Global trial validates self-administered treatment for myasthenia gravis
On doctor and patient scales, injection therapy shows effectiveness in gMG
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- In a global trial, a self-administered injection therapy for generalized myasthenia gravis was shown to be both safe and effective, meeting its main goal.
- Called PREVAIL, the trial tested gefurulimab in more than 250 people with gMG who have anti-AChR antibodies.
- The final data suggest gefurulimab may be a convenient and long-lasting treatment for easing gMG symptoms.
In a global late-stage trial testing gefurulimab for generalized myasthenia gravis (gMG), the injection treatment candidate was shown to safely and effectively ease gMG symptoms — per both patient-reported and physician-rated scales.
That’s according to the final results from this Phase 3 clinical trial, called PREVAIL (NCT05556096), in which participants self-administered the experimental therapy via under-the-skin (subcutaneous) injections once weekly. The trial, conducted at 132 locations across four continents, involved more than 250 people with the autoimmune neuromuscular disorder.
Alexion, AstraZeneca Rare Disease is developing gefurulimab as a treatment for individuals with gMG who have antibodies against the acetylcholine receptor (AChR) protein, the most common target of disease-driving antibodies.
PREVAIL’s results were described in a study titled “Efficacy and Safety of Gefurulimab in Generalized Myasthenia Gravis: The PREVAIL Phase 3 Randomized Clinical Trial,” which was published in the journal JAMA Neurology. Several authors are employees of Alexion, which funded the trial.
“Compared with the available therapies for gMG, the administration route and dosing regimen of gefurulimab may provide patients a convenient treatment option with predictable treatment schedule and greater autonomy,” the researchers wrote.
In gMG, the immune system produces antibodies that mistakenly target proteins that facilitate communication between nerves and muscles, most commonly AChR. This leads to symptoms of muscle weakness across the body.
Researchers believe that a part of the immune system called the complement system contributes to gMG, specifically when anti-AChR antibodies are present. For this reason, several approved treatment options for this type of gMG aim to reduce activity in the complement system.
Three such therapies target a complement protein called C5: Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), and Zilbrysq (zilucoplan). Soliris and Ultomiris, both marketed by Alexion, require intravenous, or into-the-vein, infusions under medical supervision. Zilbrysq, marketed by UCB, is given by daily subcutaneous injections that can be self-administered.
Gefurulimab designed for at-home use, but less frequent dosing
Alexion designed gefurulimab to offer the convenience of Zilbrysq’s at-home dosing with a less frequent dosing schedule. It is based on a nanobody, a type of very small antibody derived from camel blood. The nanobody’s size makes it appropriate for a subcutaneous injection.
In addition to C5, the nanobody binds to albumin, a naturally occurring protein that lasts a long time in the blood. This helps gefurulimab stay in the body for longer, allowing for weekly dosing.
“Collectively, these design features render gefurulimab a convenient treatment option offering patients more autonomy and greater flexibility compared with currently available therapies,” the researchers wrote.
The global PREVAIL study tested gefurulimab versus a placebo in 260 adults with anti-AChR antibody-positive gMG. The participants’ average age at diagnosis was 44.2, and 52.8 at the start of the trial. For 26 weeks, or about six months, the participants self-administered subcutaneous weekly injections of their assigned agent.
As previously announced by Alexion, data showed that the therapy was superior to the placebo at significantly reducing disease severity after 26 weeks.
This was assessed with the MG Activities of Daily Living (MG-ADL) questionnaire, which measures how symptoms affect everyday life — the study’s main outcome — and the Quantitative MG (QMG) scale, which evaluates muscle weakness, a key secondary outcome. In both measures, higher scores indicate more severe disease.
gMG treatment for anti-AChR antibodies meets trial’s main goal
The final published data show that a significant difference in MG-ADL scores between the placebo and gefurulimab groups emerged as soon as one week after starting treatment.
By the end of the trial, the gefurulimab group had a mean 4.2-point decrease in MG-ADL scores, surpassing the three-point reduction threshold considered to be clinically meaningful. This score drop was significantly larger than the 2.6-point reduction seen in the placebo group, the researchers noted.
QMG score reductions with gefurulimab were observed as early as week 4 — the first assessment after treatment was started — and were sustained for six months. At week 26, the therapy was associated with a significantly greater drop in QMG scores relative to the placebo (4.5 vs. 2.4), the data showed.
Additionally, a significantly greater proportion of gefurulimab-treated participants achieved predefined criteria for a response to treatment based on the MG-ADL (65.6% vs. 52.1%) and QMG scores (46.8% vs. 28%). These results met two other secondary goals of the trial.
“The significant difference in the responder rates between the gefurulimab and placebo groups underscores the robust symptom reduction achieved with gefurulimab,” the researchers wrote.
Gefurulimab demonstrated both early and sustained clinical benefit in [anti-AChR antibody-positive] gMG and was well tolerated, supporting its potential as a convenient, once-weekly, self-administered treatment regimen.
Rates of adverse events were comparable between the gefurulimab and placebo groups (76% vs. 81%), and these events were largely mild or moderate in severity. In the gefurulimab group, the most commonly reported adverse events were headache, affecting about 10% of participants, back pain, experienced by about 8%, and the common cold, seen for about 7%.
Reactions at the injection site affected more individuals in the gefurulimab group than the placebo group (10% vs. 3%). Still, most injection site reactions occurred early in the trial and eased with subsequent injections. No participants withdrew from the study due to these reactions.
Overall, “gefurulimab demonstrated both early and sustained clinical benefit in [anti-AChR antibody-positive] gMG and was well tolerated, supporting its potential as a convenient, once-weekly, self-administered treatment regimen,” the team wrote.
Participants completing PREVAIL’s six-month, placebo-controlled portion could enter its open-label extension portion, in which all are receiving gefurulimab for up to 202 weeks, or nearly four years. The extension is designed to assess the therapy’s long-term effects.
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