FDA Approve First Brain Gene Therapy PTC Kebilidi
-
by
Ree Webster
In a move that promises to improve the lives of American patients living with the rare disease aromatic l-amino acid decarboxylase (AADC) deficiency, the FDA has finally approved the effective gene therapy known as Kebilidi, developed by PTC Therapeutics, Inc.
Designed for the treatment of AADC deficiency in children and adults across the full spectrum of disease severity, Kebilidi ™, medically known as eladocagene exuparvovec-tneq, is a recombinant AAV-based gene therapy (or rAAV) that works by delivering a functional copy of the DDC gene to cells in a brain region called the putamen.
Without treatment, patients typically can not speak, have motor problems, and face severe developmental delays. The symptoms eventually lead to life-threatening complications such as infections, feeding and breathing problems, and autonomic dysfunction. AADC is fatal and dramatically reduces life expectancy, with a high risk of death by the age of 10.
Kebilidi was first developed in Taiwan, where it entered clinical trials in 2010. Over the years, 30 children received the treatment, which was later approved for use in 2022 throughout Europe and the UK, where it is available under the brand name Upstaza. Until November 2024, patients residing in the States had to seek alternative treatments. Fortunately, the FDA eventually accelerated approval of the first-ever gene therapy directly administered to the brain and finally gave Kebilidi the green light.
Matthew B. Klein, M.D., Chief Executive Officer, PTC Therapeutics said:
“PTC has once again pioneered a new approach to treating highly morbid neurologic diseases
“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.”
PTC is a global biopharmaceutical company, founded in 1998, that focuses on the “discovery, development and commercialization of clinically differentiated medicines” to benefit children and adults living with rare diseases and disorders. Known for developing the first gene therapy treatment in 2003, which was designed for another notoriously difficult-to-treat rare disease, Duchenne muscular dystrophy, it comes with little surprise that the company would go on to provide an equally effective gene therapy treatment for AADC deficiency.
What Is Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency?
AADC deficiency is a highly morbid and life-shortening rare genetic disorder that results in the inability to synthesize dopamine, a neurotransmitter essential for motor function typically causes severe disability and suffering from the first months of life, affecting every aspect of life—physical, mental and behavioral
Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency is a rare genetic disorder that disrupts the production of essential neurotransmitters, including dopamine and serotonin. These chemicals play a vital role in regulating movement, mood, and various bodily functions. AADC deficiency occurs due to mutations in the DDC gene, which impair the enzyme’s ability to convert amino acids into neurotransmitters.
This highly morbid and life-shortening rare genetic disorder dramatically affects the lives of children who are typically, severely impacted by the disease. Current treatment, administered in the form of physical, occupational and speech therapy, as well as surgical procedures, only offers patients a certain level of success in managing potentially life-threatening complications, however the new FDA approval of Kebilidi provides a more effective treatment method that will improve life expectancy and quality of life for many more patients.
What is Kebilidi and How Does it Work?
Kebilidi is a gene replacement therapy designed to correct the underlying genetic defect by delivering a functioning DDC gene directly into the putamen of the brain via stereotactic neurosurgical procedure.
Clinical trial results demonstrate that the gene therapy increases the AADC enzyme which in turn, leads to a de novo synthesis of dopamine (the creation of dopamine), effectively restoring dopamine production. This is then followed by the progressive acquisition of motor development milestones.
Kebilidi is administered utilizing a stereotactic surgical procedure; a minimally invasive neurosurgical procedure typically used in the treatment of several other pediatric and adult neurological disorders. The procedure is performed by a qualified neurosurgeon using the SmartFlow Neuro Cannula.
Donald Gilbert, MD, a clinician at Cincinnati Children’s who played a central role in treating Sriansh said:
“The way that a missing gene can be put in the brain in the place where it’s needed, in a single-day treatment, and then produce what is needed for the rest of a child’s life is amazing,”
Although the treatment was created with children in mind, it is important to note that Kebilidi should only be used in patients who have already reached a certain level of skull maturity. With that in mind, clinical trials have shown the treatment to be effective, and safe for children as young as 16 months, however there is currently no studies that look into the effects on patients younger than 16 months.
Officially approved 13th November 2024, launch preparations are well underway, with centers of excellence already identified and surgeons trained in the procedure to deliver the gene therapy.
