The April 30 FDA approval of nipocalimab-aahu (Imaavy; Johnson & Johnson) for generalized myasthenia gravis (gMG) in adult and pediatric patients 12 years or older marked a significant advancement in treating this chronic neuromuscular disease. To break down what this means for these patients and clinicians, The American Journal of Managed Care® (AJMC®) spoke with Constantine Farmakidis, MD, a neuromuscular specialist and associate professor at the University of Kansas Medical Center, whose expertise lies in MG and related neuromuscular junction disorders.
Farmakidis explains how nipocalimab—a neonatal Fc receptor (FcRn) blocker—works to rapidly reduce harmful antibodies driving gMG symptoms and offers a targeted alternative to broad immunosuppressants. He discusses key findings from the pivotal Vivacity-MG3 (NCT04951622) trial, including early symptom relief and sustained benefits, while addressing practical considerations like administration and safety. Notably, nipocalimab’s approval covers a broad patient population, both anti–acetylcholine receptor positive (AChR+) and anti–muscle-specific kinase antibody positive (MuSK+) subtypes, as well as adolescents.
Read on for insights into how nipocalimab fits into the evolving gMG treatment landscape and its potential to improve daily function for patients with this challenging condition.
This transcript has been lightly edited for clarity.
AJMC: Can you briefly explain the mechanism of action of FcRn blockers, such as nipocalimab, and why this class of medications is particularly effective in treating gMG?
Farmakidis: Nipocalimab is a neonatal FcRn blocker that inhibits the recycling and recirculation of immunoglobulin G (IgG) antibodies and ultimately leads to a broad knockdown of IgG levels in the body. Myasthenia gravis is an IgG autoantibody–mediated disease—and in patients who have gMG, nipocalimab broadly decreases their IgG levels—but this also includes disease-causing IgG autoantibodies like the AChR antibody and the MuSK antibody. It is through this antibody removal mechanism that nipocalimab treats MG.
The phase 3 Vivacity-MG3 study of nipocalimab in patients with gMG was pivotal, showing that treatment with nipocalimab leads to improved disease control and that the medication is well tolerated in a broad population of patients.
There is another category of recently developed biologic agents that treat MG by inhibiting the terminal portion of the complement system. There is no evidence to date that FcRn blockers are more effective than terminal complement inhibitors for MG treatment.
AJMC: Mechanistically, what differentiates nipocalimab from other currently approved FcRn inhibitors for gMG?
Farmakidis: Nipocalimab is a fully human, nonglycosylated IgG1 isotype monoclonal antibody that blocks the neonatal Fc receptor. Rozanolixizumab (Rystiggo; UCB) is a humanized monoclonal antibody that is also designed to block the neonatal FcRn and inhibit antibody recycling; it is of the IgG4 isotype.
Efgartigimod (Vyvgart; Argenx), unlike nipocalimab and rozanolixizumab, is not a full antibody but a portion of an antibody known as a fragment. This drug is derived from the Fc fragment portion of an IgG1 humanized antibody that is also a neonatal FcRn blocker.
AJMC: Nipocalimab is described as immunoselective, sparing other adaptive and innate immune functions. How does this characteristic differentiate its safety and tolerability profile?
Farmakidis: Nipocalimab is intended to knock down IgG antibody levels. This could be anticipated to interfere with antibody-mediated or humoral immunity. However, clinical trial data indicate mild suppression of humoral immunity. On the other hand, nipocalimab and other neonatal FcRn blockers do not interfere with the complement system or interfere with cell-mediated immunity, as can be seen with other immunosuppressant medications such as prednisone.
Constantine Farmakidis, MD | Image Credit: University of Kansas Medical Center
AJMC: The Vivacity-MG3 trial demonstrated rapid IgG reduction and symptom relief as early as week 2. How clinically meaningful is this swift onset of response for patients and their management?
Farmakidis: Clinical trial data for nipocalimab in MG show both early drops in serum IgG levels and simultaneous improvement in disease control, as seen in MG clinical trial outcome measures. This is encouraging, because traditional medications like immunosuppressants or steroids can take months to show effect, although it should be noted that each patient will have an individualized response to an FcRn blocker, and both the clinical effect and time of onset of any benefit may not match aggregated clinical trial results.
AJMC: How should clinicians interpret the observed changes in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores seen in the Vivacity-MG3 trial in terms of their tangible impact on patients’ daily functioning and quality of life?
Farmakidis: A 2-point change in the MG-ADL scale is considered clinically significant, while a 3-point change in the QMG score is generally considered clinically significant. The clinical trial in myasthenia gravis showed statistically significant improvement in the nipocalimab-plus-standard-of-care group vs those who only received standard of care for both the MG-ADL and QMG outcome measures.
AJMC: Considering the inclusion of patients refractory to standard of care in Vivacity-MG3, what do these findings reveal about nipocalimab’s potential role in managing treatment-resistant gMG?
Farmakidis: Individual outcomes with nipocalimab therapy for patients who previously were treatment refractory cannot be projected from the aggregate outcomes of a clinical trial with about 75 patients in each of the nipocalimab and placebo groups. However, since this was a positive trial in a group of patients with gMG who were on background treatments and still had moderate to severe symptoms, this could be taken as an indication that nipocalimab is a promising treatment option for patients.
AJMC: What are the practical administration considerations for nipocalimab, particularly for diverse patient populations such as adolescents or those with mobility limitations?
Farmakidis: Nipocalimab is administered as an intravenous (IV) infusion every 2 weeks. Patients should be able to travel or obtain transportation to an infusion center, although it is possible that nipocalimab may become available through home infusions as well. Individuals should also have veins that are consistently accessible or be amenable to port placement or an equivalent medical device that allows for consistent and uncomplicated IV access.
AJMC: What realistic day-to-day functional improvements can patients anticipate with nipocalimab therapy?
Farmakidis: Patients with MG can have ocular, lower face, limb, and respiratory muscle weakness. Any of these can improve if the individual patient is responsive to nipocalimab.
AJMC: The open-label extension data indicate sustained disease control with benefits lasting up to 20 months (72 weeks). Could you discuss the clinical importance of this long-term durability for managing gMG’s fluctuating and often unpredictable nature?
Farmakidis: The treatment goal in MG is to first achieve disease control and then to have disease control be durable. The open-label extension data for nipocalimab in MG showed evidence of durable disease control. This is a very encouraging finding.
AJMC: What further insights do you anticipate from even longer-term data?
Farmakidis: Postapproval clinical data are likely to provide critical information about the long-term safety and tolerability of nipocalimab.
AJMC: Given its favorable safety profile, what are the key adverse effects and monitoring requirements clinicians and patients should be aware of when using nipocalimab?
Farmakidis: Infections were not observed at a higher rate in the nipocalimab group vs the placebo group. However, given nipocalimab’s immune-driven mechanism of action, it remains important to monitor patients for severe infections. There are other adverse effects listed in the product insert, and these should also be monitored as well.
AJMC: Nipocalimab’s approval now encompasses the broadest FcRn-treated population, including both anti–AChR+ and anti–MuSK+ subtypes, as well as adolescents. Can you discuss the clinical significance of having a single FcRn inhibitor for this expanded population, how it impacts current treatment paradigms, and your confidence in its use for adolescents?
Farmakidis: In my view, it is significant that an additional drug such as nipocalimab is now approved for use in patients who are AChR antibody-positive and MuSK antibody-positive—essentially, the more options available, the better for patients. At this time there is no basis to say that nipocalimab may be superior to other FcRN blockers or terminal complement inhibitors, as no clinical trials have been done to compare the effectiveness of these drugs. As for the approval for adolescents, it is highly notable, as this is the first biologic agent approved in this age group. Here nipocalimab will provide an FDA-approved corticosteroid-sparing treatment option.
