#AANAM – Nipocalimab Safely Eases gMG Symptoms, Final Trial Data Confirm
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Janssen’s experimental therapy nipocalimab (M281) safely, rapidly, and effectively reduced disease severity in adults with generalized myasthenia gravis (gMG), according to final data from the Phase 2 Vivacity-MG trial.
“The utility of currently available [MG] medicines is limited, and many patients fail to adequately respond. This may lead to uncontrolled symptoms or significant side effects, resulting in an impact on not only their daily lives but their families and caregivers as well,” Luc Truyen, MD, PhD, global head of development and external affairs at Janssen’s Research and Development, said in a press release.
“The results from the Phase 2 Vivacity-MG study are promising, and we look forward to continuing to advance nipocalimab to Phase 3 clinical trials in gMG in the near future,” Truyen added.
These findings add to previously reported top-line data showing the therapy was well-tolerated and resulted in significant reductions in MG symptoms.
Full trial results were detailed by Jeffrey Guptill, MD, a trial investigator at Duke University Medical Center, in an oral presentation at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting, held online April 17–22.
The presentation was titled, “Vivacity-MG: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Nipocalimab Administered to Adults with Generalized Myasthenia Gravis.”
Nipocalimab is an antibody designed to address the underlying cause of MG by preventing interaction between a receptor molecule called FcRn, and immunoglobulin G (IgG) antibodies, including those that drive MG development.
Given that FcRn-IgG binding prevents IgG degradation and prolongs the time these antibodies remain in the bloodstream, nipocalimab is expected to lower the levels of both total IgG and disease-associated IgG autoantibodies, ultimately easing MG severity.
The international Phase 2 Vivacity-MG study (NCT03772587) evaluated nipocalimab’s safety, tolerability, pharmacokinetics (movement into, through, and out of the body), pharmacodynamics (effects on the body), and effectiveness in 68 adults with moderate-to-severe gMG.
All participants had an insufficient response to ongoing standard-of-care therapy, and were randomly assigned to one of four nipocalimab regimens — 5 or 30 mg/kg every four weeks, 60 mg/kg every two weeks, or 60 mg/kg as a single dose — or to a placebo for eight weeks (two months).
Each group contained 13 to 14 patients, and all received a total of five intravenous infusions of either nipocalimab or placebo every other week during the treatment period. Those in groups whose treatment did not follow the two-week dosing schedule received placebo infusions in between in order to maintain secrecy of the assigned treatment regimen. All enrolled also continued to receive standard-of-care treatment.
There were no major demographic and clinical differences between nipocalimab and placebo groups at the study’s start, except for disease duration, which was slightly longer in the placebo group, Guptill noted. More than 90% of the patients had IgGs against the AChR protein, the most common target of disease-associated antibodies in MG.
After completing the trial, participants were given the option to enroll in an open-label extension study (NCT03896295), in which all would be treated with nipocalimab.
Vivacity-MG’s main goal was to assess changes in the patient-reported MG Activities of Daily Living (MG-ADL) score, a validated measure of MG severity, and the rate of adverse events. Secondary goals included changes in muscle strength, quality of life, and total IgG levels in the blood.
Results showed a dose-dependent reduction in IgG levels among patients treated with nipocalimab — detected within the first week of treatment for most patients — but no major change in those given a placebo.
Participants treated with the highest nipocalimab dose (60 mg/kg) had an 80% drop in IgG levels, which was sustained in the group receiving the therapy every other week. Similar reductions were observed for IgG subclasses and anti-AChR autoantibodies.
These effects were associated with a dose-dependent drop in the MG-ADL score, indicative of lower disease severity, which was detected within the first two weeks in about 40% of patients — in agreement with the observed IgG level response.
Notably, IgG reductions were significantly associated with symptom lessening, as assessed with the MG-ADL score.
Interestingly, patients on either the 30 mg/kg dose of nipocalimab every four weeks, or the 60 mg/kg dose every other week had similar MG-ADL score reductions at day 57 post-treatment.
A significantly greater pooled proportion of nipocalimab-treated patients also showed a durable easing of symptoms (for at least one month) compared with those on a placebo (51.9% vs. 15.4%).
“Nipocalimab demonstrated a robust, rapid, sustained, and predictable clinical response that was observed as early as the first two weeks of treatment in all the dosing [groups],” and this response “was durable over the course of the study period,” Guptill said.
“A relationship between the degree of IgG lowering and the clinical benefit” was also evident, he added.
The therapy was generally well tolerated, with no adverse events leading to treatment discontinuation, no dose-dependent increase in adverse event rates, and no nipocalimab-related serious adverse events.
Adverse events “were relatively well balanced, including headaches and infections,” Guptill said, adding that no safety concerns were identified.