FDA Approves PTC Therapeutics’ Kebillidi for Aromatic L-Amino Acid Decarboxylase Deficiency

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The FDA has approved PTC Therapeutics’ Kebillidi (eladocagene exuparvovec-tneq) for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. According to the government agency, this marks the first gene therapy to be approved in the United States for AADC deficiency. The approval was based on clinical evidence from a single-arm study, which demonstrated motor milestone gains in a majority of patients.¹

"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 the FDA Center for Biologics Evaluation and Research (CBER), in a press release. "Today's approval underscores our commitment to help make safe and effective treatments available for patients in need."

The single-arm study consisted of 13 pediatric patients with a confirmed diagnosis of AADC deficiency. At study launch, all patients had no gross motor function and decreased AADC activity in the plasma. All treated patients were compared to untreated patients.

After 48 weeks of treatment, 12 out of the 13 patients had completed motor milestone assessments. Final results found that Kebillidi demonstrated gross motor function improvement in eight of 12 treated patients, which has not been reported in untreated patients with the severe presentation of AADC deficiency.

Common adverse events associated with Kebillidi included dyskinesia, fever, low blood pressure, anemia, increased saliva production, insomnia, low levels of potassium, phosphate, and/or magnesium, and procedural complications such as respiratory and cardiac arrest.1 Kebillidi is contraindicated in patients who have not achieved skull maturity assessed by neuroimaging. PTC warns that skull maturity is needed for stereotactic neurosurgical administration.⁴

"AADC deficiency can cause a range of debilitating symptoms, including life-threatening complications," said Nicole Verdun, MD, director, office of therapeutic products in CBER, in the press release. "Today's approval represents important progress in the advancement and availability of safe and effective treatments for debilitating genetic disorders."

According to the National Organization for Rare Disorders (NORD), AADC is an extremely rare disorder, with only 350 cases reported in medical literature. Nearly half of patients with AADC are Asian, and one-fifth are people with Taiwanese ancestry. Males and females seem to be equally affected. NORD also stated the belief that AADC is most likely underdiagnosed. In the United States, prevalence is based on cerebrospinal fluid analysis and genetic testing is roughly 1-2:1,000,000 live newborns.²

According to Medline Plus, AADC is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell must have a variant to cause the disorder. Additionally, both parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.³

Kebillidi was approved under the Accelerated Approval Pathway, with continued authorization depending on confirmatory trial results. Additionally, the treatment received Priority Review, Orphan Drug, and rare pediatric disease designations.

"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases," said Matthew B. Klein, MD, CEO, PTC Therapeutics. "I am proud of our team's unwavering commitment to achieve this important regulatory milestone. We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."⁴

References

1. FDA Approves First Gene Therapy for Treatment of Aromatic L-amino Acid Decarboxylase Deficiency. PR Newswire. November 14, 2024. Accessed November 15, 2024. https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-treatment-of-aromatic-l-amino-acid-decarboxylase-deficiency-302305795.html

2. Aromatic L-Amino Acid Decarboxylase Deficiency. NORD. Accessed November 15, 2024. https://rarediseases.org/rare-diseases/aromatic-l-amino-acid-decarboxylase-deficiency/

3. Aromatic l-amino acid decarboxylase deficiency. Medline Plus. Accessed November 15, 2024. https://medlineplus.gov/genetics/condition/aromatic-l-amino-acid-decarboxylase-deficiency/#inheritance

4. PTC Therapeutics Announces FDA Approval of AADC Deficiency Gene Therapy. PTC Therapeutics. November 13, 2024. Accessed November 15, 2024. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-approval-aadc-deficiency-gene