Soliris (eculizumab), developed by Alexion Pharmaceuticals, is approved by the U.S. Food and Drug Administration (FDA) and the European Commission to treat certain adults with generalized myasthenia gravis. It is given as an intravenous (IV) infusion once a week for one month, followed by a fifth dose one week later and then ongoing infusions once every two weeks.
How Soliris works
Myasthenia gravis is an autoimmune neuromuscular disease in which a person’s immune system attacks the nervous system, affecting the transmission of messages — nerve impulses — to muscle cells. This leads to overall weakness and lack of muscular control, including over muscles essential to chewing and swallowing, talking and breathing.
Normally, to pass on a message to a muscle, motor neurons release a chemical called acetylcholine at the neuromuscular junction — the point where the nerve and muscle cells interact.
Acetylcholine binds to acetylcholine receptors (AChRs) found on muscle cells, causing muscles to contract. In many myasthenia gravis patients, the immune system starts to produce antibodies — a type of immune protein that interacts with a specific target — that prevent AChRs from working and can destroy them.
Soliris is designed to block part of the immune system called the terminal complement cascade, consisting of a series of reactions that trigger the damaging immune response seen in myasthenia gravis. Soliris binds to and inhibits the cleavage of a protein called C5, an essential step at the start of the cascade.
Soliris in clinical trials
The European Commission approved Soliris as the first treatment for generalized myasthenia gravis in August 2017, followed by the FDA in October of that year, Alexion announced in a press release. It is approved for adult generalized myasthenia gravis patients who are anti-acetylcholine receptor (AchR) antibody-positive.
FDA approval followed demonstrated benefits for these patients in a Phase 3 clinical trial (NCT01997229) called REGAIN.
The trial, which ended in June 2016, was a double-blind, placebo-controlled global study evaluating the safety and efficacy of Soliris in 125 generalized myasthenia gravis patients who failed to respond to immunosuppressive treatments (refractory disease). They were randomized to receive either Soliris or a placebo for 26 weeks.
Although the trial did not achieve significance in its primary endpoint, which was a change in myasthenia gravis activities of daily living (MG-ADL) score, it did show a clinically meaningful reduction in disease severity in treated patients compared those on placebo on secondary measures. For example, substantial improvements were observed in the myasthenia gravis composite (MGC) score and the 15-item myasthenia gravis quality of life (MG-QOL15) score.
Alexion then initiated Phase 3 open-label extension study (NCT02301624) to assess Soliris’ long-term safety and efficacy in patients who had taken part in REGAIN. An interim analysis of this ongoing study, released by Alexion in September 2017, indicated sustained benefits after 52 weeks of additional treatment for the non-placebo group, and “rapid, significant, and sustained improvements” through 52 weeks in patients who started on Soliris in this extension study. Safety findings were also consistent with those found in REGAIN.
The Phase 3 extension trial is expected to conclude in January 2019.
Side effects associated with Soliris use include headache, dizziness, fever, nausea, infections, fatigue, bladder pain, and the common cold.
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