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MONTREAL — An open-label extension study of subcutaneous efgartigimod PH20 to treat chronic inflammatory demyelinating polyneuropathy (CIDP) showed durability of functional improvements to week 24, with no new safety signals.
As reported by Medscape Medical News, the US Food and Drug Administration (FDA) recently approved the coformulation of efgartigimod alfa and hyaluronidase-qvfc (VYVGART Hytrulo; Argenx) based on results of the pivotal phase 3 ADHERE study.
ADHERE+ was an open-label extension of that phase 3 trial, which was open to participants who completed the original trial and those who relapsed.
"Overall, 99% of patients that were eligible elected to go into the open-label extension, most of those patients stuck with the open-label extension until it closed…and overall adherence of receiving efgartigimod in the open-label extension was very high, almost 99%," reported principal investigator Jeffrey Allen, MD, associate professor at the University of Minnesota, Minneapolis.
The findings were presented on June 25 at the Peripheral Nerve Society (PNS) 2024 Annual Meeting.
First Novel, Precision Mechanism of Action in 30+ Years
CIDP is an autoimmune, inflammatory, demyelinating neuropathy, resulting in distal/proximal weakness and/or sensory deficits.
"Evidence supports a role for pathogenic IgG [immunoglobulin G] in the pathogenesis of CIDP, although in most patients, a specific antibody is currently not detectable," said Allen.
Efargartigimod, a once-weekly 30- to 90-second subcutaneous injection, is a neonatal Fc receptor (FcRn) blocker and the first novel, precision mechanism of action in > 30 years for the condition. By outcompeting endogenous IgG, it prevents recycling and promotes lysosomal degradation of IgG, leading to lower IgG levels, without impacting IgG production, Allen noted.
The ADHERE study involved several stages, including a run-in period, in which probable or definite CIDP patients had their diagnosis confirmed and all active treatment was withdrawn. Patients who deteriorated (n = 322) after treatment withdrawal were then given efgartigimod PH20 1000 mg once weekly for up to 12 weeks (Stage A), with responders then randomized to the same treatment (n = 111) or placebo (n = 110; Stage B).
Participants who completed the study (which ran until 88 patient relapses had been recorded), or who deteriorated, could then enter the ADHERE+ phase (n = 228).
The primary outcome was evidence of clinical improvement — assessed with the Inflammatory Neuropathy Cause and Treatment Disability Score, the inflammatory Rasch-built overall disability scale, or grip strength.
In Stage B, 27.9% of participants on efgartigimod PH20 relapsed compared with 53.6% of those on placebo (hazard ratio, 0.394; P = .00004), corresponding to a 61% lower risk for relapse in the treatment group.
In ADHERE+, patients who had relapsed in Stage B demonstrated clinical improvement, while those who had not relapsed in Stage B maintained these scores, Allen reported.
No New Safety Signals
There were no new safety signals in ADHERE+, with 57.7% of participants experiencing one or more mild to moderate treatment-emergent adverse events (TEAEs) and 9.2% having more serious TEAEs.
There were four deaths in the overall trial, two of them in Stage A, during which all participants were on study drug, one in Stage B in a patient on placebo, and one during the open-label extension, in a patient on efgartigimod PH20.
Only the death in the extension portion was considered to be a treatment-related death, said Allen, "although, at the time of death, that patient had been off efgartigimod for quite some time."
Efgartigimod can be self-administered or administered by a caregiver at home. Among study participants who took part in ADHERE+, 37% were successfully trained to self-administer the infusion, with an additional 6% of caregivers completing this training, added Allen.
Commenting on the findings for Medscape Medical News, Sara Austin, MD, a neurologist at Seton Brain and Spine Neurology and associate professor at Dell Medical School, University of Texas, Austin, Texas, said the neuromuscular community has looked forward to these results.
"It was impressive that 99% of eligible patients chose to continue in the ADHERE+ trial, pointing to tolerability and patient-perceived effectiveness," she said, noting that longer exposure to efgartigimod did not lead to increased treatment-emergent adverse events.
"CIDP is often a chronic, disabling disease. There is nothing that promises a cure, and although there are treatments, most involve significant expense in terms of both money and patient time," she said. "These results, along with FDA approval of efgartigimod, give clinical neurologists access to another treatment option."
The study was funded by Argenx. Allen disclosed relationships with Akcea therapeutics, Argenx SE, Alexion, Alnylym, Annexon, CSL Behring, Grifols, Immuovant, Immupharma, Johnson & Johnson, Pfizer, Takeda. Austin reported no relevant disclosures.
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