Ganaxolone is a synthetic neurosteroid and is being investigated as a first in class drug for the treatment of epilepsy.

In previous clinical studies, ganaxolone had been administered to more than 800 healthy adult volunteers and patients, 214 in Phase 1 studies, and approximately 500 patients in Phase 2 epilepsy and migraine studies. The epilepsy studies generated data supportive of ganaxolone's efficacy and safety in the treatment of both children and adults suffering from refractory epilepsy.

Marinus in-licensed ganaxolone and in December 2006, the Company successfully completed a study of a proprietary new liquid suspension formulation which is being investigated in Phase 2b clinical studies.

Ganaxolone for Partial Complex Seizures

As many as 30% of epilepsy patients may not have their epilepsy under control with current antiepileptic drugs (French JA, et al., 2004). The approach of adding an experimental anti-epileptic drug to an existing therapeutic regimen has proven to be a useful strategy for demonstrating efficacy of novel compounds.

Marinus is conducting Phase 2b studies of ganaxolone to study and evaluate safety, tolerability, and efficacy in adults with complex partial seizures. The study evaluates ganaxolone when used as an add-on therapy in adult patients with partial seizures which are inadequately controlled on their present anti-epileptic drug regimen. In March 2009, the company announced that it met its primary endpoint for the Phase 2a trial with ganaxolone demonstrating a statistically significant reduction in seizures versus placebo in this adult population.

To learn about our clinical trials, please click here.

References & Scientific Support

Ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one) is the 3β-methylated synthetic analog of the neurosteroid allopregnanolone, a metabolite of progesterone. Importantly, ganaxolone does not have significant classical nuclear steroid hormone activity and, unlike 3α,5α-P, cannot be converted to metabolites with such activity. Phase 1 and Phase 2 human trials indicate that ganaxolone is well tolerated and that it may be efficacious in the treatment of diverse forms of epilepsy in children and adults. (For substance summary, please click here.)

Pharmacology – A new class of anti-convulsant
Ganaxolone is a powerful positive allosteric modulator of GABA-A receptors with potency and efficacy comparable to the endogenous GABA-A receptor neuromodulator allopregnanolone (Carter et al., 1997). As with allopregnanolone, ganaxolone potentiation of the GABA-A receptor occurs at a site distinct from the benzodiazepine binding site. Ganaxolone has protective activity in diverse rodent seizure models, including clonic seizures induced by pentylenetetrazol (PTZ) and bicuculline (BIC), limbic seizures in the 6 Hz model, and amygdala kindled seizures (Carter et al., 1997; Rogawski and Reddy, 2004; Kaminski et al., 2004).