Houston Methodist is leading a clinical trial to collect real-world data about the effectiveness and safety of a revolutionary new class of drugs, C5 inhibitors, that is providing new hope for patients with myasthenia gravis (MG), a rare autoimmune disease that affects muscle strength.

C5 inhibitors represent a major advancement in the treatment of MG, which often present significant challenges in daily life for the estimated 36,000 to 82,000 U.S. people with the condition. By inhibiting the C5 protein, the medications prevent the immune system from attacking healthy muscle tissue, thereby reducing the debilitating muscle weakness characteristic of MG.

"C5 inhibitors have shown tremendous promise in clinical trials, offering an effective treatment option for patients with myasthenia gravis who have not responded well to traditional therapies," said Dr. Ericka Greene, leading expert researcher and professor of clinical neurology at Houston Methodist Hospital.

Traditional treatments for the disease include anticholinesterase agents, immunosuppressants, plasmapheresis and intravenous immunoglobulin. While these can be effective for some, they do not work for everyone and can cause severe side effects.

In contrast, C5 inhibitors, such as eculizumab, ravulizumab and zilucoplan, have been shown to significantly improve muscle strength and reduce fatigue in MG patients. They work by targeting a crucial part of the body's immune response known as the complement system, a breakthrough made possible by an improved understanding of the underlying mechanisms of MG.

The disease occurs when the immune system produces antibodies that attack acetylcholine receptors at the neuromuscular junction, impairing muscle contraction. The complement system is activated in this process, leading to further damage. By blocking the C5 protein, the inhibitors prevent the formation of the membrane attack complex, which is responsible for much of the immune-mediated damage in MG.

The first C5 inhibitor to receive FDA approval for MG was eculizumab (Soliris) in 2017. Previously approved to treat a rare blood disorder called paroxysmal nocturnal hemoglobinuria, eculizumab arrests the formation of the membrane attack complex, thwarting an immune response at the muscle endplate.

In 2022, ravulizumab (Ultomiris) was approved by the FDA for the treatment of anti-acetylcholine receptor (AChR) antibody-positive generalized MG which accounts for 80% of the total number of patients with the disease. The first FDA-approved long-acting complement C5 inhibitor for the treatment of MG, it possesses a similar mechanism of action to eculizumab but requires less frequent dosing.

In October 2023, the FDA approved zilucoplan (Zylbrysq) to treat generalized MG in adults. It is the first once-daily subcutaneous C5 inhibitor to be approved for the condition.

But according to the Houston Methodist trial description, a need still exists for the collection of real-world data on effectiveness, safety and patterns of drug utilization for these drugs to complement the body of scientific evidence and better inform current and future clinical practice. There is no current source that collects adequate data on patients with MG treated with C5 inhibition therapy in the standard clinical practice setting in the U.S.

The prospective trial is a long-term, observational registry. It is schedule to go through 2029.

"Our goal is to provide patients with treatments that not only manage symptoms but also improve their quality of life," Dr. Greene said. "With complement inhibitors, patients who had accepted suboptimal living for many years can now return to work, attend PTA meetings and travel with family. They no longer need to rest while brushing their hair because their arms have become so fatigued."

Despite the success of these new C5 inhibitors, Dr. Greene acknowledges that combination treatments are often necessary. "While C5 inhibitors are a significant breakthrough, many patients still require additional therapies to fully manage their symptoms," she said.

Dr. Greene is committed to raising awareness about MG and educating both health care professionals and patients about the latest advances in treatment. She directs the neuromuscular residency fellowship at Houston Methodist and co-directs the Annual Myasthenia Gravis Patient Education Conference.

"This is an important era for myasthenia gravis," Greene emphasized. "With groundbreaking treatments like C5 inhibitors, the outlook for patients continues to improve, and we are committed to furthering this research and providing the best possible care."

For a more detailed look at Dr. Greene's research and the processes driving myasthenia gravis' attack on healthy muscle tissue, click here to read the full article in our sister publication Methodology.