FDA Approves PTC Therapeutics' AADC Deficiency Gene Therapy

PTC Therapeutics, Inc., a biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for its gene therapy, KEBILIDI™ (eladocagene exuparvovec-tneq), for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. This is a groundbreaking approval as it marks the first-ever gene therapy in the United States to be directly administered to the brain.

Dr. Matthew B. Klein, CEO of PTC Therapeutics, expressed pride in the team’s dedication to achieving this regulatory milestone. He emphasized the significance of this new treatment option for both children and adults suffering from AADC deficiency. Launch preparations for KEBILIDI are in progress, with specialized centers and trained surgeons ready to deliver the gene therapy.

AADC deficiency is a severe, life-shortening genetic disorder characterized by the inability to produce dopamine, a neurotransmitter vital for motor function. KEBILIDI, a gene replacement therapy, is administered directly to the putamen region of the brain via a stereotactic neurosurgical procedure. Clinical trials have shown that the therapy leads to the de novo synthesis of dopamine and subsequent motor development milestones.

The FDA's accelerated approval of KEBILIDI was based on the safety and efficacy data from the ongoing global clinical trial (PTC-AADC-GT-002). Confirmatory evidence will be gathered from long-term follow-up studies of patients already treated with KEBILIDI.

In addition to the approval, PTC Therapeutics received a Rare Disease Priority Review Voucher, which the company plans to monetize.

AADC deficiency typically manifests in severe disabilities and distress from infancy, profoundly impacting physical, mental, and behavioral aspects of life. Children affected by this disorder may experience oculogyric crises, painful episodes resembling seizures, leading to a stuck upward gaze, dystonia, and inconsolability. The disorder necessitates continuous physical, occupational, and speech therapy, along with various interventions to manage life-threatening complications such as infections and severe feeding and breathing problems.

KEBILIDI™ (eladocagene exuparvovec-tneq) is a recombinant adeno-associated virus serotype 2 (rAAV2)-based gene therapy that contains the human DDC gene. It aims to correct the underlying genetic defect by delivering a functional DDC gene directly into the putamen, thereby increasing the AADC enzyme levels and restoring dopamine production. The therapy is administered through a minimally invasive stereotactic surgical procedure by a qualified neurosurgeon at specialized centers. The SmartFlow Neuro Cannula is utilized for the administration of KEBILIDI.

The gene therapy is indicated for both adult and pediatric patients with AADC deficiency under accelerated approval, contingent on the verification of clinical benefits in a confirmatory trial. Important safety information includes monitoring for procedural complications, potential dyskinesia, and adverse reactions such as pyrexia, hypotension, anemia, and others. The therapy is contraindicated for patients without skull maturity as assessed by neuroimaging.

PTC Therapeutics, Inc. is a global biopharmaceutical company dedicated to developing and commercializing medicines for rare disorders, aiming to provide best-in-class treatments for patients with limited options. The company leverages its scientific and clinical expertise and global commercial infrastructure to maximize value and deliver transformative therapies to patients.