FDA Approves Kebilidi, First Gene Therapy for AADC Deficiency

• The FDA has granted accelerated approval to Kebilidi (eladocagene exuparvovec-tneq) for treating Aromatic L-Amino Acid Decarboxylase (AADC) deficiency in adults and children.
• Kebilidi, an adeno-associated virus vector-based gene therapy, is the first FDA-approved treatment of its kind for this rare genetic disorder affecting neurotransmitter production.
• Clinical trials demonstrated that Kebilidi improved gross motor function in pediatric patients compared to untreated individuals, marking a significant advancement in managing this debilitating condition.
• Administered via targeted infusions into the brain, Kebilidi represents a crucial step forward in providing innovative therapies for rare and difficult-to-manage diseases.

The U.S. Food and Drug Administration (FDA) has approved Kebilidi (eladocagene exuparvovec-tneq) for the treatment of both adult and pediatric patients suffering from Aromatic L-Amino Acid Decarboxylase (AADC) deficiency. This marks a significant milestone as Kebilidi becomes the first FDA-approved gene therapy for this rare genetic disorder.

AADC deficiency disrupts the production of key neurotransmitters, which are vital for communication within the nervous system. This deficiency can lead to severe developmental delays, weak muscle tone (hypotonia), and impaired motor function. The approval of Kebilidi offers a new therapeutic avenue for patients who currently have limited treatment options.

Clinical Efficacy

The approval was based on data from an open-label, single-arm clinical study involving 13 pediatric patients diagnosed with AADC deficiency. At the study's outset, all patients exhibited the most severe form of the condition, lacking gross motor function and displaying reduced AADC activity in plasma. Impressively, 8 out of 12 patients treated with Kebilidi showed notable improvements in gross motor function at week 48 when compared to the natural progression of untreated patients.

According to Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER), "Clinical advancements in the field of gene therapy continue to lead to the discovery and availability of innovative treatment options for rare diseases that are otherwise difficult to manage."

Administration and Safety

Kebilidi is administered through four infusions during a single surgical session, targeting a specific region of the brain responsible for motor control. The most common adverse reactions observed during clinical trials included dyskinesia, fever, low blood pressure, anemia, increased saliva production, and insomnia. The therapy is contraindicated in patients with immature skull development, as determined by neuroimaging.

The FDA also authorized the SmartFlow Neuro Cannula, an infusion tube inserted into a target in the brain (parenchymal tissue), to deliver Kebilidi. The SmartFlow Neuro Cannula is currently the only FDA authorized device indicated for use to administer Kebilidi. The FDA granted authorization of the SmartFlow Neuro Cannula to ClearPoint Neuro.

Regulatory Context

Kebilidi received accelerated approval, a pathway the FDA uses to expedite the availability of treatments for serious conditions where there is an unmet medical need. The drug also received Priority Review and Orphan Drug designation, and was granted a rare pediatric disease priority review voucher. The approval was granted to PTC Therapeutics.