In adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), gefurulimab reduces MG-related hospitalizations and the need for rescue therapy, with a possible impact on reducing clinical deterioration, according to exploratory results from the phase 3 PREVAIL trial presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) annual meeting.
Gefurulimab is an investigational dual-binding nanobody that blocks complement component 5 activation and binds to albumin. Due to its low molecular weight and extended half-life, it can be administered subcutaneously weekly by self-injection.
The therapy was evaluated in the double-blind, placebo-controlled PREVAIL trial, which included 260 adults with AChR-Ab+ gMG, Myasthenia Gravis Foundation of America class II-IV disease, and a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score ≥5. The mean age at first treatment dose was 53 years, and most participants (60%) were women. The mean duration of MG was 9.2 years in the gefurulimab group and 8.2 years in the placebo group.
As reported previously, gefurulimab was well tolerated and provided early benefits versus placebo when it came to the change in MG-ADL score (primary endpoint) or quantitative myasthenia gravis (QMG) total score (secondary endpoint), with results maintained through the end of the 26-week randomized treatment period.
James Winkley, MD, a neurologist at Baptist Health Medical Group in Lexington, KY, reported an exploratory analysis examining several additional endpoints, including MG-related hospitalization, clinical deterioration, and the need for rescue therapy.
Rescue therapy with high-dose corticosteroids, plasmapheresis/plasma exchange, or IV immunoglobulin was permitted in life-threatening situations or in cases of clinical deterioration. Clinical deterioration was characterized by worsening signs or symptoms related to gMG associated with a significant increase in MG-ADL total score or by respiratory failure related to weakness of the respiratory or oropharyngeal muscles that either required intubation or delayed extubation.
The rate of protocol-defined clinical deterioration was lower with gefurulimab than with placebo, although the difference fell shy of statistical significance (6.9% vs 14.0%; odds ratio [OR] 0.445; 95% CI 0.191-1.038; P=0.0610). Most of these cases involved worsening signs or symptoms, with two patients (both in the placebo group) developing respiratory failure.
Use of rescue therapy was significantly less frequent in the gefurulimab group (5.3% vs 12.4%; OR 0.394; 95% CI 0.155-0.996; P=0.0491).
Regarding MG-related hospitalization, the most severe form of exacerbation, Dr. Winkley said, “I always find looking at these patients and the length of hospitalization a really complex measure. I think it's valid, but these patients also have lots of other comorbidities. What was their activity status before they went in? Do they have diabetes, COPD? How debilitated are those patients?”
Those issues notwithstanding, gefurulimab-treated patients were less likely to end up in the hospital than those who received placebo (2.3% vs 9.3%; OR 0.221; 95% CI 0.060-0.812; P=0.0229). The mean duration of hospitalization was about 15 days in both groups, although it varied widely—from 5 to 22 days in the gefurulimab group and from 4 to 30 days in the placebo group.
“These can be quickly resolved patients, but [hospitalization] can also be very prolonged,” Dr. Winkley said. “You can imagine a patient who has an ICU stay [and] needs plasma exchange potentially can be very slow to leave the hospitalization.”
