10 May 2019 - - US-based specialty pharmaceutical company Eagle Pharmaceuticals, Inc. (NASDAQ: EGRX) has received positive results of its study to evaluate the neuroprotective effects of Ryanodex (dantrolene sodium) secondary to nerve agent exposure, conducted with the United States Army Medical Research Institute of Chemical Defense (USAMRICD), the nation's leading science and technology laboratory in the area of medical chemical countermeasures research and development, the company said.

The study results show a p-value of 0.04 or less compared to the control group in six critical areas of the brain.

We believe these results demonstrate the neuroprotective effects of Ryanodex.

It has been hypothesised that nerve agent poisoning triggers intracellular calcium release in the body. The study data supports the proposed mechanism of action of Ryanodex, which modulates intracellular calcium in different organs including the brain.

Eagle conducted an initial study in 2017 to evaluate the neuroprotective effects of Ryanodex in a rodent model of NA-induced brain damage.

Positive results of this study led to this GLP study to evaluate the efficacy of Ryanodex to reduce neuropathology in catheterized rats exposed to the nerve agent soman.

The study was conducted with the USAMRICD, at their laboratories in Aberdeen, Maryland, under a Cooperative Research and Development Agreement (CRADA), a written agreement that allows government laboratories to partner with private industries or academia on research and development projects.

The animal study was conducted in a rat model of acute nerve agent (soman) exposure. Animals were randomised into each of the six study groups, including a positive control and a negative control group. Five groups received standard treatment with HI-6, atropine and midazolam.

Four of the groups also received Ryanodex.

Surviving animals were evaluated for neuropathology 24 hours post-soman exposure to assess the neuroprotective effects of Ryanodex in this well-established animal model.

Scientific evidence indicates that elevated intracellular calcium levels may have a role in seizure-related brain damage resulting from induced seizures and status epilepticus secondary to NA exposure.

As in other conditions, including acute hyperthermic and hypermetabolic disorders, intracellular calcium overload leads to severe brain and other organ damage.

Ryanodex (dantrolene sodium) is a well-characterized ryanodine receptor antagonist that inhibits intracellular calcium overload secondary to different triggers. Ryanodine receptors are widely distributed in the body, including skeletal muscle, heart and brain tissues.

The active ingredient in Ryanodex is the only approved drug that inhibits the ryanodine receptors, modulating the intracellular calcium levels.

NAs were first widely used in World War II; their impact became a significant public health issue thereafter. NAs acquired their name because they affect the transmission of nerve impulses in the nervous system. NAs include compounds such as sarin, VX and soman.

NAs, whether gas, aerosol or liquid, are extremely toxic and have a very rapid effect.

The NA enters the body through inhalation or through the skin. Poisoning may also occur through consumption of liquids or foods contaminated with NAs. NA survivors will likely experience severe symptoms, including neurologic consequences.

NAs produce seizures and seizure-related brain damage. The seizures quickly develop into status epilepticus and usually become refractory to standard antiepileptic therapy.

At present, antidotes for nerve agent exposure provide limited protection, and current treatments do not fully reduce nerve-agent-induced seizures and subsequent brain injury.

Additionally, medical care for NA casualties is likely to be delayed beyond the therapeutic window of opportunity to terminate NA-induced seizures, resulting in seizure-related brain damage that continues along the pathological cascade.

Thus, there is a need for adjunct drug therapy that is capable of interrupting the pathologic cascade and augmenting neuroprotection when administered in combination with antiepileptic drugs during the refractory phase of NA-induced seizures.

Scientific evidence supports a pivotal role of elevated intracellular calcium levels in seizure-related brain damage resulting from induced seizures and status epilepticus secondary to NA exposure.

In addition, there are several reports that a neuroprotective approach, aimed at attenuating delayed calcium overload, combined with antiepileptic treatment, may lead to greater protection against seizure-related brain damage than anti-epileptics alone.

Eagle is a specialty pharmaceutical company focused on developing and commercializing injectable products that address the shortcomings, as identified by physicians, pharmacists and other stakeholders, of existing commercially successful injectable products.

Eagle's strategy is to utilise the FDA's 505(b) (2) regulatory pathway.