PTC Therapeutics Announces FDA Approval of AADC Deficiency Gene Therapy
PTC Therapeutics (NASDAQ: PTCT) has received FDA accelerated approval for KEBILIDI™, the first-ever gene therapy directly administered to the brain for treating AADC deficiency. The therapy is approved for both children and adults across all disease severity levels.
KEBILIDI is administered through stereotactic neurosurgery to the putamen of the brain, enabling dopamine synthesis and progressive motor development improvement. The approval is based on ongoing clinical trial PTC-AADC-GT-002, with confirmatory evidence pending from long-term follow-up. PTC Therapeutics has also received a Rare Disease Priority Review Voucher, which they plan to monetize.
PTC Therapeutics (NASDAQ: PTCT) ha ricevuto l'approvazione accelerata dalla FDA per KEBILIDI™, la prima terapia genica mai somministrata direttamente al cervello per il trattamento della deficienza di AADC. La terapia è approvata sia per i bambini che per gli adulti, indipendentemente dal livello di gravità della malattia.
KEBILIDI viene somministrato attraverso una neurochirurgia stereotattica al putamen del cervello, permettendo la sintesi di dopamina e il miglioramento progressivo dello sviluppo motorio. L'approvazione si basa sullo studio clinico in corso PTC-AADC-GT-002, con evidenze confermative in attesa da un follow-up a lungo termine. PTC Therapeutics ha anche ricevuto un Voucher di Revisione Prioritaria per Malattie Rare, che intendono monetizzare.
PTC Therapeutics (NASDAQ: PTCT) ha recibido la aprobación acelerada de la FDA para KEBILIDI™, la primera terapia génica administrada directamente al cerebro para tratar la deficiencia de AADC. La terapia está aprobada tanto para niños como para adultos, independientemente de la gravedad de la enfermedad.
KEBILIDI se administra a través de una neurocirugía estereotáctica al putamen del cerebro, permitiendo la síntesis de dopamina y la mejora progresiva del desarrollo motor. La aprobación se basa en el ensayo clínico en curso PTC-AADC-GT-002, con evidencia confirmatoria pendiente de un seguimiento a largo plazo. PTC Therapeutics también ha recibido un Voucher de Revisión Prioritaria para Enfermedades Raras, que planean monetizar.
PTC Therapeutics (NASDAQ: PTCT)는 KEBILIDI™에 대해 FDA의 가속 승인을 받았습니다. 이는 AADC 결핍증 치료를 위해 뇌에 직접 투여되는 최초의 유전자 요법입니다. 치료법은 모든 질병 중증도에 대해 아동과 성인 모두에게 승인되었습니다.
KEBILIDI는 뇌의 피각에 스테레오택틱 신경외과를 통해 시행되며, 이는 도파민 합성과 점진적인 운동 발달 향상을 가능하게 합니다. 이번 승인은 진행 중인 임상 시험 PTC-AADC-GT-002를 기반으로 하며, 장기 추적 조사로부터의 확인 증거가 남아있습니다. PTC Therapeutics는 희귀 질환 우선 검토 바우처도 수령했으며, 이를 수익화할 계획입니다.
PTC Therapeutics (NASDAQ: PTCT) a reçu l'approbation accélérée de la FDA pour KEBILIDI™, la première thérapie génique administrée directement au cerveau pour traiter le déficit en AADC. La thérapie est approuvée pour les enfants et les adultes, quels que soient les niveaux de gravité de la maladie.
KEBILIDI est administré par neurochirurgie stéréotaxique au putamen du cerveau, permettant la synthèse de dopamine et une amélioration progressive du développement moteur. L'approbation est basée sur l'essai clinique en cours PTC-AADC-GT-002, l'évidence confirmatoire étant attendue d'un suivi à long terme. PTC Therapeutics a également reçu un Bon de Révision Prioritaire pour Maladies Rares, qu'ils prévoient de monétiser.
PTC Therapeutics (NASDAQ: PTCT) hat von der FDA eine beschleunigte Zulassung für KEBILIDI™ erhalten, die erste Gentherapie, die direkt im Gehirn zur Behandlung von AADC-Mangel verabreicht wird. Die Therapie ist sowohl für Kinder als auch für Erwachsene in allen Schweregraden der Erkrankung zugelassen.
KEBILIDI wird durch stereotaktische Neurochirurgie in das Putamen des Gehirns verabreicht, was die Dopamin-Synthese und eine progressive Verbesserung der motorischen Entwicklung ermöglicht. Die Zulassung basiert auf der laufenden klinischen Studie PTC-AADC-GT-002, während die bestätigenden Beweise aus einer Langzeitnachverfolgung noch ausstehen. PTC Therapeutics hat außerdem einen Prioritätsgutschein für seltene Krankheiten erhalten, den sie monetarisieren möchten.
- First-ever FDA approved gene therapy for direct brain administration
- Broad label approval covering both children and adults
- Received valuable Priority Review Voucher that can be monetized
- Centers of excellence identified and surgeons already trained for launch
- Approval is accelerated and requires confirmatory evidence
- Treatment requires invasive brain surgery procedure
- market size due to rare disease indication
Insights
- First-ever FDA approval for gene therapy directly administered to the brain -
- Priority review voucher granted -
- Broad label including children and adults -
- PTC pioneers new approach for CNS drug delivery -
"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases," said Matthew B. Klein, M.D., Chief Executive Officer, 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 gene therapy, which will be marketed in
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. KEBILIDI is a gene replacement therapy that is directly administered to the putamen of the brain through a stereotactic neurosurgical procedure. Clinical trial results demonstrate that following gene therapy, de novo synthesis of dopamine occurs, followed by the progressive acquisition of motor development milestones.
KEBILIDI received accelerated approval based on the safety and clinical efficacy findings in the ongoing global clinical trial of the gene therapy (PTC-AADC-GT-002). Confirmatory evidence will be provided from the long-term follow up of patients already treated in the study.
Along with the Biologics License Application approval, a Rare Disease Priority Review Voucher was granted. The company plans to monetize the voucher.
About aromatic L-amino acid decarboxylase (AADC) deficiency
AADC deficiency is a fatal, rare genetic disorder that typically causes severe disability and suffering from the first months of life, affecting every aspect of life—physical, mental and behavioral.1-4 The suffering of children with AADC deficiency may be exacerbated by oculogyric crises, which are distressing, painful episodes that resemble seizures and are characterized by a stuck upward gaze, dystonia, and inconsolability.1-5
The lives of affected children are severely impacted and shortened.1 Ongoing physical, occupational and speech therapy, and interventions, including surgery, are also often required to manage potentially life-threatening complications, such as infections and severe feeding and breathing problems.1,6,7
About KEBILIDI™ (eladocagene exuparvovec-tneq)
KEBILIDI is a recombinant adeno-associated virus serotype 2 (rAAV2)-based gene therapy, containing the human DDC gene. It is designed to correct the underlying genetic defect by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production.
Administration of KEBILIDI occurs through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure used for the treatment of a number of pediatric and adult neurological disorders. The administration procedure is performed by a qualified neurosurgeon in centers specialized in stereotactic neurosurgery. KEBILIDI is authorized to be administered using the SmartFlow Neuro Cannula.
Indications and Important Safety Information
Indication
KEBILIDI is an adeno-associated virus vector-based gene therapy indicated for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. This indication is approved under accelerated approval based on change from baseline in gross motor milestone achievement at 48 weeks post-treatment. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
IMPORTANT SAFETY INFORMATION
Contraindications
KEBILIDI is contraindicated in patients who have not achieved skull maturity assessed by neuroimaging. Skull maturity is needed for stereotactic neurosurgical administration of KEBILIDI.
Warnings and Precautions
Procedure-Related Monitoring: Procedural complications have been reported after neurosurgery required for KEBILIDI administration. These events included respiratory and cardiac arrest which occurred within 24 hours of the neurosurgical procedure and during post-surgical care. KEBILIDI administration has the potential risk for additional procedure related adverse events including cerebrospinal fluid (CSF) leak, intracranial bleeding, neuroinflammation, acute infarction, and infection. Patients should be monitored for procedure related adverse events with KEBILIDI administration.
Dyskinesia: Dyskinesia was reported after administration of KEBILIDI. All events were reported within 3 months of administration and 2 events required hospitalization. Monitor patients for signs and symptoms of dyskinesia after KEBILIDI treatment which may include involuntary movements of face, arm, leg, or entire body. These may present as fidgeting, writhing, wriggling, head bobbing or body swaying. The use of dopamine antagonists may be considered to control dyskinesia symptoms.
Adverse Reactions
The most common adverse reactions (≥
Use in Specific Populations
- Pediatric Use: The safety and efficacy of KEBILIDI have not been studied in pediatric patients younger than 16 months.
- Geriatric Use: Clinical studies of KEBILIDI did not include patients 65 years of age and older.
You may also report adverse events directly to FDA at 1–800–FDA–1088 or www.fda.gov/medwatch. For product complaints or to report an adverse event, please call 1–866–562–4620 or email at usmedinfo@ptcbio.com.
For more additional information, please see the full Prescribing Information.
About PTC Therapeutics, Inc.
PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to children and adults living with rare disorders. PTC's ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC's mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC's strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. To learn more about PTC, please visit us at www.ptcbio.com and follow us on Facebook, Instagram, LinkedIn and X.
For More Information:
Investors:
Ellen Cavaleri
+1 (615) 618-6228
ecavaleri@ptcbio.com
Media:
Jeanine Clemente
+1 (908) 912-9406
jclemente@ptcbio.com
Forward-Looking Statement:
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, expectations with respect to KEBILIDI, including the timing of commercial availability; PTC's expectations with respect to the licensing, regulatory submissions and commercialization of its other products and product candidates; PTC's expectations with regards to its plans for the Rare Disease Priority Review Voucher; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions.
PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; expectations with respect to KEBILIDI and Upstaza, including potential commercialization, any regulatory submissions and potential approvals, manufacturing capabilities and the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors.
As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including KEBILIDI and Upstaza.
The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law.
References:
1. Wassenberg T, et al. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis. 2017;12(1):12.
2. Hwu WL et al. Natural History of Aromatic L -Amino Acid Decarboxylase Deficiency in
3. Himmelreich N et al. Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook. Mol Genet Metab. 2019;127:12–22
4. Chien YH, et al. Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1 /2 trial. Lancet Child Adolesc Health. 2017;1(4):265-273.
5. Pearson TS et al. AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients. J Inherit Metab Dis 2020;43:1121–30.
6. Chien YH, et al. 3-O-methyldopa levels in newborns: Result of newborn screening for aromatic L -amino-acid decarboxylase deficiency. Mol Genet Metab. August 2016;118(4):259-263.
7. Leuzzi, et al. Report of two never treated adult sisters with aromatic L-amino Acid decarboxylase deficiency: a portrait of the natural history of the disease or an expanding phenotype? JIMD Rep. 2015; 15: 39–45.
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SOURCE PTC Therapeutics, Inc.
FAQ
What is KEBILIDI and what did the FDA approve it for?
How is PTCT's KEBILIDI gene therapy administered?
What type of FDA approval did PTCT receive for KEBILIDI?
What additional benefit did PTCT receive with the KEBILIDI approval?
