Nipocalimab Offers Hope for Patients with Generalized Myasthenia Gravis

Katie Abouzahr, MD

Credit: Fierce Biotech

Johnson & Johnson has submitted a Biologics License Application to the US Food and Drug Administration (FDA) for nipocalimab, a potential new treatment for generalized myasthenia gravis (gMG). This application is based on positive results from the Phase 3 Vivacity-MG3 study, which showed that nipocalimab, when added to standard care, provided sustained disease control and improvement in muscle weakness symptoms compared to a placebo. This makes it the first treatment of its kind to show such long-term effectiveness in certain antibody-positive patients.

In an interview with The Educated Patient, Katie Abouzahr, MD, vice president of the Autoantibody Portfolio and Maternal Fetal Disease Area Leader at Johnson & Johnson, emphasized the importance of this advancement, particularly given the high unmet need for people living with gMG. Nipocalimab has the potential to change how patients manage their symptoms and improve their quality of life.

Can you explain the significance of Johnson & Johnson's BLA for nipocalimab in treating gMG?

Katie Abouzahr, MD: Patients around the world need additional treatment options to help address the serious health consequences of myasthenia gravis. If approved, nipocalimab could potentially offer a new targeted therapy for patients with gMG. Both its ability to offer sustained disease control and unique molecular properties could lead to improved management of this challenging and unpredictable condition.

How does nipocalimab differ from existing treatments for gMG, and what makes it a promising option for patients?

KA: Nipocalimab is the first neonatal Fc receptor (FcRn) blocker to demonstrate sustained disease control in a broad population of antibody positive individuals, which account for approximately 95 percent of the gMG patient population. Individuals randomized to nipocalimab plus standard of care (SOC) saw improvement in their Myasthenia Gravis Activities of Daily Living (MG-ADL) scores, compared to placebo plus SOC, over six months of consistent dosing (every other week).

Nipocalimab is an FcRn blocker that blocks the recycling of Immunoglobulin G (IgG) and thereby lowers circulating IgG antibodies, including autoantibodies. In the Phase 3 Vivacity-MG3 study, IgG lowering was rapid, showing a reduction by week two of the trial. Moreover, IgG lowering was substantial and sustained with reductions in IgG of approximately 70% through the study's six-month endpoint. The magnitude of IgG lowering was generally associated with greater improvement in symptoms, suggesting a correlation between the reduction in IgG and clinical improvement in gMG.

More broadly, the investigational anti-FcRn blocker is currently being studied across three key segments: Rare Autoantibody (ranging from neurologic to hematologic), Maternal Fetal and Prevalent Rheumatic diseases, in multiple potential indications, each with high unmet need.

What is the importance of the Phase 3 Vivacity-MG3 study in supporting the application for FDA approval?

KA: The Phase 3 Vivacity-MG3 study, on which this application is based, was designed to measure the sustained efficacy and safety of nipocalimab with consistent dosing in gMG.

The data show that nipocalimab plus SOC achieved superiority over placebo plus SOC, as measured by the primary endpoint of improvement in the MG-ADL score from baseline over 24 weeks in antibody positive participants.

Based on these results, Vivacity-MG3 is the first study to demonstrate sustained disease control in these subtypes. It’s also worth noting that the safety and tolerability of nipocalimab were consistent with other studies.

Can you elaborate on the unmet medical needs for patients with gMG and how nipocalimab addresses those gaps?

KA: The SOC for gMG is associated with significant side effects or limited efficacy. There is still a need for immunoselective treatments with the potential to offer sustained disease control and better tolerability for people living with gMG. Researchers are exploring new approaches to treat this condition, including FcRn blockers. Potential treatments, like investigational nipocalimab, provide a therapeutic option with consistent dosing that does not require repeat clinical evaluation. Encouragingly, most adverse events in the Vivacity-MG3 study were mild or moderate in severity. There was no difference between nipocalimab and placebo in the incidence of overall infections, and the incidence of headache was also similar between the treatment arms.

From your perspective, what challenges do patients and healthcare providers currently face in managing gMG, and how might nipocalimab change the treatment landscape?

KA: People living with gMG often face significant challenges due to the debilitating nature of the disease. Initial disease manifestations are usually ocular but in 85% or more cases, the disease generalizes which is characterized by fluctuating weakness of the skeletal muscles leading to symptoms like limb weakness, drooping eyelids, double vision ,and difficulties with chewing, swallowing, speech and breathing. The symptoms can have a significant impact on quality of life, with 32% of individuals with gMG requiring help with daily activities and 39% reporting they experience comorbid depression. Finally, approximately 50% of people with gMG are unemployed.

Current treatments are limited in their effectiveness, and many patients do not respond adequately, leading to uncontrolled symptoms or significant side effects. Healthcare providers struggle with managing these patients due to the lack of highly effective treatment options that are available for chronic use and the need to balance efficacy with tolerability.

Based on clinical data, nipocalimab has the potential to improve the symptoms associated with gMG, prevent damage to neuromuscular junction and restore normal muscle function–offering new hope to patients, if approved.

What further research or clinical developments are needed to fully understand the potential of nipocalimab and FcRn blockers in autoimmune diseases like gMG?

KA: Clinical trials are essential to evaluate the long-term efficacy and safety of FcRn blockers in a broader population of gMG patients, including in pediatric populations. Additionally, it’s important to conduct comparative studies to understand how FcRn blockers and other treatments for gMG perform relative to one another.

More broadly, a better understanding of pathologic changes at the neuromuscular junction in patients experiencing an exacerbation of their gMG will also help further the body of evidence on the condition. This research may also help to elucidate the patients that could benefit the most from FcRn blockers, like nipocalimab, and optimize dosing regimens to maximize efficacy while minimizing side effects.

Is there anything else you’d like our audience to know?

KA: Johnson & Johnson has been deeply rooted in immunology and neuroscience for more than 60 years and has a legacy of developing innovations for a wide range of conditions with unprecedented unmet need. We are committed to tirelessly pushing the boundaries of research to deliver innovative and transformational approaches for autoantibody-driven diseases, including gMG. Johnson and Johnson’s extensive immunology experiencemakes it possible to apply novel science to map immune pathways and discover new connections, paving the way to address multiple diseases with similar underlying pathways.

We currently have a significant development program for nipocalimab. As I mentioned previously, nipocalimab is being studied across Rare Autoantibody, Maternal Fetal and Prevalent Rheumatic diseases, inmultiple potential indications.

I would like to recognize the teams who work so tirelessly to bring this medicine to patients. We really hope this will ultimately be transformative for patients and their families and I hope we get to continue the journey. I would also like to thank the patients who volunteer to be a part of our clinical trials, as their efforts help us identify new ways to improve the treatment landscape for all patients.