Ganaxolone’s Approval Springboards Future CDD Drug Development: Elia Pestana-Knight, MD

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"One of the characteristics of the disease is that the patients exhibit a variable and low response to traditional antiseizure medications. Even sometimes when you get a response over the following 3 months, you lose that response. There is a high lack of efficacy and loss of efficacy to the traditional antiseizure medications."

CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental condition caused by pathogenic variants in the CDKL5 gene, which is responsible for creating a protein necessary for normal brain development and function. The disorder can cause a wide range of symptoms with varying severity, making it one of the more complex encephalopathies out there. Seizure control remains a challenge for patients with the disorder and has historically been addressed through a combination of several antiseizure medications (ASMs).

After years of finding little drug development success, the field had a major breakthrough. In March 2022, the FDA approved ganaxolone (Ztalmy; Marinus Pharmaceuticals) as the first treatment for patients with CDD. Ganaxolone, a neuroactive steroid that acts as a positive allosteric modulatory of the GABAA receptor, was approved based on data from the phase 3 Marigold trial (NCT03572933), a double-blind placebo-controlled trial that randomized 101 patients with the disorder.¹ Primary investigator Elia Pestana-Knight, MD, who presented some of the data from Marigold at the 2022 American Academy of Neurology (AAN) annual meeting, believes there is good reason to celebrate the approval.

Pestana-Knight, a pediatric epileptologist at Cleveland Clinic, noted that drug development is of high importance for this patient group, considering the severity of their refractory seizures. As part of NeurologyLive®’s coverage of AAN 2022, she sat down to discuss the implications of the approval, ganaxolone’s unique mechanism of action, and how it can hopefully springboard future drug development.

For more coverage of AAN 2022, click here.

REFERENCE
1. Olson H, Moosa AN, Rybak E, et al. Extended Duration Safety and Efficacy of Adjunctive Ganaxolone Treatment in Patients with CDKL5 Deficiency Disorder: 8-Month Minimum Open-Label Extension Follow-up. Presented at: AAN Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual. Abstract 003540.