The complement C5 inhibitor eculizumab was effective in reducing disease severity and improving activities of daily living scores in adolescents with refractory generalized myasthenia gravis (MG), according to findings presented in April at the AAN Annual Meeting.
The drug is already approved for adults with MG. If approved for adolescents, eculizumab would be a new option for patients who have not had their disease controlled with other therapies, said Glen Frick, MD, PhD, executive medical director in neurology and ophthalmology therapeutics at Alexion Pharmaceuticals, which developed the drug.
The findings come from a phase 3, open-label study in adolescents aged 12 to 17, who had refractory disease after a year or more of immunosuppressive treatment; the patients required immunoglobulin or plasma exchange or were deemed by their physician to have had refractory symptoms. Eleven patients were enrolled, six of whom were receiving chronic intravenous immunoglobulin G (IVIg). Ten completed the primary evaluation period.
Patients were infused with a weight-based dose every other week. The least squares mean change on the Quantitative Myasthenia Gravis total score at 26 weeks was a drop of 5.8 points compared to baseline (p=0.0004). The MG-Activities of Daily Living total score dropped 2.3 points (p=0.0017).
Treatment-emergent adverse events were mild to moderate and no meningococcal infections, Dr. Frick said, adding that patients were required to have meningococcal vaccines.
The availability of eculizumab could help adolescents avoid having to take corticosteroids, which can cause diabetes, weight gain, high blood pressure—and, in adolescents, can stunt growth.
Dr. Frick said the goal is avoid treating adolescents with corticosteroids as much as possible. “We're hoping eculizumab will provide patients with refractory myasthenia the option of a potentially steroid-sparing treatment that will hopefully improve their quality of life in terms of school activities and daily functioning."
He acknowledged the potential difficulty of needing to visit an infusion center every two weeks. Even in the clinical trial, keeping up with that schedule was not always easy, he said
“We appreciate that for parents and families, it is not always easy to maintain such a schedule amid school, vacations, and other activities," Dr. Frick said, noting that sometimes a home visit was required to keep the treatment on schedule. “However, we're hopeful to potentially offer an option that may enable them to participate in these activities and live their lives more fully."
The C5 inhibitor ravulizumab is also under study with Alexion and is a slightly different formulation that requires dosing only every eight weeks, he said.
Richard Nowak, MD, MS, assistant professor of neurology at Yale School of Medicine and chief medical advisor to the Myasthenia Gravis Foundation of America (MGFA), said options for pediatric patients with generalized MG are limited, mainly due to their side effects, as with corticosteroids and azathioprine.
“This study represents a step forward in potentially having an additional option available for this population where we don't really have good alternative strategies, especially in cases of MG that is difficult to control," he said.
He pointed to a 2022 study on rituximab in a child population, in which researchers found better results with rituximab as a first-line therapy compared with conventional immunosuppressive drugs. Nonetheless, additional evidence-based options would be welcome and important to have available as the MG treatment paradigm evolves with a greater emphasis on precision health, he said.
He added that he would like to see data on quality of life and additional clinical outcome details.
“This study offers data in support of clinical benefit and is an extension of findings seen in adult trials although it is a very small study," he said. “Furthermore, (it) provides data on safety, during a limited follow-up period. Whether or not the trial provides enough data for a labeling indication by the FDA for eculizumab in this population is unclear."
Nancy Kuntz, MD, medical director of the Mazza Foundation Neuromuscular Program at Lurie Children's Hospital and an investigator at a trial site, said she is excited about “this new wave of translational science regarding treatment of myasthenia gravis as it targets the specific immune mechanism activated by the self-directed antibodies in MG—which for eculizumab is the complement step in the immune cascade."
Dr. Kuntz said she is looking forward to avoid to having to use broad immunosuppression, she said.
The every-other-week IV infusion requirement “does create a practical burden for children and families," she said. “However, if the treatment allows the child or adolescent to maintain normal function and prevents breakdown of neuromuscular junctions/muscle, it is worth it."
Dr. Frick has received personal compensation for serving as an employee of AstraZeneca/Alexion Rare Disease. Dr. Frick has stock in AstraZeneca/Alexion Rare Disease.