Conference Coverage

First new treatment in 30 years for rare disease is effective, tolerable, convenient



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,” said study investigator Richard Lewis, MD, of the department of neurology, Cedars-Sinai Medical Center, Los Angeles.

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 was presented at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

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 IgG autoantibodies.

Treatments include corticosteroids, intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin, and plasma exchange, but not all patients achieve meaningful benefits and many patients complain about 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 wrote in their abstract.

Efgartigimod, which is approved in its intravenous 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with a diagnosis of CIDP and active disease who were either treatment naive or receiving standard treatments were withdrawn from their treatments prior to day 1 of a run-in period of up to 12 weeks.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 1,000-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 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 Dr. Lewis.

“[The study] then showed that the majority of patients, over 70%, maintained that improvement, compared with 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.


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