Brainomix, a leading medtech company specializing in AI-powered imaging tools for stroke and lung disease, and Remedy Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing and bringing lifesaving treatments to people affected by stroke, have announced promising new findings from a post-hoc analysis of the Phase 3 CHARM trial (NCT02864953).
Presented this month at the World Stroke Conference in Seoul, the analysis explored the relationship between acute infarct core volume and the effect of intravenous glyburide (CIRARA) in patients with large hemispheric infarction (LHI). The results suggest Brainomix technology could help identify patients with severe stroke who may be more likely to benefit from treatment with CIRARA, an investigational therapy being developed by Remedy Pharmaceuticals.
“Patients with large hemispheric infarction face some of the most devastating outcomes in stroke and have very few treatment options, so it is exciting to see signals that a novel therapy such as CIRARA could offer them real benefit,” noted Dr George Harston, Chief Medical & Innovation Officer at Brainomix and Consultant Stroke Physician at Oxford University Hospitals.
Previous post-hoc analyses of the CHARM trial suggested a greater treatment effect in patients with smaller imaging-defined infarct cores, including those with CTP/MRI lesion volumes below 125 mL. Building on these findings, Brainomix used automated non-contrast CT (NCCT) analysis to measure acute infarct volume in 428 study patients, exploring whether this more widely available imaging method could help identify patients who may respond to treatment.
Using Brainomix 360 Stroke software and research functionality from its in-house AI Core Lab, Brainomix analyzed baseline and follow-up NCCT, CTP and DWI-MRI scans alongside clinical outcomes. In the per-protocol analysis of 362 patients, excluding patients enrolled using NCCT with an e-ASPECTS score above 5, CIRARA showed a borderline association with improved functional outcomes on the modified Rankin Scale (mRS).
In a subgroup of 191 patients with an acute infarct core volume below 125 mL, CIRARA was significantly associated with improved outcomes, including a favorable mRS shift and a greater likelihood of achieving mRS 0–3 at 90 days. A broader modified intention-to-treat analysis of 428 patients also found a significant non-linear interaction between acute infarct core volume and treatment allocation for improved outcomes, suggesting that both lower and upper infarct-volume thresholds may influence treatment response.
Sven Jacobson, CEO of Remedy Pharmaceuticals, said: “We are excited by the additional signals of efficacy for CIRARA emerging from this analysis of the CHARM dataset. Seeing CIRARA associated with significantly improved functional outcomes in patients with imaging characteristics defined on non-contrast CT (NCCT) supports the potential for the selection of treatable patients using NCCT. The insights from the Brainomix analysis are encouraging and we look forward to investigating these findings further. We are committed to advancing the CIRARA program in patients with large hemispheric infarction, a devastating form of stroke with very limited treatment options.”
Dr George Harston added: “This analysis suggests that the patients most likely to respond to CIRARA could be identified using automated analysis of non-contrast CT, the most widely available form of stroke imaging. Removing the need for advanced imaging opens up the opportunity to select patients for clinical trials at far more hospitals,widening access to trial participation and, ultimately, to treatment. Robust, reproducible imaging analysis will be essential to ensure that promising novel therapies are successfully translated from clinical trials into routine clinical practice, so that they reach the patients who need them most.”
These exploratory findings support further evaluation of CIRARA in selected patients with LHI. They also highlight the potential of automated imaging biomarkers, including those derived from widely available NCCT, to inform patient selection and the design of future stroke trials.
About the CHARM Phase III Study
Insights from the Phase 3 CHARM Trial
The CHARM clinical trial was a double-blind, randomized, placebo-controlled Phase 3 study evaluating CIRARA in patients aged 18–85 with LHI. The trial enrolled 535 patients, including an efficacy analysis population of 431 patients aged 18–70. Treatment was initiated within 10 hours of symptom onset. The study, sponsored by Biogen,was terminated prematurely following a strategic realignment of resources, and the programme has since been returned to Remedy Pharmaceuticals. CIRARA is an investigational product and has not been approved by any regulatory authority.
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