BARDA and Marinus Pharmaceuticals have begun a collaboration to develop ganaxolone (GNX) to treat seizures that are not stopped by first-line anticonvulsants like benzodiazepines. This treatment could potentially stop damaging seizures no matter the underlying medical etiology, including seizures that result from exposure to nerve agents like Sarin.
Unremitting continuous or near-continuous seizures (also called status epilepticus or SE) are a life-threatening condition that can lead to permanent brain damage and disability. SE can arise from a range of underlying medical etiologies or from exposure to chemical weapon nerve agents. Limited FDA-approved treatments for SE are available; generally, intravenous antiepileptic drugs are used to terminate the seizures. However, 30% to 50% of cases may progress to refractory SE, i.e. are not successfully treated with available first- or second-line anticonvulsants, and may require IV anesthetics to stop seizures.
Marinus recently completed a Phase II clinical study of GNX for refractory SE. None of the 17 patients in the study progressed to treatment with IV anesthesia, and 16 of the 17 remained free of SE for 24 hours following initiation of treatment. The new partnership between BARDA and Marinus will support studies, including a pivotal, large-scale Phase III clinical trial to support regulatory approval of GNX for the treatment of refractory SE, as well as non-clinical studies of nerve agent-induced refractory seizures. Marinus will also work to bring production of GNX into the United States.
Organophosphate nerve agents (chemical warfare agents and organophosphate-based pesticides) are highly toxic compounds, which cause overstimulation of the body’s central and peripheral nervous system. One consequence of this is seizures that may be prolonged and become more difficult to treat as they continue. The U.S. government fields benzodiazepine anticonvulsants as nerve agent antidotes; however, if treatment is delayed as is possible in a mass-exposure situation, those drugs may be less effective at stopping the seizures. GNX stops seizures by a slightly different mechanism than benzodiazepine anticonvulsants; the two drugs may work in a complementary fashion to stop seizure. In this way, GNX may be able to treat unremitting seizures when other drugs have failed, with the potential to save lives and improve long-term health outcomes for people exposed to nerve agents.
If FDA approves GNX, it could become the standard of care for treating refractory seizures. Widespread use for the treatment of refractory SE from a range of underlying medical conditions in communities across the country would ensure the drug’s broad availability in the event of a public health emergency involving mass exposure to nerve agent. By leveraging commonly available drugs to treat the effects of accidental or intentional chemical threat agent exposures, BARDA helps the nation prepare for public health emergencies as cost-efficiently as possible, and can make products available that healthcare providers are familiar with and comfortable using should the need ever arise.
The following information is provided by the company and does not indicate endorsement by the federal government of the company or its products.
Marinus Pharmaceuticals, Inc. is a pharmaceutical company dedicated to the development of innovative therapeutics to treat rare seizure disorders. Ganaxolone is a positive allosteric modulator of GABAA receptors that acts on a well-characterized target in the brain known to have antiseizure, antidepressant, and anti-anxiety effects. Ganaxolone is being developed in IV and oral dose forms intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus is conducting the first ever Phase 3 pivotal trial in children with CDKL5 deficiency disorder, along with a Phase 2 trial in tuberous sclerosis complex, and a Phase 2 biomarker driven proof of concept trial in PCDH19-related epilepsy. The company is planning to initiate a Phase 3 trial in refractory status epilepticus.