FDA: Soliris is Approved to Treat Generalized MG in the United States


Alexion Pharmaceuticals announced Oct. 23, 2017, that the U.S. Food and Drug Administration (FDA) has approved eculizumab (brand name Soliris) as a treatment for adults with generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor antibody-positive. Soliris is the first in a new class of drugs to be approved for MG in the U.S.

Soliris is not a cure, but it may lessen the symptoms experienced by people living with generalized MG.

Soliris was tested in clinical trials in people who had previously failed immunosuppressive treatment and continued to suffer from significant unresolved disease symptoms such as difficulties seeing, walking, talking, swallowing and breathing. Participants taking Soliris had improved scores on scales designed to assess quality of life and symptom burden including double vision, ptosis (drooping of the eyelids), swallowing, speech, breathing, and use of arms and legs.

Generalized MG affects a subset of MG patients

People with generalized MG experience muscle weakness in the head, neck, trunk, limb and respiratory muscles. An estimated 10-15 percent do not respond to treatments that are typically helpful in other MG patients.

Profound weakness throughout the body often is accompanied by slurred speech, impaired swallowing and choking, double vision, upper and lower extremity weakness, disabling fatigue, shortness of breath due to respiratory muscle weakness, and episodes of respiratory failure.

People with generalized MG may require hospitalization, often involving intensive care unit stays.

Soliris is designed to prevent destruction of the neuromuscular junction

Soliris is a terminal complement inhibitor that targets a part of the immune system called the complement system, which is responsible for helping antibodies clear damaged cells and potentially toxic microbes that could cause infections. In MG, antibodies whose job it is to target these toxic pathogens, instead inappropriately recruit the complement system and target the space across which nerve fibers transmit signals to muscle fibers, called the neuromuscular junction (NMJ).

In people with anti-acetylcholine receptor antibody-positive MG, the body’s own immune system turns on itself to produce antibodies against the acetylcholine receptor, a receptor located on muscle cells at the NMJ. The inappropriate binding of antibodies to acetylcholine receptors activates the complement system, which leads to a localized destruction of the NMJ. As a result, the communication between nerve and muscle is impaired, which in turn leads to a loss of normal muscle function.

Soliris is thought to work in MG by inhibiting the complement pathway to prevent destruction of the NMJ.

Treatment with Soliris will not cure generalized MG, but it may improve disease symptoms, the ability to carry out activities of daily living and quality of life.

REGAIN clinical trial tested Soliris for MG

The phase 3 REGAIN study tested Soliris in people with generalized MG who had previously failed immunosuppressive treatment and continued to suffer from significant unresolved disease symptoms such as difficulties seeing, walking, talking, swallowing and breathing, and who also had an MG-ADL score of greater than or equal to 6. (The Myasthenia Gravis – Activities of Daily Living profile, or MG-ADL, is a patient-reported index of daily living assessment; a score greater than 6 suggests that activities of daily living are moderately/severely impacted by MG.) Patients enrolled in the trial also had to test positive for the presence of acetylcholine receptor antibodies.

Participants were treated over a period of 26 weeks either with Soliris or placebo. Those who were treated with the drug received a 900-milligram weekly infusion for four weeks, followed by a 1,200-milligram infusion of Soliris one week later, and then a 1,200-milligram infusion of Soliris every two weeks.

Treatment effects were measured across four MG-specific assessment scales (MG-ADL, Quantitative Myasthenia Gravis [QMG], MG Composite [MGC] and MG Quality of Life 15 [MG-QoL 15]). The Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) is a categorical scale that assesses the impact on daily function of eight signs or symptoms that are typically affected in generalized MG. Each item is assessed on a 4-point scale, where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function (total score 0-24). A statistically significant difference favoring Soliris was observed in the mean change from baseline to Week 26 in MG-ADL total scores (-4.2 points in the Soliris treated group compared with -2.3 points in the placebo-treated group).

Clinically meaningful improvements in several secondary measures were observed in patients treated with Soliris compared with those who received a placebo, including an improvement in the QMG score, a physician-administered test that assesses MG severity. The QMG scale ranges from 0 to 39, with a higher score representing more severe impairment. The scale assesses symptoms such as double vision, ptosis (drooping of the eyelids), swallowing, speech, breathing, and use of arms and legs. At 26 weeks following the start of Soliris, participants in the REGAIN trial showed an average 4.6-point reduction in the QMG score from baseline, as compared to patients taking placebo who experienced an average 1.7-point reduction on the scale.

The effects of Soliris were also investigated in an open-label extension trial of REGAIN where the beneficial effects of Soliris were found to be maintained at 52 weeks after the start of treatment. Participants who originally were in the placebo group of REGAIN also saw benefits from taking Soliris after 26 weeks of treatment.

Soliris has previously been approved in the U.S. for the treatment of rare blood diseases. The U.S. prescribing information for Soliris includes the following warnings and precautions: Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. In patients with generalized MG who are anti-acetylcholine receptor antibody-positive, the most frequently reported adverse reaction observed with Soliris treatment in the placebo-controlled clinical study was musculoskeletal pain.

MDA has invested in previous basic research studies investigating complement inhibition as a therapeutic strategy for MG and is currently funding studies aiming to develop improved complement inhibitor drugs for MG.

For more information

If you are interested in adding Soliris to your treatment regimen, you should speak first with your health care provider, who will initiate treatment (if appropriate).

You may learn more by visiting the Soliris website (http://gmg.soliris.net/) or speaking with a Nurse Case Manager through OneSource, a personalized patient support system from Alexion (the manufacturer of Soliris). The Alexion Nurse Case Managers are there to help you with answers to your questions about Soliris. Contact OneSource at 1-888-SOLIRIS.

Be sure to check back at mda.org for updates as they become available.