Nipocalimab, a FcRn blocker, significantly improved symptoms and reduced immunoglobulin autoantibody levels in patients with myasthenia gravis.
Myasthenia gravis is a rare chronic autoimmune and neuromuscular disease that affects the communication between nerves and muscles. These patients may experience symptoms such as droopy eyelids, double vision, and difficulty chewing, swallowing, breathing, and walking, among others. The rarity of the condition makes it challenging for patients to find providers who are not only aware of the disease but are also updated on the latest treatment options. Results of a recent phase 2 trial demonstrated that nipocalimab, a neonatal Fc receptor (FcRn) blocker, significantly improved symptoms, and reduced immunoglobulin autoantibody levels in this patient population.
In an interview with HCPLive, Sindhu Ramchandren, MD, Director of Clinical Development and Clinical Leader, Neuroscience, Janssen, discussed the clinical significance of these results and the therapeutic impact nipocalimab could make on patients living with this rare condition.
“To understand myasthenia gravis, you're to understand how the immune system works,” Ramchandren stated. “In a very simplistic sense, the way I explain to my kids, is that your body produces immune cells to fight off infections. And the way your immune system recognizes foreign bodies is that it recognizes parts of the bacteria or the viruses as foreign to itself, and forms an immunoglobulin, an antibody that binds to it. When then your body sees this bound complex, it recognizes it as foreign and destroys it.”
However, for those with autoimmune diseases, the body recognizes itself as foreign and begins to form autoantibodies. In patients with myasthenia gravis, autoantibodies form in the neuromuscular junction, the space between the nerve connecting to the muscle, and disrupts the transmission of signals from the nerves to the muscles.
“For so long, the standard of care of dealing with these kinds of autoantibody mediated diseases is just a blanket immunosuppression,” Ramchandren explained. “You reduce the immune system so that it doesn't make any autoantibodies. But the immune system does a lot of good things as well. The problem is that it's producing these bad autoantibodies, not that it's not producing autoantibodies in general. We need a finer balance between allowing your immune system to still function while targeting the disease in myasthenia gravis, Chronic inflammatory demyelinating polyneuropathy (CIPD), and other autoantibody mediated diseases.”
Nipocalimab may be a promising new treatment option for these conditions.
“This is a perfect kind of balance because it allows the immune system to still produce immunoglobulins, still function, but lowers the level of the autoantibodies,” Ramchandren emphasized. “We have the proof of concept with our phase 2 trial in myasthenia gravis where we were able to show that treatment with nipocalimab resulted in a significant reduction in the immunoglobulin autoantibody levels. And this also translated to improved symptoms of their activities of daily living.”
The phase 2 trial underscored the hypothesis that reducing autoantibody levels would improve symptoms in these patients. It also reported comparable adverse events between patients receiving nipocalimab and the placebo cohort, indicating that it is a safe and well-tolerated drug. The ongoing larger, phase 3 study, which is currently enrolling patients, will hopefully reinforce these results.
“I used to be a neuromuscular physician prior to joining industry,” Ramchandren started. “One of the challenges I always faced as a physician is that our current standard of care, which are steroids and broad immunosuppressants, typically chemotherapy drugs, are so broad and so powerful that they suppress your entire immune system. They predispose a patient to infections that they can’t fight off because the immune system is suppressed. There are a host of other side effects as well.”
She noted that the other issue with prescribing immunosuppressants is the prolonged time it takes, typically months or even years, before it starts working. With this new class of medicine, patients can see improvements within up to 2 weeks of initiation. These results were sustained throughout the study.
“This is especially important in children and women of childbearing potential, because in both of those groups, these kinds of immunosuppressants are not the best course of action due to the long-term consequences, such as broad toxicity,” Ramchandren stated. “To have a very targeted mechanism of action, like nipocalimab, opens up avenues for new treatment for these patients.”