FDA expands approval for Vyvgart (efgartigimod alfa-fcab) and Vyvgart Hytrulo to include all serotypes of adult patients living with gMG – argenx

argenx SE announced the FDA approved a label expansion for Vyvgart (efgartigimod alfa-fcab) and Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for the treatment of adult patients with generalized myasthenia gravis (gMG). The approved supplemental Biologics License Application (sBLA) expands Vyvgart’s indication to include all serotypes of adult patients living with gMG – anti-AChR-Ab positive, anti-MuSK-Ab positive, anti-LRP4-Ab positive, and triple seronegative.

The approval is based on data from the Phase III ADAPT SERON study, the largest study to date of patients with gMG who do not have detectable anti-acetylcholine receptor antibodies (AChR-Ab) across three serotypes – anti-MuSK-Ab positive, anti-LRP4-Ab positive, and triple seronegative. The overall population of patients in the study treated with Vyvgart showed rapid, significant and sustained improvements in their gMG symptoms, including speech, vision, physical function and swallowing, among others. In addition, Vyvgart was well tolerated across serotypes, with safety consistent with the established profile in patients with anti-AChR-Ab positive gMG.

“Today’s approval means that all adult gMG patients, regardless of serotype, can now benefit from Vyvgart’s rapid onset, sustained disease control, and favorable safety profile,” said Luc Truyen, M.D., Ph.D., Chief Medical Officer at argenx. “For clinicians, this simplifies treatment decisions, representing a major advancement in reaching as many patients living with gMG as possible.”

“MG affects patients in various ways, and those with gMG who do not have detectable AChR antibodies need safe, effective treatments. Prior to the ADAPT SERON study, these patients were rarely included in clinical trials,” said James F. Howard Jr., M.D., Professor of Neurology (Neuromuscular Disease), Medicine and Allied Health, Department of Neurology, The University of North Carolina at Chapel Hill School of Medicine. “MG leads to debilitating muscle weakness, causing challenges with vision, movement, speech, swallowing, and even breathing. Although many MG patients have detectable AChR-Ab, roughly 20% do not, making diagnosis and management especially difficult. The expanded indication of efgartigimod for use in all adult gMG patients enables healthcare providers to prescribe this targeted treatment more readily upon clinical diagnosis, irrespective of serotype.”

Detailed results from the Phase III ADAPT SERON study:

• i) Patients showed clinically meaningful improvements in disease activity across all three serotypes – anti-MuSK-Ab positive, anti-LRP4-Ab positive, and triple seronegative.
• ii) The primary endpoint was met (p=0.0068), demonstrating that patients treated with Vyvgart achieved a statistically significant improvement in MG-ADL (Myasthenia Gravis Activities of Daily Living) total score compared to placebo at week 4.
• iii) In the overall population – across all serotypes in the study – mean change from baseline in patients treated with Vyvgart was a clinically meaningful 3.35-point improvement in MG-ADL total score at week 4.
• iv) Improvements in MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were observed across subsequent treatment cycles in the overall population and in all serotypes studied.
• v) Vyvgart was well tolerated across serotypes, with safety consistent with the established profile in patients with anti-AChR-Ab positive gMG.

“For too long, gMG patients who do not have detectable AChR-Ab have been left behind, feeling disengaged and excluded from receiving treatments that specifically treat their disease, which has led to patients experiencing a higher burden of suffering,” said Allison Foss, Executive Director of the Myasthenia Gravis Association. “This approval validates that gMG patients without AChR-Ab can benefit from a targeted treatment, bringing a sense of hope to thousands in our community.”

argenx recently announced positive top-line results from the ADAPT OCULUS study of Vyvgart Hytrulo in ocular MG and remains focused on advancing the development of Vyvgart for all patients living with MG, including pediatric gMG patient populations in the ADAPT Jr study.

ADAPT SERON Study Design

The Phase III ADAPT SERON study is a randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of efgartigimod in adults with anti-AChR antibody negative gMG (n=119) across North America, Europe, China, and the Middle East. Part A randomized participants (1:1) received 4 once-weekly infusions of efgartigimod IV or placebo, followed by a 5-week follow-up. Part B is an open-label period: participants receive 2 fixed cycles of 4 once-weekly efgartigimod infusions (4-week interval between cycles); from cycle 3 onward, additional cycles could be started ≥1 week after the last administration of the previous cycle, based on clinical status. The primary endpoint is the MG-ADL total score change from baseline to week 4 (day 29) in part A. Other scales of evaluation include QMG, MG-QoL 15r, MGC, and EQ-5D-5L VAS. Enrolled participants had a confirmed MG diagnosis by an independent panel of experts, and an MG-ADL total score of 5 or greater. Participants were on a stable dose of at least one gMG treatment prior to randomization, including acetylcholinesterase inhibitors, corticosteroids or nonsteroidal immunosuppressive drugs. Participants were eligible to enroll in ADAPT SERON if they were anti-AChR antibody negative gMG, which included participants who are anti-MuSK-Ab positive, anti-LRP4-Ab positive, and triple seronegative.

MG-ADL is a validated measure of disease activity in patients living with MG, which evaluates the functional impact of symptoms on daily activities such as speaking, chewing, swallowing, breathing, and limb strength.