Ocular Myasthenia Gravis Scores Improve With Subcutaneous Treatment

Subcutaneous efgartigimod PH20 (Vyvgart Hytrulo) met the primary endpoint in the phase III ADAPT OCULUS trial of people with ocular myasthenia gravis show, interim data showed.

At 4 weeks, ocular myasthenia gravis patients treated with efgartigimod PH20 had a significant improvement from baseline in Myasthenia Impairment Index (MGII) Patient Reported Outcome (PRO) ocular scores compared with those who received placebo, reported Vern Juel, MD, of Duke University School of Medicine in Durham, North Carolina, at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) meeting in Orlando.

Mean change from baseline in the efgartigimod-treated group was a 4.04-point improvement in MGII PRO score versus a change of 1.99 points in patients treated with placebo (mean difference 2.05 points, P=0.012), Juel said.

On a key secondary outcome — MGII PRO plus physician examination (MGII PRO+PE) scores — the mean change from baseline was 5.02 points with efgartigimod and 2.57 points with placebo, a difference of 2.44 points (P=0.018).

Myasthenia Gravis Activities of Daily Living (MG-ADL) ocular domain scores, another key secondary outcome, followed a similar numerical trend, but the difference between the treatment and the placebo groups was not significant (P=0.60).

Efgartigimod significantly improved diplopia (double vision) and ptosis (eyelid drooping) in patients with ocular myasthenia gravis, Juel said.

Despite not reaching statistical significance, the MG-ADL ocular domain score improvements were consistent with the primary MGII PRO ocular endpoint, supporting the use of MGII PROs for detecting treatment effects in ocular myasthenia gravis, he added.

“The patient-reported symptoms are key and paramount to testing the effectiveness of a drug,” observed Jeff Guptill, MD, of drugmaker argenx and Duke University, at the AANEM’s Myasthenia Gravis Foundation Association (MGFA) scientific session.

“We know that the seminal findings of ocular myasthenia gravis relate to diplopia and ptosis, but we also need to measure that impact effectively with an outcome measure,” Guptill said. “And we know … with emerging data, that ocular myasthenia gravis extends just beyond the immediate symptoms that we see at the bedside related to vision and can impact in other areas, including problems with usual activities, and anxiety, and depression.”

The MGII PRO scale can be broken down into two sections, a generalized score and an ocular score, “and we were focused for this particular trial on the overall ocular score,” Guptill explained. Scores for the patient-reported symptoms can range from 0 to 18 and scores on the physical exam items can range from 0 to 5 for a total score of up to 23, with higher scores representing more severe disease, he said.

Ocular myasthenia gravis has been understudied historically and there’s an unmet need for safe, effective, and targeted therapies, Juel noted. Retrospective analyses of efgartigimod studies in generalized myasthenia gravis have indicated an improvement in ocular symptoms, he said.

Efgartigimod is a human immunoglobulin G1 (IgG1) antibody fragment that binds to the neonatal Fc receptor (FcRn), leading to a reduction in circulating IgG autoantibodies. In 2021, efgartigimod was approved as an IV treatment to treat generalized myasthenia gravis patients with anti-acetylcholine receptor (AChR) antibodies. In 2023, the FDA approved a subcutaneous formulation with hyaluronidase (efgartigimod PH20). Efgartigimod also is approved to treat chronic inflammatory demyelinating polyneuropathy.

In 2026, the FDA expanded efgartigimod’s indication to treat all people with generalized myasthenia gravis, including those with anti-muscle-specific tyrosine kinase (MuSK) antibodies, with anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibodies, or without detectable autoantibodies against AChR, MuSK, or LRP4 (triple seronegative).

The ADAPT OCULUS trial assessed the efficacy and safety of efgartigimod PH20 in 141 patients with ocular myasthenia gravis. Participants had myasthenia gravis of any serotype, MGFA class I disease and an MGII PRO ocular score of at least 6. At study entry, they were on a stable dose of acetylcholinesterase inhibitors, corticosteroids, or non-steroid immunosuppressive therapies, either alone or combined.

The 71 participants randomized to the efgartigimod group had a mean baseline age of 54 and 31% were women. Most (81.3%) had anti-AChR antibodies and 16.9% were triple seronegative.

In part A, participants received four once-weekly injections of either 1,000 mg of efgartigimod or placebo, followed by a 4-week follow-up period. In the part B open-label extension, participants received multiple cycles of efgartigimod treatment.

The primary outcome was the MGII PRO ocular score change from baseline to week 4 in part A. Across treatment cycles, MGII PRO ocular scores improved in both the anti-AChR and triple seronegative populations, Juel noted.

Adverse events were consistent with prior clinical studies and real-world evidence in people with general myasthenia gravis, he added.

There was one serious treatment-emergent adverse event in part A of the trial and 17 events in parts A and B combined. In both parts of the trial, headache, injection site erythema, and upper respiratory tract infections were the most common treatment-emergent adverse events.

Efgartigimod is not currently approved by the FDA for ocular myasthenia gravis. ADAPT-OCULUS is the first registrational study to specifically evaluate a targeted treatment for ocular myasthenia gravis, drugmaker argenx said.