AADC deficiency gene therapy, called Kebilidi, now approved in US
Kebilidi becomes first FDA-approved treatment for AADC deficiency
The U.S. Food and Drug Administration (FDA) has approved PTC Therapeutics’ one-time gene therapy, now called Kebilidi (eladocagene exuparvovec-tneq) in the U.S., for children and adults with AADC deficiency across the full spectrum of disease severity.
The decision makes Kebilidi, also approved under the brand name Upstaza in Europe and the U.K., the first treatment for AADC deficiency to be granted FDA approval and the first gene therapy approved in the U.S. that is directly administered to the brain.
The therapy has been granted accelerated approval allowing its use based on preliminary data from current clinical trials. However, continued approval may be contingent upon confirming its effectiveness and benefits based on data from long-term follow-up of those already treated as well as subsequent clinical studies.
Specialist centers selected, with surgeons trained to administer Kebilidi
According to the company, launch plans are underway, with specialist centers selected and surgeons trained to administer the gene therapy.
“PTC has once again pioneered a new approach to treating highly morbid neurologic diseases,” Matthew B. Klein, MD, CEO of PTC Therapeutics, said in a company press release. “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.”
AADC deficiency is caused by mutations in the DDC gene. This gene provides instructions to make the AADC enzyme, which is needed to manufacture certain neurotransmitters, which are signaling molecules that nerve cells in the brain use to communicate with each other and the rest of the body. Lacking the AADC enzyme means the brain cannot make enough neurotransmitters, leading to problems with neurological signaling that ultimately give rise to disease symptoms such as movement impairment and cognitive difficulties.
Kebilidi uses a modified version of a virus, adeno-associated virus serotype 2 (AAV2), to deliver a healthy version of the DDC gene to brain cells, thereby allowing cells to make functional AADC enzyme and ultimately facilitating production of neurotransmitters to ease symptoms.
Kebilidi administered directly into brain through one-time surgical procedure
The gene therapy is administered directly into the brain through a one-time surgical procedure, which is performed by a qualified neurosurgeon at a specialized center. The procedure uses a device called the SmartFlow Neuro Cannula, which has been specifically authorized for administering Kebilidi.
Although the gene therapy is approved for children and adults, its administration is contraindicated in patients who have not yet achieved skull maturity, or the stage at which the bones in the skull have fully developed.
PTC applied for approval of Kebilidi earlier this year, and the FDA granted the application priority review, shortening the review time from the usual 10 months down to six.
PTC’s application was based on data from multiple studies including a Phase 1/2 trial (NCT01395641) that launched in 2014 and a Phase 2b trial (NCT02926066) that began in 2016, as well as a compassionate use program. Data from these studies have indicated that Kebilidi treatment eased symptom severity and led to long-term improvements in motor function.
The gene therapy has been approved in the European Union and the U.K. since 2022 for people with AADC deficiency who are 18 months and older.
Alongside the therapy’s approval, PTC Therapeutics also received a Rare Disease Priority Review Voucher, which could expedite the review process for another one of their future therapies targeting rare diseases.
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