participants will receive doses according to their body weight and in a similar pattern to adults. An induction phase in which they receive weekly doses will precede a maintenance phase in which they will receive treatments every two weeks. Patients will receive treatment for 52 or 53 weeks. They then will have the option of continuing treatment during an extension period of 104 weeks.
The annualized relapse rate (number of relapses per year) and time to first relapse will be compared between week 52 or 53 and the start of the study. Researchers will also monitor changes in several disability metrics and blood test levels of Soliris and the C5 protein throughout the study. They expect to conclude the study in December 2024.
Soliris infusions can potentially lead to life-threatening meningococcal infections.
Common side effects of Soliris in NMOSD patients include upper respiratory infections, pain or swelling in the throat or nose, diarrhea, back pain, dizziness, fever, headache, tiredness, cough, sore throat, joint pain, and bruising.
Soliris is also approved for the treatment of atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, and generalized myasthenia gravis.
Last updated: Dec. 4, 2020
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