Brainomix and Remedy Pharmaceuticals have announced “promising new findings” from a post-hoc analysis of the Phase 3 CHARM trial. Presented at last week’s World Stroke Congress (WSC; 21–23 October, Seoul, South Korea), the analysis explored the relationship between acute infarct core volume and the effect of intravenous glyburide (Cirara) in patients with large hemispheric infarction (LHI), with results suggesting Brainomix’s 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.
“Patients with LHI 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 George Harston (Oxford University Hospitals, Oxford, UK), chief medical and innovation officer at Brainomix.
Previous post-hoc analyses of the CHARM trial have indicated a greater treatment effect in patients with smaller imaging-defined infarct cores, including those with computed tomography perfusion (CTP)/magnetic resonance imaging (MRI) lesion volumes below 125mL. 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 artificial intelligence (AI) core lab, the company analysed baseline and follow-up NCCT, CTP and diffusion-weighted imaging (DWI)-MRI scans alongside clinical outcomes. In the per-protocol analysis of 362 patients—excluding patients enrolled using NCCT with an e-Alberta stroke programme early CT score (e-ASPECTS) of more than 5—Cirara showed a borderline association with improved functional outcomes on the modified Rankin scale (mRS).
Additionally, in a subgroup of 191 patients with an acute infarct core volume below 125mL, Cirara was significantly associated with improved outcomes, including a favourable 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.
“We are excited by the additional signals of efficacy for Cirara emerging from this analysis of the CHARM dataset,” said Remedy chief executive officer (CEO) Sven Jacobson. “Seeing Cirara associated with significantly improved functional outcomes in patients with imaging characteristics defined on 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.”
“This analysis suggests that the patients most likely to respond to Cirara could be identified using automated analysis of NCCT, the most widely available form of stroke imaging,” Harston added. “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, and 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, Brainomix claims.
CHARM was a double-blind, randomised, placebo-controlled Phase 3 study evaluating Cirara in patients aged 18–85 years with LHI. The trial enrolled 535 patients, including an efficacy analysis population of 431 patients aged 18–70 years. 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.
Cirara remains an investigational product that has not been approved by any regulatory authority.
