argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced positive topline data from the Phase 3 ADAPT-SC study evaluating subcutaneous (SC) efgartigimod (1000mg efgartigimod-PH20) for the treatment of generalized myasthenia gravis (gMG). SC efgartigimod achieved the primary endpoint of total IgG reduction from baseline at day 29, demonstrating statistical noninferiority to VYVGART® (efgartigimod alfa-fcab) intravenous (IV) formulation in gMG patients. Based on these results, argenx plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) by the end of 2022.
SC efgartigimod is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology. ENHANZE facilitates subcutaneous injection delivery of biologics that are typically administered via infusion, providing additional treatment options to patients based on individual preferences.
“Every person living with gMG experiences the disease in their own way, including how they manage symptoms,” 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 and Principal Investigator for the ADAPT-SC trial. “For many years, patients lacked sufficient treatment options, let alone those that were tailored to their unique needs. These data, along with the recent approval of the intravenous formulation, VYVGART, represent exciting advancements in the management of this debilitating, unpredictable disease by offering patients and physicians the option to select treatment based on individual needs and preferences.”
“Our goal is to redefine and deliver targeted treatment options for people living with gMG globally. By listening to the gMG community, we heard the importance of creating optionality and flexibility for patients. The ADAPT-SC results mark another important step toward achieving this, and further support our vision of delivering a broad array of treatment options for gMG,” said Tim Van Hauwermeiren, Chief Executive Officer of argenx. “We’re excited about the potential to deliver two best-in-class options that provide flexibility around route of administration and dosing schedule, and look forward to collaborating with the FDA to bring another innovative treatment option to people living with gMG.”
Highlights of Topline ADAPT-SC Data
Primary endpoint of noninferiority was met (p< 0.0001); SC efgartigimod demonstrated mean total IgG reduction of 66.4% from baseline at day 29, compared to 62.2% with VYVGART. Results were consistent across the overall population, including those with acetylcholine receptor (AChR) antibodies and patients where AChR antibodies were not detected.
Additional key secondary endpoints were met, consistent with clinical efficacy results seen in the VYVGART Phase 3 ADAPT study, including:
69.1% of patients treated with SC efgartigimod were responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Responders are defined as having at least a two-point improvement on the MG-ADL score for at least four consecutive weeks.
65.5% of treated patients were responders on the Quantitative Myasthenia Gravis (QMG) score. Responders are defined as having at least a three-point improvement on the QMG score for at least four consecutive weeks.
Onset of effect and minimal symptom expression (defined as MG-ADL score of 0 or 1) were also consistent with ADAPT.
SC efgartigimod demonstrated a safety profile consistent with the Phase 3 ADAPT study. It was generally well-tolerated; the most frequent adverse event being injection site reactions (ISRs), commonly observed with biologics administered subcutaneously. All ISRs were mild to moderate and resolved over time.
Detailed data from the ADAPT-SC trial will be submitted for presentation at a future medical meeting.
Phase 3 ADAPT-SC Trial Design
The Phase 3 ADAPT-SC trial was a randomized, open-label, parallel-group, multicenter trial evaluating the noninferiority of the pharmacodynamic (PD) effect of SC efgartigimod (1000mg efgartigimod-PH20) as compared with IV efgartigimod (10mg/kg) in patients with gMG. The pharmacodynamic effect as measured by percent change from baseline in total IgG levels at day 29, one week after the last dose of IV or SC efgartigimod, served as the primary endpoint in the ADAPT-SC trial. The correlation between total IgG reduction and clinical benefit in gMG was demonstrated in a Phase 2 and the Phase 3 ADAPT trial, which served as the basis for approval of VYVGART in the U.S. and Japan. Safety, clinical efficacy, immunogenicity and pharmacokinetics (PK) were also assessed.
A total of 110 adult patients with gMG in North America, Europe and Japan enrolled in the ADAPT-SC trial and were treated. Inclusion criteria of the trial were the same as the Phase 3 ADAPT trial of VYVGART; enrolled patients had a confirmed gMG diagnosis and an 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 were on a stable dose of at least one gMG treatment prior to randomization, including acetylcholinesterase inhibitors, corticosteroids or nonsteroidal immunosuppressive drugs, and were required to remain on that stable dose throughout the primary trial.
Patients were randomized in a 1:1 ratio to receive SC efgartigimod or IV efgartigimod for one treatment cycle consisting of four doses at weekly intervals. The total study duration was approximately 12 weeks, including seven weeks of follow-up after the treatment cycle.