FDA Approves Eladocagene Exuparvovec-Tneq for Treatment of AADC Deficiency

The FDA approved eladocagene exuparvovec-tneq (Kebilidi; PTC Therapeutics Inc) for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. Eladocagene exuparvovec-tneq is an adeno-associated virus vector-based gene therapy and became the first FDA-approved gene therapy for AADC deficiency.¹

FDA Approval, Neurology, AADC Deficiency | Image Credit: Aquir | stock.adobe.com

“AADC deficiency can cause a range of debilitating symptoms, including life-threatening complications,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the Center for Biologics Evaluation and Research at the FDA, said in a statement. “Today’s approval represents important progress in the advancement and availability of safe and effective treatments for debilitating genetic disorders.”¹

AADC deficiency is a rare genetic disorder, with most affected individuals developing symptoms within the first months of life. Symptoms can include abnormal eye movement, movement disorders, and autonomic dysfunction. Furthermore, the disorder can cause mood disturbances, such as irritability and anxiety, but brain MRIs typically show normal or non-specific abnormalities. For those affected, there is a decreased activity of aromatic l-amino acid decarboxylase, an enzyme involved in synthesizing nurotransmitters.²

The approval was based on an open-label, single-arm clinical trial among 13 pediatric individuals with AADC deficiency. At the initiation of the study, all individuals had no gross motor functions and decreased AADC activity. Investigators compared eladocagene exuparvovec-tneq versus no treatment, with motor assessments completed for 12 of 13 of the patients at week 48. The data showed that gross motor function improved in 8 of 12 treated individuals versus no untreated patients, according to the FDA. The most common adverse events included dyskinesia, fever, low blood pressure, anemia, increased saliva production, insomnia, low levels of potassium, phosphate, and magnesium, and procedural complications.¹

According to the clinical trial information, the study will include an extension and long-term extension phase. The extension phase evaluated the clinical information, including change in motor development, AADC-specific symptoms, and other pharmacodynamic measures, and the long-term extension will include long-term safety and efficacy data for patients treated with the drug.³

Eladocagene exuparvovec-tneq is administered as 4 infusions in 1 surgical session into the part of the brain involved in motor control. It is administered in a medical center that specializes in pediatric stereotactic neurosurgery, which involves specific equipment to deliver the therapy to the brain. According to the FDA, after the infusion, expression of AADC increases the production of dopamine, which is associated with movement, attention, learning, and memory.¹

Previously, in May 2024, the FDA accepted the biologics license application for the drug and granted the application rare disease priority review.^4,5

REFERENCE

1. FDA Approves First Gene Therapy for Treatment of Aromatic L-amino Acid Decarboxylase Deficiency. FDA. News release. November 14, 2024. Accessed November 14, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-aromatic-l-amino-acid-decarboxylase-deficiency

2. National Organization for Rare Disorders. Aromatic L-Amino Acid Decarboxylase Deficiency. Updated November 14, 2024. Accessed November 14, 2024. https://rarediseases.org/rare-diseases/aromatic-l-amino-acid-decarboxylase-deficiency/

3. Boston Children’s Hospital. A Study of SmartFlow Magnetic Resonance (MR) Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Participants. November 13, 2024. Accessed November 14, 2024. https://www.childrenshospital.org/clinical-trials/nct04903288

4. PTC Therapeutics Announces FDA Acceptance and Priority Review of the BLA for Upstaza. News release. PTC Therapeutics Inc. May 14, 2024. Accessed November 14, 2024. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-fda-acceptance-and-priority-review-of-the-bla-for-upstaza-302144369.html

5. PTC Therapeutics Announces FDA Approval of AADC Deficiency Gene Therapy. News release. PTC Therapeutics. November 13, 2024. Accessed November 14, 2024. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-approval-aadc-deficiency-gene