New Phase 3 study results support Vyvgart Hytrulo in ocular MG
ADAPT OCULUS met its primary endpoint after four weeks
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Four weekly under-the-skin injections of Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) led to a marked reduction in double vision and drooping eyelids in adults with ocular myasthenia gravis (MG), according to top-line Phase 3 results.
These findings come from the global Phase 3 ADAPT OCULUS clinical trial (NCT06558279), which is evaluating the therapy — already approved for generalized MG — in 141 adults whose symptoms were limited to the eyes.
Because the trial met its primary outcome — showing a statistically significant improvement compared with placebo after four weeks — the drug’s developer, Argenx, said it plans to apply to the U.S. Food and Drug Administration (FDA) to expand the therapy’s approval to include ocular MG.
Phase 3 trial targets unmet need in ocular MG
“ADAPT OCULUS is the first registrational study specifically designed to evaluate a targeted therapy for ocular myasthenia gravis,” Luc Truyen, MD, PhD, chief medical officer of Argenx, said in a company press release. Registrational studies are designed to generate the safety and efficacy data needed to support regulatory approval.
“These positive results deliver on our patient-centered approach to drug development and bring us one step closer to our vision of delivering a targeted, transformative treatment option to as many MG patients as possible and ensuring no patient is left behind,” Truyen said.
Full trial data are expected to be presented at a future medical meeting.
In MG, the immune system mistakenly produces self-targeted antibodies that attack proteins on muscle cells needed to receive nerve signals. This disrupts communication between nerves and muscles, leading to symptoms such as muscle weakness and fatigue.
In many cases, weakness first affects the muscles that control eye movement and eyelids, a form known as ocular MG, causing double vision and drooping eyelids. Up to 60% of people with ocular MG later develop generalized MG, in which weakness spreads to other parts of the body, including the arms, legs, jaw, throat, or breathing muscles.
“Ocular myasthenia gravis significantly impacts patients’ daily lives, affecting vision, independence and the ability to do routine tasks, such as work or drive a car,” said Carolina Barnett-Tapia, MD, PhD, associate professor of medicine at the University of Toronto, in Canada. “Yet today, there are no approved targeted medicines for this disease.”
Truyen added: “Ocular MG has been historically under-studied and represents a significant unmet need in the MG community.”
How Vyvgart Hytrulo works in myasthenia gravis
Vyvgart Hytrulo, marketed as Vyvgart SC in Europe and Vyvdura in Japan, works by blocking FcRn, a receptor protein that helps antibodies stay in the bloodstream longer. By blocking FcRn, the therapy lowers overall antibody levels, including antibodies believed to drive MG symptoms.
The therapy is a newer version of Vyvgart (efgartigimod alfa-fcab), which is approved for adults with generalized MG who test positive for self-targeted antibodies against the acetylcholine receptor (AChR), the most common MG-related antibody.
Vyvgart Hytrulo is approved for the same indication as Vyvgart, but instead of being given as an intravenous infusion lasting about an hour, it is delivered through quick under-the-skin (subcutaneous) injections.
Single-dose, ready-to-use syringes of Vyvgart Hytrulo became available in the U.S. last year for use in generalized MG. Here, injections last about 30 seconds and can be given by a caregiver or patient with appropriate training.
With the goal of expanding Vyvgart Hytrulo’s use to ocular MG, Argenx launched ADAPT OCULUS to test the therapy against a placebo in adults whose MG-related weakness was limited to the eye muscles. Participants included both those who tested positive for anti-AChR antibodies and those diagnosed based on clinical and neurophysiological testing.
A total of 141 participants were enrolled at more than 100 sites worldwide. Before entering the study, participants were on stable MG treatments, such as acetylcholinesterase inhibitors, corticosteroids, or nonsteroidal immunosuppressive drugs.
How the ADAPT OCULUS trial was designed
In the trial’s first part, participants were randomly assigned to receive four once-weekly injections of Vyvgart Hytrulo or a placebo, given using prefilled syringes.
The main goal was to measure changes in ocular MG symptom severity after four weeks using the patient-reported Myasthenia Gravis Impairment Index (MGII) ocular score, in which higher scores reflect more severe symptoms.
After four weeks, participants receiving Vyvgart Hytrulo had a 4.04-point average reduction in MGII ocular scores, compared with a 1.99-point reduction among those receiving placebo. Treated participants also experienced reductions in double vision and drooping eyelids.
Vyvgart Hytrulo was generally well tolerated, with a safety profile consistent with earlier studies in generalized MG. No new safety concerns were reported.
Participants who completed the placebo-controlled portion may enroll in the second part of the study, where all will receive Vyvgart Hytrulo in two treatment cycles of four weekly injections separated by four weeks. Additional cycles may begin at least one week after the previous cycle, depending on clinical need.
“The improvements observed with Vyvgart in the OCULUS trial offer hope to the thousands of myasthenia gravis patients with ocular involvement,” Barnett-Tapia said.
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