Ultragenyx Announces First Patient Dosed in Pivotal Phase 3 Aspire Study Evaluating GTX-102 in Angelman Syndrome
Ultragenyx Pharmaceutical (NASDAQ: RARE) has initiated patient dosing in its pivotal Phase 3 Aspire study evaluating GTX-102 for Angelman syndrome. The global study will enroll approximately 120 children aged 4-17 with genetically confirmed maternal UBE3A gene deletion. Participants will be randomized 1:1 to receive GTX-102 or sham treatment over 48 weeks.
The treatment group will receive three monthly 8mg loading doses, followed by maintenance doses up to 14mg quarterly. The study's primary endpoint focuses on cognitive improvement measured by Bayley-4 cognitive raw score, with a key secondary endpoint using the Multi-domain Responder Index across cognition, communication, behavior, motor function, and sleep. The company plans to initiate the Aurora study in 2025 to evaluate GTX-102 in other Angelman syndrome genotypes and age groups.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha iniziato la somministrazione del trattamento ai pazienti nel suo studio clinico principale Phase 3 Aspire che valuta GTX-102 per la sindrome di Angelman. Lo studio globale recluterà circa 120 bambini di età compresa tra 4 e 17 anni con delezione genetica confermata del gene UBE3A materno. I partecipanti saranno randomizzati in un rapporto 1:1 per ricevere GTX-102 o un trattamento placebo per 48 settimane.
Il gruppo di trattamento riceverà tre dosi di carico mensili da 8mg, seguite da dosi di mantenimento fino a 14mg ogni tre mesi. L'endpoint primario dello studio si concentra sul miglioramento cognitivo misurato tramite il punteggio grezzo della Bayley-4, mentre un endpoint secondario chiave utilizza l'Indice di Risposta Multidimensionale in relazione a cognizione, comunicazione, comportamento, funzione motoria e sonno. L'azienda prevede di avviare lo studio Aurora nel 2025 per valutare GTX-102 in altri genotipi e fasce d'età della sindrome di Angelman.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha comenzado la dosificación de pacientes en su estudio pivotal Phase 3 Aspire que evalúa GTX-102 para el síndrome de Angelman. El estudio global inscribirá aproximadamente a 120 niños de 4 a 17 años con deleción genética confirmada del gen UBE3A materno. Los participantes serán aleatorizados 1:1 para recibir GTX-102 o tratamiento simulado durante 48 semanas.
El grupo de tratamiento recibirá tres dosis de carga mensuales de 8mg, seguidas de dosis de mantenimiento de hasta 14mg trimestralmente. El objetivo primario del estudio se centra en la mejora cognitiva medida a través del puntaje crudo de Bayley-4, mientras que un objetivo secundario clave utiliza el Índice de Respondedores Multidimensional en cognición, comunicación, comportamiento, función motora y sueño. La empresa planea iniciar el estudio Aurora en 2025 para evaluar GTX-102 en otros genotipos y grupos de edad del síndrome de Angelman.
Ultragenyx Pharmaceutical (NASDAQ: RARE)는 앤젤만 증후군을 위해 GTX-102를 평가하는 중요한 3상 Aspire 연구에서 환자 투약을 시작했습니다. 이 글로벌 연구는 유전자에 의해 확인된 어머니의 UBE3A 유전자 결실이 있는 4세에서 17세 사이의 약 120명 어린이를 등록할 것입니다. 참가자는 1:1로 무작위 배정되어 GTX-102 또는 위약 치료를 48주 동안 받을 예정입니다.
치료 그룹은 8mg 로딩 용량을 월 3회 투여받고, 이후 분기별로 최대 14mg의 유지 용량을 받게 됩니다. 연구의 주요 목표는 Bayley-4의 인지 원점수를 측정하여 인지적 개선에 초점을 맞추고 있으며, 주요 이차 목표는 인지, 의사소통, 행동, 운동 기능 및 수면 전반에 걸쳐 다영역 응답자 지수를 사용하는 것입니다. 이 회사는 2025년에 앤젤만 증후군의 다른 유전자형 및 연령대에서 GTX-102를 평가하기 위한 오로라(Aurora) 연구를 시작할 계획입니다.
Ultragenyx Pharmaceutical (NASDAQ: RARE) a lancé la distribution du traitement aux patients dans son étude pivot Phase 3 Aspire qui évalue GTX-102 pour le syndrome d'Angelman. L'étude mondiale recrutera environ 120 enfants âgés de 4 à 17 ans présentant une délétion génétique confirmée du gène UBE3A maternel. Les participants seront randomisés dans un rapport de 1:1 pour recevoir GTX-102 ou un traitement placebo pendant 48 semaines.
Le groupe traité recevra trois doses de chargement mensuelles de 8mg, suivies de doses d'entretien allant jusqu'à 14mg par trimestre. Le critère principal de l'étude se concentre sur l'amélioration cognitive mesurée par le score brut cognitif de Bayley-4, tandis qu'un critère secondaire clé utilise l'Indice Multi-dimensionnel des Répondeurs concernant la cognition, la communication, le comportement, la fonction motrice et le sommeil. L'entreprise prévoit de lancer l'étude Aurora en 2025 pour évaluer GTX-102 dans d'autres génotypes et groupes d'âge du syndrome d'Angelman.
Ultragenyx Pharmaceutical (NASDAQ: RARE) hat mit der Patientendosierung in seiner entscheidenden Phase 3 Aspire-Studie begonnen, die GTX-102 bei Angelman-Syndrom bewertet. Die globale Studie wird etwa 120 Kinder im Alter von 4 bis 17 Jahren mit genetisch bestätigtem mütterlichen UBE3A-Genverlust rekrutieren. Die Teilnehmer werden im Verhältnis 1:1 randomisiert, um GTX-102 oder eine Placebo-Behandlung über einen Zeitraum von 48 Wochen zu erhalten.
Die Behandlungsgruppe erhält drei monatliche Lade-Dosen von 8mg, gefolgt von Erhaltungsdosen von bis zu 14mg vierteljährlich. Der primäre Endpunkt der Studie konzentriert sich auf die kognitive Verbesserung, die durch den Rohwert der Bayley-4 gemessen wird, wobei ein wesentlicher sekundärer Endpunkt den Multi-Domain-Responder-Index in Bezug auf Kognition, Kommunikation, Verhalten, motorische Funktion und Schlaf verwendet. Das Unternehmen plant, 2025 die Aurora-Studie zu starten, um GTX-102 bei anderen Genotypen und Altersgruppen des Angelman-Syndroms zu bewerten.
- Advancement to Phase 3 clinical trials indicates promising development progress
- Large-scale study with 120 participants strengthens potential statistical significance
- Comprehensive trial design with both primary and secondary endpoints
- Planned expansion to additional patient populations through Aurora study in 2025
- Extended timeline with 48-week study period before primary efficacy analysis
- Complex treatment regimen requiring intrathecal injection via lumbar puncture
Insights
The initiation of the Phase 3 Aspire study for GTX-102 represents a important milestone in Ultragenyx's clinical development program. The 120-patient trial design demonstrates robust statistical power, with the 1:1 randomization and sham control group adding scientific rigor. The dosing strategy - three monthly 8mg loading doses followed by quarterly maintenance doses up to 14mg - builds upon Phase 1/2 data that validated this approach.
The selection of Bayley-4 cognitive raw score as the primary endpoint and the Multi-domain Responder Index as key secondary endpoint is strategically sound. These endpoints comprehensively evaluate the drug's impact across critical disease manifestations. The 48-week duration allows sufficient time to demonstrate meaningful clinical benefits in this complex neurodevelopmental disorder.
For simplified understanding: Think of GTX-102 as a precise molecular tool designed to turn back on a gene that's switched off in Angelman syndrome. The Phase 3 trial is like a large-scale test to prove this tool works consistently and safely across many patients.
This Phase 3 trial initiation strengthens Ultragenyx's position in the rare disease space, particularly in Angelman syndrome where there are currently no approved treatments. The market opportunity is significant - Angelman syndrome affects approximately 1 in 15,000 births, representing an underserved market with high unmet medical need.
The company's planned expansion into the Aurora study in 2025, targeting different genotypes and age groups, indicates a comprehensive commercial strategy to maximize GTX-102's market potential. Success in this pivotal trial could establish Ultragenyx as the leader in Angelman syndrome therapeutics, potentially capturing a substantial portion of this orphan drug market.
In simple terms: If successful, this drug could be the first approved treatment for Angelman syndrome, giving Ultragenyx exclusive access to a valuable market where patients currently have no therapeutic options.
Company on track to initiate the Aurora study to evaluate GTX-102 in other Angelman syndrome genotypes and in other age groups in 2025
NOVATO, Calif., Dec. 19, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), today announced that the first patient has been dosed in the pivotal Phase 3 Aspire study (NCT06617429) evaluating the efficacy and safety of GTX-102, its investigational antisense oligonucleotide (ASO) for Angelman syndrome.
"Initiation of patient dosing in our Phase 3 Aspire study represents an important step forward in the development of an effective, and much needed, treatment for patients and families affected by Angelman syndrome,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. "Our goal with Aspire is to confirm the safety and clinical efficacy of GTX-102 in a large, randomized trial with a population that represents the majority of patients with Angelman syndrome. Additionally, the Aurora study will further assess safety and validate efficacy in patients with different genotypes and in younger and older patients."
The global Phase 3 Aspire study will enroll approximately 120 children ages 4 to 17 with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. Participants will be randomized 1:1 to receive GTX-102 by intrathecal injection via lumbar puncture or to the sham comparator group during the 48-week primary efficacy analysis period. Participants in the active treatment group will receive three, monthly 8 mg loading doses of GTX-102 followed by dosing in a maintenance period that will increase to a maximum dose of 14 mg of GTX-102 quarterly. Patients in the sham comparator group will be eligible to crossover onto treatment after Week 48 is complete. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score, and the key secondary endpoint will be the Multi-domain Responder Index (MDRI) across the five domains of cognition, receptive communication, behavior, gross motor function, and sleep.
“Angelman syndrome affects cognitive and motor function, making walking, communicating, and performing many everyday tasks more difficult for individuals living with Angelman syndrome. As a united community, ASF and FAST work together to further awareness and treatment of Angelman syndrome and are excited by all the recent progress in research and drug development. The initiation of the Phase 3 Aspire study by Ultragenyx is a significant achievement and something the community should celebrate,” stated Amanda Moore, chief executive officer at the Angelman Syndrome Foundation (ASF) and Ryan Fischer, chief operating officer at Foundation for Angelman Syndrome Therapeutics (FAST), in a joint statement.
At the 2024 Foundation for Angelman Syndrome Therapeutics (FAST) Global Science Summit in November, the company presented data from the Phase 1/2 study that confirmed the Phase 3 Aspire study dosing strategy and that the study is amply powered to establish the efficacy of GTX-102 on the primary endpoint of change in cognition, as measured by Bayley-4, or the key secondary endpoint of MDRI at the Week 48 timepoint.
U.S. residents can learn more by visiting www.ultraclinicaltrials.com.
About GTX-102
GTX-102 is an investigational antisense oligonucleotide (ASO) therapy delivered via intrathecal administration and designed to target and inhibit expression of the UBE3A antisense transcript (UBE3A-AS) to prevent silencing of the paternally inherited allele of the UBE3A gene and reactivate expression of the deficient protein. GTX-102 has been granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA and Orphan Designation and PRIME designation from the EMA.
About Angelman Syndrome
Angelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. The maternal-specific inheritance pattern of Angelman syndrome is due to genomic imprinting of UBE3A in neurons of the central nervous system (CNS), a naturally occurring phenomenon in which the maternal UBE3A allele is expressed and the paternal UBE3A is not. Silencing of the paternal UBE3A allele is regulated by the UBE3A-AS, the intended target of GTX-102. In almost all cases of Angelman syndrome, the maternal UBE3A allele is either missing or mutated, resulting in limited to no protein expression. This condition is generally not inherited but instead occurs spontaneously. It is estimated to affect approximately 60,000 people in commercially accessible geographies.
Angelman syndrome is a lifelong neurodevelopmental disorder that causes cognitive impairment, motor impairment, balance issues and debilitating seizures. Some individuals with Angelman syndrome are unable to walk and most do not speak. Anxiety and disturbed sleep can be serious challenges in individuals with Angelman syndrome. Although individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently. Angelman syndrome is not a degenerative disorder, but the loss of the UBE3A protein expression in neurons results in abnormal communications between neurons. Angelman syndrome is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome; however, several symptoms of this disorder can be reversed in adult animal models of Angelman syndrome, suggesting that improvement of symptoms can potentially be achieved at any age.
About Ultragenyx
Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease.
The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
For more information on Ultragenyx, please visit the company's website at: www.ultragenyx.com.
Forward-Looking Statements and Use of Digital Media
Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, business plans and objectives for GTX-102, expectations regarding the tolerability and safety of GTX-102, and future clinical and regulatory developments for GTX-102 are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop GTX-102, the company’s ability to achieve its projected development goals in its expected timeframes, the risk that results from earlier studies may not be predictive of future study results, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements.
For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 6, 2024, and its subsequent periodic reports filed with the SEC.
In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).
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ir@ultragenyx.com
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