The basis for the FDA’s decision came from the phase 3 ADAPT-SC study, in which subcutaneous efgartigimod showed a slightly better ability to reduce immunoglobulin compared with its previously approved intravenous formulation.
The FDA has approved a subcutaneous formulation of efgartigimod (Vyvgart; argenx)—officially known as efgartigimod alfa and hyaluronidase-qvfc—as a treatment for adult patients with generalized myasthenia gravis (gMG) who are antiacetylcholine receptor (AChR) antibody positive. Marketed as Vyvgart Hytrulo, the therapy’s approved indication is for a 1008-mg fixed dose administered over 30 to 90 seconds in cycles of once-weekly injections for 4 weeks, offering patients a new way to receive treatment for their condition.1
The decision was based on the phase 3 ADAPT-SC study (NCT04735432), which evaluated the noninferiority of the pharmacodynamic profile effect of subcutaneous efgartigimod as compared with the previously approved intravenous (IV) administration. ADAPT-SC, a trial that featured 110 individuals with gMG, met its primary end point of change in total immunoglobulin (IgG) reduction over a 29-day period.
“Today’s approval of Vyvgart Hytrulo is another significant milestone on our path to redefine what well-controlled means for gMG patients. The availability of a second argenx innovation in just 18 months also underscores our longstanding commitment to the gMG community by providing more choice and flexibility in how patients receive treatment,” Luc Truyen, MD, PhD, the chief medical officer of argenx, said in a statement.1 “With our broad gMG offering of both a first-in-class infusion and SC injection, we continue to offer an individualized treatment approach and [the] possibility of staying symptom-free, while providing patients options of how and where they want to seek treatment. We want to thank the gMG patient community and their supporters, clinical investigators, our employees, and all stakeholders who have collaborated with us to advance this subcutaneous option, including our partners at Halozyme."
Efgartigimod’s subcutaneous form is coformulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE drug delivery technology, which allows for subcutaneous delivery of biologics that are typically administered via infusion.
In the trial, the pharmacodynamic effect of percent change in total IgG levels were assessed 1 week after the last dose of IV or subcutaneous efgartigimod. Inclusion criteria of the trial were the same as the phase 3 ADAPT trial (NCT03669588) of IV efgartigimod, which served as the basis for the original approval. Enrolled patients had a confirmed gMG diagnosis and an Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of at least 5 with greater than 50% of the total score attributed to non-ocular symptoms, at screening and baseline.
Patients in the study were on a stable dose of at least 1 gMG treatment prior to randomization, including acetylcholinesterase (AChR) inhibitors, corticosteroids, or nonsteroidal immunosuppressive drugs, and were required to remain on that stable dose throughout the primary trial. Eligibility into ADAPT-SC did not depend on antibody status, and included both patients with and without AChR antibodies. The total study duration was approximately 12 weeks, including 7 weeks of follow-up after the treatment cycle.
“The clinical trials of Vyvgart continue to show significant benefit to patients with a favorable safety profile and clear improvements in gMG disease scores. Now with the approval of Vyvgart Hytrulo, we have a broad gMG treatment offering with both IV and [subcutaneous] administration options and can select based on patient needs and preference without sacrificing clinical benefit or safety,” James F. Howard Jr., MD, a professor of neurology at the University of North Carolina at Chapel Hill School of Medicine and the principal investigator for the ADAPT-SC trial, said in a statement.1
In ADAPT-SC, subcutaneous formulation of efgartigimod was associated with a mean total reduction in IgG of 66.4% at day 29 compared with 62.2% with the IV formulation (P <.0001 for noninferiority). These results were consistent across the overall study cohort and were no different between patients with or without AChR antibodies. Supplementary key secondary end points were also met, and were consistent with the efficacy results observed in ADAPT. On MG-ADL scores, 69.1% of those treated with the subcutaneous form were deemed responders, having at least a 2-point improvement for 4 consecutive weeks.2
Additionally, 65.5% of those treated with the new formulation were responders on the Quantitative Myasthenia Gravis (QMG) scoring, having displayed at least a 3-point improvement on the QMG score for a minimum of 4 consecutive weeks. As well, the observations of onset of effect and minimal symptom expression—defined as an MG-ADL score of 0 or 1—were also consistent with ADAPT findings. Efgartigimod’s subcutaneous form also showed a consistent safety profile with the phase 3 findings from the IV form. Overall, it was generally well-tolerated, with the most frequent adverse event being injection site reactions (ISRs), all of which were considered mild to moderate and resolved over time.
"We are pleased that argenx has received FDA approval for the subcutaneous form of efgartigimod, which reinforces their commitment to the patient community with a broadening of treatment options that brings flexibility for patients," Helen Torley, MBChB, MRCP, president and chief executive officer of Halozyme, said in a statement.4 "We look forward to the multiple data readouts this year for subcutaneously administered efgartigimod in additional autoimmune conditions, with the potential to expand the number of approved indications and eligible patients."
The IV formulation of efgartigimod was approved by the FDA in December 2021, using results from ADAPT as the basis for the decision. Findings of that study suggested that efgartigimod was well-tolerated and efficacious in treating patients with gMG, with the drug meeting the primary end point by improving MG-ADL scores for patients with AChR-Ab+ gMG compared with those in the placebo group (67.7% vs. 29.7%; P <.0001). Additionally, 40.0% of efgartigimod-treated AChR-Ab+ patients achieved minimal or no symptoms compared with 11.1% treated with placebo.