FDA Approves Kebilidi, First Brain-Delivered Gene Therapy for AADC Deficiency

• The FDA has approved Kebilidi (eladocagene exuparvovec), a gene therapy for AADC deficiency, marking the first brain-delivered gene therapy approved in the US.
• Kebilidi replaces the mutated DDC gene, enabling dopamine synthesis and addressing severe motor and neurological symptoms in children and adults with AADC deficiency.
• Clinical trials demonstrated that Kebilidi allows patients to achieve developmental motor milestones, such as walking and talking, not typically seen in AADC deficiency.
• PTC Therapeutics plans to launch Kebilidi in the US, with treatment centers identified and physicians trained, and intends to sell the priority review voucher (PRV) granted by the FDA.

The FDA has granted approval to Kebilidi (eladocagene exuparvovec), a gene therapy developed by PTC Therapeutics for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. This marks a significant milestone as the first gene therapy approved for direct administration into the brain. Kebilidi is indicated for both children and adults with AADC deficiency, a rare and fatal genetic disorder characterized by the inability to synthesize dopamine, leading to severe motor and neurological impairments.

Mechanism of Action and Clinical Efficacy

Kebilidi functions by delivering a functional copy of the human dopa decarboxylase (DDC) gene directly into the putamen area of the brain. This gene replaces the mutated DDC gene responsible for AADC deficiency, thereby enabling dopamine synthesis. Clinical data supporting the approval of Kebilidi were primarily generated from unblinded studies conducted in Taiwan, involving 28 children aged between 18 months and eight years. The results demonstrated that patients treated with Upstaza (European brand name for eladocagene exuparvovec) achieved developmental motor milestones, such as independent walking and speech, which are typically unattainable for individuals with AADC deficiency.

Impact on AADC Deficiency Treatment

Prior to the approval of Kebilidi, there were no approved therapies available in the US for AADC deficiency. This condition affects approximately 350 reported cases worldwide, with a significant proportion of patients having Asian ancestry. AADC deficiency results in a range of debilitating symptoms, including seizures, developmental delays, and a high risk of mortality within the first decade of life. The approval of Kebilidi offers a potentially transformative treatment option for these patients, addressing a critical unmet medical need.

Commercialization and Future Prospects

PTC Therapeutics is preparing to launch Kebilidi in the US, with identified treatment centers and trained physicians ready to administer the therapy. The gene therapy was previously approved in the EU in July 2022 and the UK in November 2022. The company reported $13 million in revenue from Upstaza in 2022 through early access programs and commercial sales. Analysts estimate that US approval could drive peak sales to nearly $275 million. Furthermore, the FDA approval grants PTC a priority review voucher (PRV), which can be sold for upwards of $100 million, providing additional financial flexibility for the company.

Matthew Klein, CEO of PTC, stated that the company has "pioneered a new approach to treating highly morbid neurologic diseases" and expressed pride in bringing this "transformational gene therapy" to patients with AADC deficiency in the US.