New data from a post-hoc analysis of the Phase 3 CHARM trial suggests that intravenous glibenclamide (CIRARA; Remedy Pharmaceuticals) significantly improves the ability to ambulate independently in patients with large hemispheric infarction (LHI), particularly when used with endovascular thrombectomy (EVT).
Improved Functional Outcomes with Glibenclamide
The CHARM trial, a multicenter, multinational, double-blind, randomized, placebo-controlled study, involved 535 patients aged 18-85 with LHI. While the trial was terminated early by Biogen due to strategic realignment, post-hoc analyses revealed encouraging results. Specifically, patients with lesion volumes under 125 mL (n = 118) treated with CIRARA reported an odds ratio (OR) of 4.1 to achieve modified Rankin Scale (mRS) scores of 0-3 (P < .01).
Sven Jacobson, CEO of Remedy Pharmaceuticals, stated, "These new findings are incredibly encouraging and provide strong evidence that CIRARA could be a game-changer in the treatment of large hemispheric infarction." He highlighted the potential of CIRARA to revolutionize stroke care and offer new hope to patients and their families, citing significant improvements in functional outcomes and increased rates of independent ambulation.
Synergistic Effect with Endovascular Thrombectomy
In a modified intent-to-treat population with a lesion volume of less than 125 mL (n = 34) who received CIRARA with EVT, researchers reported an OR of 18.5 to achieve a better functional outcome, particularly in the ability to ambulate independently (P = .03). This suggests a synergistic effect between CIRARA and EVT in improving patient outcomes.
Data showed that 78% of EVT patients treated with CIRARA were able to walk independently at 12 months, compared to only 51% in the placebo group – a 55% relative increase.
Impact on Modified Rankin Scale (mRS)
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. An mRS score of 0-3 indicates moderate disability or better, including the ability to ambulate independently.
Among those in the mITT population with computed tomography perfusion (CTP)/MRI lesion volume less than 125 mL (n = 118), results showed an OR of 2.15 in favor of CIRARA (P = .04) for ambulating independently. The proportion of patients with an mRS between 0-3 was 36% in the CIRARA group vs 19% for those on placebo, representing an 89% increase.
Previous Promising Data
Previous data from the CHARM trial announced in May 2024 showed that treatment with CIRARA resulted in meaningful improvements in functional outcomes among subgroups of patients with LHI. In a subgroup of patients with National Institute of Health Stroke Scale (NIHSS) less than 20 (n = 274), findings showed statistically significant improvements in functional outcomes on the mRS, indicated by OR of 1.66 (P = .03). With EVT therapy increasingly used in LHI, investigators observed an OR of 1.75 favoring CIRARA in combination with the treatment.
The Need for New Treatments
Currently, there are no medications available to specifically reduce brain swelling caused by LHI. Kevin Sheth, MD, a professor of neurology and director of the Yale Center for Brain & Mind Health, and co-principal investigator on the CHARM study, noted that mortality and long-term disability remain stubbornly high, especially in cases of severe stroke. He suggested that CIRARA could help the tens of thousands of patients who fall victim to LHI each year have a fighting chance to live and enjoy productive lives.
Future Directions
Remedy Pharmaceuticals is planning a confirmatory Phase 3 study of CIRARA in LHI, encouraged by these latest findings. The company believes that CIRARA has the potential to dramatically improve outcomes for patients suffering from severe ischemic stroke.
