Remedy Pharmaceuticals recently announced promising new data from the Phase 3 CHARM clinical trial of Cirara (intravenous glyburide) in patients with large hemispheric infarction (LHI)—a serious form of ischaemic stroke characterised by large volume lesions that can lead to malignant brain swelling, severe disability, and death.
The analysis revealed significant and clinically meaningful improvements in patients’ ability to ambulate independently following administration of Cirara, particularly when used in combination with endovascular therapy (EVT), according to a company press release.
The CHARM clinical trial was a multicentre, multinational, double-blind, randomised, placebo-controlled Phase 3 study involving patients aged 18–85 years with LHI. Patients were eligible if the study drug was expected to start within 10 hours after they were last known well. A total of 535 patients were enrolled, including 431 patients aged 18–70 years—the efficacy analysis population—and 81 patients aged 71–85 years.
The study was terminated early by Biogen after a strategic realignment of resources, leading to the return of the programme to Remedy, the latter company’s recent release notes.
In May 2024, Remedy conducted prespecified subgroup analyses, along with post-hoc analyses examining the impact of lesion volume on outcomes, which revealed significant improvements in functional outcomes on the modified Rankin scale (mRS) at 90 days. Specifically, in the prespecified modified intention-to-treat (mITT) population with National Institutes of Health stroke scale (NIHSS) scores ≤20—consisting of 274 patients—Cirara improved outcomes with an odds ratio (OR) of 1.8 (p=0.01).
In a post-hoc analysis of 118 patients with computed tomography perfusion (CTP)/magnetic resonance imaging (MRI) lesion volume <125mL, the OR for improved 90-day outcome was 2.2 in favour of Cirara versus placebo (p=0.04). Additionally, in the EVT population of 34 patients with CTP/MRI lesion volume <125mL, the OR was 7.1 in favour of the drug (p=0.01).
Remedy’s recent release states that further post-hoc analyses have now been performed and show that the OR for achieving an mRS score of 0–3, meaning moderate disability or better, in the 118 patients with a lesion volume <125mL was 4.1 in favour of Cirara (p<0.01). The release also highlights the fact that an mRS of 0–3 includes the ability to ambulate independently—a “highly desirable outcome”.
In the mITT EVT population with a lesion volume <125mL, consisting of 34 patients, the OR for achieving an mRS score of 0–3 was 18.5 in favour of Cirara (p=0.03), indicating an even more dramatic improvement in functional outcomes, particularly in the ability to ambulate independently, Remedy further claims.
“These new findings are incredibly encouraging and provide strong evidence that Cirara could be a gamechanger in the treatment of LHI,” said Sven Jacobson, chief executive officer of Remedy. “The significant improvements in functional outcomes, and particularly the increased rates of independent ambulation, highlight the potential of Cirara to revolutionise stroke care, and offer new hope to patients and their families.”
