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PHOENIX -- The investigational agent riliprubart, a complement C1s inhibitor, showed encouraging activity in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), according to a phase II proof-of-concept study.

Among 25 patients who were responding to standard therapy, 88% maintained their response after switching to riliprubart, with nearly half also showing improvement in a variety of biomarkers, as measured by the 10-point Inflammatory Neuropathy Cause and Treatment (INCAT) score, reported Richard Lewis, MD, of Cedars-Sinai Medical Center in Los Angeles.

He told 番茄社区app that his team was "surprised by the outcomes of the patients who were responding to standard-of-care therapy, in that so many of them actually improved."

"We were trying to see if riliprubart would allow these patients to maintain their disease control, but what we found was that 44% of them actually showed improvement," he explained.

Furthermore, nine of 18 patients refractory to standard therapy responded to riliprubart, according to the poster presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine meeting.

These results exceeded historical placebo response rates (about 11%), the researchers pointed out in their poster.

Riliprubart, formerly known as SAR445088, is a humanized in the classical complement pathway. By inhibiting the pathway, the drug may block key inflammatory mechanisms underlying demyelination and axonal damage in CIDP.

Commenting on the study, Arindra Jayasekara, MD, of the University of California Riverside, told 番茄社区app that "CIDP often has a poor prognosis, so anything new other than intravenous immunoglobulin or plasma exchange -- which people don't tolerate that well because of side effects -- is promising."

However, he noted that the small number of patients in this study calls for larger studies to get a better sense of how the treatment would work in the clinic.

In this ongoing, three-tiered, 12-week trial, investigators included 25 patients who were being actively treated with standard-of-care therapy, including intravenous immunoglobulin, corticosteroids, immunosuppressants, rituximab (Rituxan), and other medications, who then discontinued these treatments and were started on subcutaneous riliprubart. Mean age was 58, and 80% were men. Median time since CIDP diagnosis was 7.9 years, and they reported CIDP symptoms for a median of 9 years.

A second group of 18 patients who had proven refractory to standard of care were also started on the investigational agent. Mean age was 63.9, and 61.1% were men. Median time since CIDP diagnosis was 4.5 years, and they had reported symptoms for a median of 5.6 years. They too had been on the same types of therapies before stopping them for futility.

A third group of 10 patients who were naive to any treatment for CIDP also received riliprubart, but these patients were not included in this report.

Patients in the refractory group had higher baseline scores on the INCAT, which measures ability to perform daily activities -- an average of 5.4, signifying serious impairment -- compared with an average of 3.3 among patients who were responding to standard of care.

At 12 weeks, the INCAT scores among the responders to standard of care decreased by an average of 1.91 points, and at 24 weeks, that reduction was 1.78 points. Reductions were a mean of 1.78 points at 12 weeks and 2.11 points at 24 weeks in the patients who were refractory to standard therapies.

Of the two groups, 65.1% reported at least one treatment-emergent adverse event (TEAE), and 7% reported serious TEAEs. The most common TEAEs (≥12% in each group) were headache, fatigue, COVID-19, nasopharyngitis, and injection site erythema. As for serious TEAEs, one patient refractory to standard of care had an infection with an encapsulated bacteria in the context of worsening CIDP and dysphagia, and two patients who responded to standard treatment had increases of alanine transaminase.

One patient in each of the two groups died during the trial, but the research team said those deaths were due to progressive comorbid disease, and were not believed to be associated with riliprubart.

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