Human Study Shows Remedy Pharmaceuticals, Inc.’ CIRARA Is Key To Preventing Brain Swelling In Stroke

In the first week of an ischemic stroke, 78% of deaths are attributable to swelling. Is CIRARA the miracle treatment for victims of stroke? Results of a clinical trial in severe stroke patients expected in September will answer that question.

NEW YORK--(BUSINESS WIRE)--Remedy Pharmaceuticals, a company focused on the development and commercialization of CIRARA™, a breakthrough drug for treating acute central nervous system conditions such as stroke, today announced publication of a peer-reviewed paper¹ that confirms administering CIRARA for pharmacologic targeting of the Sur1-Trpm4 channel in human ischemic stroke to reduce blood-brain barrier disruption and cerebral edema is a promising therapeutic strategy.

16 MILLION STROKE VICTIMS EACH YEAR; SWELLING IS THE LEADING CAUSE OF DEATH

Stroke is the second leading cause of death globally, with approximately 16 million victims each year.² About a third of all strokes result in death, and another third in permanent disability. Stroke occurs when the supply of blood to the brain is either interrupted or reduced. When this happens, brain cells start to die almost immediately. Edema, or swelling, is the body's response to many types of injury, including injury to the brain, as in a stroke. In fact, edema is one of the biggest mortality risks associated with stroke. In the first week of an ischemic stroke, caused by a blockage in the blood vessels supplying blood to the brain, 78% of all deaths are attributable to edema. In hemorrhagic stroke, or bleeding in the brain, 93% of deaths in the first week are caused by swelling.³

STUDY LINKS UPREGULATION OF CHANNEL TO SWELLING IN STROKE PATIENTS

Investigators at University of Maryland analyzed ischemic lesions in brain specimens from 13 ischemic stroke victims who died and underwent autopsy. For comparison, contralateral cortex samples were evaluated as control tissue. Brain specimens from 6 patients with documented absence of ischemic stroke also were examined as controls. Investigators found that the Sur1-Trpm4 cation channel, which is not constitutively present in (CNS) nervous system tissues, was transcriptionally upregulated in infarcted brain cortexes, but not in non-infarcted cortexes.

Sur1-Trpm4 channels have previously been shown to be upregulated de novo under neuropathologic conditions, such as in a stroke. These channels otherwise lie dormant in the endothelial cell membrane, doing no harm unless they are opened by depletion of intracellular energy. Channel opening leads to sustained influx of sodium, which, if unchecked, leads to formation of life threatening space-occupying edema. Prior molecular evidence of their expression in ischemic stroke was based on animal models, and this is the first time these channels have been proven to be upregulated in human ischemic stroke.

A ROLE FOR CIRARA IN CLOSING THIS CHANNEL

This study and other findings suggest an important role for the Sur1-Trpm4 channel in the pathophysiology of stroke and implicate pharmacologic blockade of the channel as a possible novel therapeutic strategy for mitigating malignant cerebral edema in patients sustaining large territorial cerebral infarction. Convincing evidence from preclinical and human clinical studies establish that Remedy Pharmaceuticals’ drug candidate, CIRARA, closes this channel, inhibiting cerebral edema, which is a significant contributor to mortality and poor patient outcomes.

CIRARA TRIAL RESULTS COULD BE A GAME CHANGER FOR STROKE VICTIMS

On May 5, Remedy announced it had successfully ended enrollment in GAMES-RP, a Phase 2, randomized double blind, placebo-controlled, multi-center trial of CIRARA in severe stroke patients. Results from the study are expected in September of this year. GAMES-RP follows a highly-successful pilot trial completed in 2012 involving patients with severe stroke who in over 80% of cases, would be expected to experience major brain swelling. In stark contrast, 90% of patients in the pilot study survived without severe disability, a reversal of the dire natural history of severe stroke. Follow up MRI images were notable for qualitative findings including absence of mass effect, and preservation of white matter.

ABOUT REMEDY PHARMACEUTICALS

Remedy Pharmaceuticals, Inc. is a privately-held, clinical stage pharmaceutical company focused on bringing life saving treatment to millions of people affected by acute central nervous system conditions -- including stroke, traumatic brain injury, spinal cord injury, as well as other ischemic injuries and neurological disorders.

¹ Mehta RI et al. Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts. J Neuropathol Exp Neurol. 2015 Aug;74(8):835-49.

² Krishnamurthi RV et al. Global and regional burden of first ever ischaemic and haemorrhagic stroke during 1990-2010. Lancet Global Health. 2013:1:e259-81

³ Silver FL et al. Early mortality following stroke: a prospective review. Stroke. 1984 May-Jun;15(3):492-6