FDA Approves PTC Therapeutics’ Gene Therapy for AADC Deficiency

On Nov. 14, 2024, FDA announced its approval of eladocagene exuparvovec-tneq (Kebilidi, PTC Therapeutics), an adeno-associated virus vector-based gene therapy, for treating adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency (1). According to the agency’s press release, Kebilidi is the first FDA-approved gene therapy indicated for this disease.

Administration of the gene therapy is performed via four infusions during one surgical session into a large structure in the brain that is involved in motor control. FDA noted in its press release that Kebilidi should be administered in a medical center that specializes in pediatric stereotactic neurosurgery, which is a technique that uses imaging and special equipment to deliver therapies to specific areas in the brain. Following infusion, the treatment leads to expression of AADC and a subsequent increase in the production of dopamine, which is a critical neurotransmitter in the brain associated with movement, attention, learning and memory, according to the press release.

“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,” said Peter Marks, MD, PhD, director of FDA’s Center for Biologics Evaluation and Research (CBER), in the release (1). “Today’s approval underscores our commitment to help make safe and effective treatments available for patients in need.”

AADC deficiency is a rare genetic disorder that affects the production of some neurotransmitters, interfering with the body’s nervous system cells’ ability to communicate with each other. Symptoms include delays in gross motor function (head control, sitting, standing, and walking), hypotonia (weak muscle tone), and developmental and cognitive delays.

“AADC deficiency can cause a range of debilitating symptoms, including life-threatening complications,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in CBER, in the release (1). “[The] approval represents important progress in the advancement and availability of safe and effective treatments for debilitating genetic disorders.”

Eladocagene exuparvovec-tneq’s safety and effectiveness were demonstrated in an open-label, single-arm clinical study with 13 pediatric patients who had confirmed diagnoses of AADC deficiency. All patients at the start of the study were noted as having no gross motor function (the most severe presentation of AADC deficiency) and decreased AADC activity in the plasma. The patients treated with eladocagene exuparvovec-tneq were compared to untreated patients (natural history). At week 48 following treatment, motor milestone assessments were completed for 12 of the 13 patients. The efficacy of the gene therapy was demonstrated by evidence of improved gross motor function in eight out of 12 patients treated that was not reported in untreated patients with the severe presentation of AADC deficiency.

Eladocagene exuparvovec-tneq underwent an accelerated approval process, and its application received priority review, orphan drug designation, and was granted a rare pediatric disease priority review voucher by FDA. Continued approval for the AADC deficiency indication may be contingent upon the agency receiving verification and description of the clinical benefit of the product, such as the durability of improved symptoms, in a confirmatory clinical trial. Eladocagene exuparvovec-tneq is in an ongoing confirmatory trial to verify its clinical benefit.

In addition to the gene therapy product’s approval, FDA also authorized an infusion tube, the SmartFlow Neuro Cannula (ClearPoint Neuro) (2), which is inserted into a target in the brain (parenchymal tissue), for delivering eladocagene exuparvovec-tneq. FDA stated in its release that the SmartFlow Neuro Cannula is currently the only FDA authorized device indicated for use in the administration of eladocagene exuparvovec-tneq.

Reference

1. FDA. FDA Approves First Gene Therapy for Treatment of Aromatic L-amino Acid Decarboxylase Deficiency. Press Release. Nov. 14, 2024.
2. ClearPoint Neuro. ClearPoint Neuro Announces FDA De Novo Marketing Authorization of SmartFlow Cannula for Direct Delivery of Gene Therapy to the Brain. Press Release. Nov. 13, 2024.

Source: Food and Drug Administration