Nancy A. Melville
PHOENIX — Subcutaneous efgartigimod PH20 SC shows efficacy and tolerability in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), providing a convenient alternative to intravenous and other older treatments for this rare disease.
“This was the largest study of CIDP that has been performed, with over 600 patients screened and 322 enrolled, and was the first to use an adjudication committee to confirm the diagnosis,” study investigator Richard Lewis, MD, of the Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, told Medscape Medical News.
Furthermore, “this is the first new treatment for CIDP in over 30 years, so it’s very exciting. It is a brief subcutaneous injection which should be something that patients will appreciate,” he said.
The study (abstract P143) was presented on November 2 at the 2023 American Association of Neuromuscular Electrodiagnostic Medicine (AANEM) Annual Meeting.
Filling an Unmet Need
A rare and often debilitating autoimmune disorder, CIDP is characterized by weakness and numbness that can result in disability, pain, and fatigue and has been linked to immunoglobulin (Ig)–G autoantibodies.
Treatments include corticosteroids, intravenous Ig (IVIg), subcutaneous Ig, and plasma exchange, but not all patients achieve meaningful benefits and factors including safety risks, costs, and burdensome treatment regimens.
“There is an unmet need for a first-line treatment with long-term efficacy that maintains or improves quality of life, has an early onset of action, is well tolerated, is not dependent on plasma donation, and has greater convenience,” the investigators write in their abstract.
Efgartigimod, which is approved in its IV and subcutaneous forms for the treatment of myasthenia gravis, is a human IgG1–antibody Fc receptor blocker designed to reduce pathogenic IgG autoantibody levels, which may be drivers of pathogenesis in CIDP.
The therapy is a coformulation of efgartigimod and recombinant human hyaluronidase that allows for rapid subcutaneous administration of larger volumes and is administered as a 90-second subcutaneous injection once weekly.
For the ongoing phase 2 ADHERE trial, 322 patients with a diagnosis of CIDP and active disease who were either treatment-naive or receiving standard treatments were withdrawn from their treatments prior to day 1 of a run-in period of up to 12 weeks.
They then entered stage A of the study, an open-label phase in which all were treated with 1000-mg efgartigimod PH20 SC weekly for up to 12 weeks.
Of those patients, 66% showed evidence of clinical improvement and a rapid onset of effect with the efgartigimod PH20 SC treatment, and 70% of the patients were then entered into stage B, a double-blind randomized phase, with 111 of patients receiving continued efgartigimod PH20 SC weekly and 110 receiving placebo for 48 weeks.
Of those moving on to stage B, more than 70% were on IVIg prior to the time of enrollment.
The study met its primary endpoint, with the efgartigimod PH20 SC groups showing a 61% lower risk for relapse on the basis of time to a first adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) deterioration compared with placebo (hazard ratio, 0.39; P = .000039).
Clinical benefits were also observed on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) and in measures of mean grip strength in all groups regardless of prior CIDP medication.
Specifically, efgartigimod patients had a mean improvement of 7.7 points on I-RODS and 12.3 kPa on mean grip strength in stage A, which was maintained in stage B. These were partially lost in patients receiving placebo.
In terms of safety, most adverse events were mild or moderate in severity, and no new safety signals were identified with up to 60 weeks of treatment. There were no increased infection rates with increased exposure.
The findings show that “efgartigimod-PH20, given as a 90-second subcutaneous injection once a week, was effective in treating patients with CIDP who had relapsed when taken off their previous treatment (IVIg or corticosteroids),” said Lewis.
“[The study] then showed that the majority of patients, over 70%, maintained that improvement compared to placebo, where over 50% relapsed — most within 8 weeks, so the treatment, which reduces circulating immunoglobulin G by over 70%, is effective in treating CIDP,” he added.
Plans for this ongoing trial include recruiting up to 360 patients until 88 events of clinical deterioration have been observed in stage B.
Promising Data
Commenting on the study for Medscape Medical News, Karissa Gable, MD, an associate professor of neurology at Duke University School of Medicine, in Durham, North Carolina, said that the “initial data reported from the ADHERE study is very promising and demonstrated significant efficacy.”
The study’s use of an adjudication committee in confirming the diagnosis is particularly notable, she said.
“The trial design demonstrated confirmation of diagnosis and activity of disease and response to drug prior to randomization, which is a novel design that is particularly applicable to patients with CIDP given the rate of misdiagnosis and placebo effect found in other trials.”
Gable agreed that new options are important to address an unmet need in CIDP.
“The current first-line treatments are generally 80-90% effective, however, there are limited options with respect to the first line treatments due to side effects and comorbid disease in patients,” she explained.
“Other treatments options are needed and so this is an unmet need in patients with CIDP,” Gable said. “This medication will be likely to be one that will provide a strong alternate option for treatment.”
Overall, “this is a novel mechanism for drug treatment for CIDP and seems to demonstrate efficacy and good safety and tolerability based on the initial report of the data,” Gable added.
“It will likely be a promising medication to use for these patients to fill the unmet need for treatment of patients with CIDP.”
The study was sponsored by Argenx. Lewis disclosed relationships with Argenx and other companies involved in neuromuscular disease therapies. Gable is on the global medical advisory board steering committee for Argenx and she was the PI at her site for the Adhere study. Gable has served as a consultant for Immunovant and Takeda as well as Sanofi for CIDP and she is on the Takeda speaker bureau for Huyquvia for treatment of CIDP.
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