Remedy Pharmaceuticals Gets Rights To Acute Stroke Drug Back From Biogen; Announces Clinically Meaningful and Statistically Significant Results From Pre-specified Subgroup and Post Hoc Analyses of Phase 3 Study

New York – May 29, 2024 – Remedy Pharmaceuticals, a pioneer in stroke drug development, announced that prespecified subgroup analyses from the Phase 3 CHARM clinical trial of CIRARA (IV glibenclamide) showed meaningful improvements in functional outcomes on the modified Rankin Scale (mRS), which were further validated in post hoc analyses.

The findings follow the early termination of the pivotal Phase 3 trial by Cambridge-based Biogen after a strategic realignment of resources, and the return of the program to Remedy.

The CHARM clinical trial was a multicenter, multinational, double-blind, randomized, placebo-controlled Phase 3 study involving patients aged 18-85 with a large hemispheric infarction (LHI), as indicated by an Alberta Stroke Program Early Computed Tomographic (CT) Score (ASPECTS) value of 1-5 (on a scale of 0-10) or an ischemic core volume of 80-300 ml by CT perfusion (CTP) or magnetic resonance imaging (MRI) diffusion weighted imaging. Patients were eligible if study drug was expected to start within 10 hours after they were last known well and were randomly assigned in a 1:1 ratio of CIRARA or placebo. A total of 535 patients were enrolled, including 431 patients aged 18-70 (the efficacy analysis population) and 81 patients aged 71-85.

Despite neutral top-line results, in pre-specified analyses, patients who received rtPA, underwent endovascular thrombectomy (EVT), were enrolled using CTP/MRI, had wake-up strokes, or were enrolled in the U.S., all had directionally improved functional outcomes in favor of CIRARA.  A pre-specified analysis in patients with an NIH Stroke Scale (NIHSS) ≤20 (n=274) yielded statistically significant improvements in functional outcomes (Odds Ratio 1.66, p=0.03). With EVT therapy increasingly used in LHI, the Odds Ratio of 1.75 in the EVT subset, while not statistically significant, was particularly encouraging.  

Building on these findings, post hoc analyses examining the impact of stroke severity on outcomes were performed and revealed significant findings:

  • In the mITT population with CTP/MRI lesion volume <125mL (n=118), the Odds Ratio = 2.15 in favor of CIRARA (p=0.04). Mortality was numerically decreased from 22% in the placebo to 14% in the CIRARA group without an increase in severe disability. The proportion of patients with a mRS 0-3 was 36% for the CIRARA group vs.19% for placebo, an 89% increase.
  • In the mITT EVT population with CTP/MRI lesion volume <125mL (n=34), the Odds Ratio = 7.13 in favor of CIRARA (p=0.01). Mortality was numerically decreased from 31% in the placebo to 6% in the CIRARA group without an increase in severe disability. The proportion of patients with mRS 0-3 was 62% for the CIRARA group vs. 31% for placebo, a 100% increase.

Dr. W. Taylor Kimberly, MD, PhD., Chief, Division of Neurocritical Care at Massachusetts General Hospital, Associate Professor of Neurology at Harvard Medical School and co-principal investigator on the CHARM study, commented, “These findings are very promising and suggest that CIRARA is complementary to current standard of care, such as tPA and endovascular therapy, and could be the next big advancement in the treatment of large hemispheric infarctions.”

“Mortality and long-term disability remain stubbornly high, especially in cases of severe stroke,” notes Kevin Sheth, MD, Professor of Neurology and Neurosurgery and a Director of the Yale Center for Brain & Mind Health, and co-principal investigator on the CHARM study. “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.”

“Advancing medicine cannot happen without the truly inspiring dedication of participants, their families, and the clinical investigators around the world,” said Sven Jacobson CEO of Remedy. “We thank Biogen for investing over $200 million in this program, and express our gratitude to all the people involved in the CHARM study who have brought us that much closer to achieving our goal of advancing medicine for those in desperate need.”

Data from the CHARM study was presented at the 10th European Stroke Organization Conference, May 15-17 in Basel, Switzerland.

ABOUT REMEDY

New York-based Remedy Pharmaceuticals, Inc. is a privately-held, clinical stage pharmaceutical company focused on developing and bringing lifesaving treatments to people affected by acute central nervous system (CNS) disease and injuries. The company is planning a confirmatory Phase 3 study of CIRARA in LHI.

Contact:
Sven Jacobson
CEO
Remedy Pharmaceuticals
212.586.2226
sven@remedypharmaceuticals.com
www.remedypharmaceuticals.com

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From Setbacks to Breakthroughs: Remedy Pharmaceuticals' Unwavering Quest to Transform Stroke Treatment

Drug development is a complex and challenging endeavor, marked by years of struggle, hard work, disappointments, and occasional triumphs. The story of Remedy Pharmaceuticals and our innovative stroke treatment, CIRARA, is no exception.

Each year, approximately 700,000 Americans suffer from ischemic strokes (some 14 million worldwide), with a particularly devastating subset classified as Large Hemispheric Infarctions (LHI). These strokes, which account for 10-15% of all ischemic strokes, are characterized by large infarcts (typically more than 70mL — approximately half a tennis ball) which frequently leads to massive brain edema, brain tissue shifts, herniation, and death.

Despite advancements like the clot-buster drug, rtPA, and mechanical clot removal through endovascular therapy (EVT), functional outcomes for LHI remain poor, and mortality rates high.

Remedy’s drug, CIRARA, targets a critical regulator of cerebral edema, the SUR1-TRPM4 channel. During an ischemic stroke, SUR1-TRPM4 channels become upregulated and open due to ATP depletion, leading to sodium influx, cell swelling, and disruption of the blood-brain barrier. By inhibiting this channel, CIRARA prevents the formation of this damaging and often life-threatening edema, potentially offering a new lease on life for patients suffering from LHI.

The journey of CIRARA began with the discovery of the SUR1-TRPM4 channel by Dr. J. Marc Simard at the University of Maryland School of Medicine. The founders of Remedy Pharmaceuticals licensed the technology to develop CIRARA from a scientific finding into a life-saving therapy.

There were many steps along the way, from choosing the most effective molecule, to developing and testing the intravenous formulation, and devising a dosing regimen to optimize the unique pharmacokinetic properties of the drug. Then it was on to the clinic.

Early trials (a Phase 2a pilot study and the Phase 2b study known as GAMES-RP) provided promising signals, demonstrating reduced mortality and improved functional outcomes in LHI patients.

In 2017, while Remedy was in the midst of planning a Phase 3 study, Biogen acquired CIRARA, and in late 2018 launched the Phase 3 CHARM study. Despite passing an interim analysis designed to determine whether proceeding was futile, Biogen’s strategic shift away from acute neurology led to the premature termination of the study in 2023. The move came without warning to Remedy, the over 200 hospitals and medical centers around the world that were a part of the study, and the many hundreds of patients and their families who had agreed to participate.

Undeterred, Remedy Pharmaceuticals reclaimed the asset. Pre-specified analyses of the CHARM study data revealed compelling results: CIRARA demonstrated statistically significant efficacy in patients with an NIH Stroke Scale (NIHSS) ≤20 (n=274) with an Odds Ratio of 1.66 (p=0.03), and LHI patients who also underwent EVT appeared to particularly benefit, with an Odds Ratio of 1.75 in favor of CIRARA, although this was not statistically significant.

Further analyses showed that in patients with ischemic lesion volumes less than 125 mL, the Odds Ratio in favor of CIRARA was 2.15 (p=0.04). In patients with lesion volumes less than 125 mL undergoing EVT, the odds ratio was 7.13 (p=0.01) in favor of CIRARA underscoring its substantial impact on functional outcomes which was accompanied by a dramatic 81% reduction in mortality without increasing severe disability.

LHI is characterized by the development of life-threatening cerebral edema which causes the brain to shift past its center line, a phenomenon known as midline shift (MLS). MLS is associated with neurological deterioration and mortality, and MLS > 5 mm is considered a critical tipping point, indicating severe swelling and a higher risk of poor outcomes. In patients with lesion volumes less than 125 mL who underwent EVT, CIRARA reduced MLS at 72 hours by 41% (3.4mm vs 5.8mm, p=0.02). These findings were consistent with earlier results from the GAMES-RP study and reinforced that CIRARA could indeed become a game-changer in LHI treatment.

Thus, despite the setbacks, the story was far from over. With CIRARA squarely back in Remedy’s hands, we are ready to write the remaining chapters.

Looking ahead, Remedy is planning a pivotal Phase 3 trial that will confirm CIRARA’s effect in LHI patients with lesion volumes below 125 mL who undergo EVT. This carefully designed study will recruit 300 patients at 50 top-tier sites, in the U.S., Europe, Australia, Canada, and Israel. With an estimated cost of $50-$70 million and a target completion date in 2027, the trial seeks to build on the robust data already gathered, propelling CIRARA towards FDA and EMA approval.

The market potential for CIRARA is substantial, with an estimated annual value of over $3 billion. In the U.S. alone, the addressable market comprises approximately 75,000 LHI patients.  Between the patent portfolio developed by Remedy (both before the Biogen deal and after the asset’s return) and a new formulation patent developed by Biogen that is now owned by Remedy, the company has built a thicket of patent claims from multiple patent families, providing exclusivity by way of treatment method, dosing regimen, and formulation patents with expiry dates into the mid-late 2040s.

In the world of medicine, where each day can mean the difference between life and death, the stakes are incredibly high. So too is Remedy’s commitment. We have faced numerous obstacles and have emerged with a clear vision and an unwavering determination to see CIRARA through to its full potential. We are not just developing a drug for LHI; we are igniting hope of better days ahead for stroke patients and their families.

For now, we leave you with the words of Dr. Gregory W. Albers, Director of the Stanford Stroke Center, “After three decades of searching for an effective neuroprotective treatment, I believe we are finally on the verge of a breakthrough. CIRARA has more promising efficacy data than any of the previously tested agents.”