Positive Findings in Phase 2 Study of Refractory Status Epilepticus Drug Candidate

According to a recent press release from the Pennsylvania-based Marinus Pharmaceuticals, the Company is reporting positive results of its phase 2 study of “ganaxolone,” an investigational GABAA modulator for patients with refractory status epilepticus.

About Refractory Status Epilepticus

Refractory status epilepticus (RSE) is, as its name implies, a kind of treatment-resistant status epilepticus. Status epilepticus is a serious condition characterized by long-lasting seizures that continue for over five minutes (if convulsive, 30 if not), or by a rapid succession of shorter seizures without recovering. Short-term morbidity rates are high, with estimates ranging between 16% and even 39%.

Status epilepticus is dangerous, and anyone experiencing a status epilepticus seizure needs emergency medical care as soon as possible. If the individual cannot be sufficiently stabilized, and quickly, permanent brain damage or death can occur.

Currently employed standards for stabilizing status epilepticus include benzodiazepines and anti-epileptics, most often in the form of an intravenous (IV) solution. Patients are considered to be in refractory status epilepticus when two or more anti-epileptic drugs fail to end the seizure. In certain cases, doctors may attempt to induce a coma to end the episode. But this is uncharted territory — currently, there are no treatments indicated for RSE.

Every year there are as many as 150,000 diagnoses of status epilepticus in the United States, resulting in as many as 55,000 deaths. Some estimates suggest that as many as 30% of status epilepticus patients have refractory forms.

About Ganaxolone, an RSE Drug Candidate

Ganaxolone is an intravenously-administered GABAA modulator. GABAA is an ion channel that plays a key role in the regulation of nerve firings by controlling the flow of chloride ions into and out of nerve cells. As the cell builds up an internal charge to fire a nerve impulse, chloride ions, which carry a negative charge, flow into the cell through GABAA channels — counteracting the ability of the cell to build up the required electric disparity to transmit a signal. After the cell does fire, chloride flows back out through the GABAA channel.

By modulating these GABAA receptors, researchers believe it may be possible to control the amount of chloride entering or leaving a patient’s nerve cells. The thinking is that by controlling nervous chloride levels, physicians could control overactive nerve firing that is characteristic of seizures.

In a phase 2 study, ganaxolone was found to be safe and generally well-tolerated in participants. Volunteers also demonstrated positive health trends, often requiring no additional anti-epileptic drugs or anesthetics for 48 hours after infusion. Additional corroborating research will be necessary (just 17 patients participated in the phase 2 study), but preliminary findings have some excited.

“I believe these data may represent the emergence of a new treatment paradigm for RSE,” said Dr. Henrikas Vaitkevicius, a study investigator, Neurologist at Brigham and Women’s Hospital, and Assistant Professor at Harvard Medical School.

Marinus is planning and end-of-phase 2 meeting with the US Food and Drug Administration (FDA) to discuss a potential follow-up phase 3 study.


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