Kebilidi: A Groundbreaking Gene Therapy Offering Hope for Rare Neurodevelopmental Disorder

The US Food and Drug Administration (FDA) approved the latest multimillion gene therapy. On November 13, 2024, the FDA approved Kebilidi (eladocagene exuparvovec-tneq), a gene therapy to treat an ultrarare condition called AADC deficiency.  A launch date or price for  Kebilidi has yet to be announced. However, the gene therapy is approved in the European Union under the brand name Upstaza and is priced at around £3 million, equating to approximately $3.75 million. A similar price point could be expected.

What is AADC deficiency?^1,2

AADC is an ultrarare neurodegenerative disease caused by a mutation in the dopa decarboxylase (DDC) gene. The DDC gene is important in making the AADC enzyme, which plays important roles in brain and nervous system function. Fewer than 350 patients have been reported in the medical literature with AADC deficiency, with an estimated US prevalence of 1-2 cases in every 1,000,000 live births. The quality of life of patients with the disease is low, and there are no treatments for AADC deficiency available today beyond gene therapy.

AADC deficiency symptoms can begin shortly after birth or a few months old. Due to the inability to produce normal enzymes for brain and nervous system function, patients experience severe disability and developmental delays. Many cannot sit up, crawl, walk, or talk at normal milestone developments. Due to the rarity of patients impacted by AADC deficiency, life expectancy is uncertain, but patients are at a high risk of early death in the first decade of life.

How does Kebilidi fit into the treatment options available for AADC deficiency?

Treatments for AADC deficiency have historically been limited to supportive care. Therapies most frequently used are to increase dopamine that patients cannot develop or decrease other enzymes that patients can’t break down. A multidisciplinary approach is recommended to help patients and their caregivers, including occupational or physical therapy, speech therapy, diet and nutrition, social work, and behavioral health providers. ^1,2

How does Kebilidi work?^3,4

Kebilidi is the first FDA-approved gene therapy administered directly into the brain. The therapy delivers a functional copy of the DDC gene to patients, allowing the patient to have functional production of the AADC enzyme.

Kebilidi was approved based on Phase I/II studies in 13 patients as young as 16 months old confirmed with AADC deficiency and skull maturity to withstand surgery. Of the 13 patients studied, 12 had severe phenotypic AADC deficiency, defined as not having any motor milestone achievements, and did not respond to standard of care prior to Kebilidi infusion. Gross motor milestones were assessed at week 48 after Kebilidi treatment. The results are summarized as follows:

• 8 of the 12 patients achieved new gross motor milestones
  • 3 patients achieved full head control
  • 2 patients achieved sitting with or without assistance
  • 2 patients achieved walking backward
  • 1 patient achieved the ability to sit unassisted
• 4 patients did not achieve new gross motor milestones
• 1 patient dropped out before follow-up at week 48

What does it mean for payers?

There are several considerations for the AADC deficiency patient population.

• The risk to payers may be lower due to the rarity of AADC deficiency.
• Diagnosis for AADC deficiency could be delayed or misdiagnosed because of its rarity in prevalence, low number of experienced specialists in the US, and not having a standard newborn screening for AADC deficiency in the US at this time. AADC deficiency is very rare, with most case studies in Taiwan.
• Kebilidi will have a life-changing impact on patients, caregivers, and families of those affected by AADC deficiency. Long-term outcomes for the use of Upstaza in the European Union provide positive impact and survival rates for patients with AADC⁵.
• Upstaza was approved in 2022 in the European Union. However, there are still unknown cost offsets for gene therapy.

With a robust pipeline and newly approved drugs for prevalent diseases, information about gene therapies is constantly changing. Payers need access to experts and analytics that are well-informed by the latest market insights.

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References:

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

[2] Figueiredo, Marta PhD. What is AADC Deficiency? BioNews, Inc. Pensacola, FL. Last Updated November 10, 2023. https://aadcnews.com/what-is-aadc-deficiency/.

[3] PTC Therapeutics Press Release. PTC Therapeutics Announces FDA Approval of AADC Deficiency Gene Therapy. November 13, 2024. Warren, NJ. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-approval-aadc-deficiency-gene

[4] Kebilidi Prescribing Information. PTC Therapeutics, Inc. Warren, NJ. November 2024

[5] Simons, Claire, et al. Long Term Outcomes of Eladocagene Exuparvovec Compared with Standard of Care in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency: A Modeling Study. https://doi.org/10.1007/s12325-023-02689-6. Accessed November 18, 2024.