Ultragenyx Completes Enrollment of Phase 3 Aspire Study Evaluating GTX-102 for the Treatment of Angelman Syndrome
Ultragenyx Pharmaceutical (NASDAQ: RARE) has completed enrollment for its Phase 3 Aspire study of GTX-102 (apazunersen) for Angelman Syndrome treatment. The study successfully enrolled 129 participants aged 4-17 with confirmed maternal UBE3A gene deletion in just seven months.
The trial design includes a 1:1 randomization between GTX-102 intrathecal injection and sham control, with active treatment consisting of three monthly 8 mg loading doses followed by maintenance doses up to 14 mg quarterly. The study's primary endpoint focuses on cognitive improvement measured by Bayley-4 cognitive raw score, with completion expected in second half of 2026.
Additionally, Ultragenyx plans to initiate the Aurora study of GTX-102 in additional ages and genotypes in the second half of 2025.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha completato il reclutamento per lo studio di Fase 3 Aspire su GTX-102 (apazunersen) per il trattamento della Sindrome di Angelman. Lo studio ha arruolato con successo 129 partecipanti di età compresa tra 4 e 17 anni con confermata delezione materna del gene UBE3A in soli sette mesi.
Il disegno dello studio prevede una randomizzazione 1:1 tra l'iniezione intratecale di GTX-102 e un controllo simulato, con il trattamento attivo che consiste in tre dosi di caricamento mensili da 8 mg, seguite da dosi di mantenimento fino a 14 mg ogni trimestre. Il parametro primario dello studio si concentra sul miglioramento cognitivo misurato dal punteggio grezzo cognitivo Bayley-4, con completamento previsto nella seconda metà del 2026.
Inoltre, Ultragenyx prevede di avviare lo studio Aurora su GTX-102 per fasce d'età e genotipi aggiuntivi nella seconda metà del 2025.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha completado la inscripción para su estudio de Fase 3 Aspire de GTX-102 (apazunersen) para el tratamiento del Síndrome de Angelman. El estudio logró inscribir con éxito a 129 participantes de entre 4 y 17 años con deleción confirmada del gen UBE3A materno en solo siete meses.
El diseño del ensayo incluye una aleatorización 1:1 entre la inyección intratecal de GTX-102 y un control simulado, con el tratamiento activo que consiste en tres dosis mensuales de carga de 8 mg seguidas de dosis de mantenimiento de hasta 14 mg trimestralmente. El objetivo principal del estudio se centra en la mejora cognitiva medida por la puntuación bruta cognitiva Bayley-4, con finalización prevista para la segunda mitad de 2026.
Además, Ultragenyx planea iniciar el estudio Aurora de GTX-102 en edades y genotipos adicionales en la segunda mitad de 2025.
Ultragenyx Pharmaceutical (NASDAQ: RARE)는 Angelman 증후군 치료를 위한 GTX-102 (apazunersen)의 3상 Aspire 연구 등록을 완료했습니다. 이 연구는 7개월 만에 모친 UBE3A 유전자 결실이 확인된 4세에서 17세 사이의 129명의 참가자를 성공적으로 등록했습니다.
임상시험 설계는 GTX-102 척수강 내 주사와 위약 대조군 간의 1:1 무작위 배정을 포함하며, 활성 치료는 3회의 월별 8mg 적재 용량과 이후 분기별 최대 14mg 유지 용량으로 구성됩니다. 연구의 주요 평가 변수는 Bayley-4 인지 원점수를 통한 인지 개선에 초점을 맞추며, 완료는 2026년 하반기로 예상됩니다.
추가로, Ultragenyx는 2025년 하반기에 추가 연령대 및 유전자형을 대상으로 GTX-102의 Aurora 연구를 시작할 계획입니다.
Ultragenyx Pharmaceutical (NASDAQ: RARE) a terminé le recrutement pour son étude de Phase 3 Aspire portant sur GTX-102 (apazunersen) pour le traitement du syndrome d'Angelman. L'étude a réussi à inclure 129 participants âgés de 4 à 17 ans présentant une délétion maternelle confirmée du gène UBE3A en seulement sept mois.
Le protocole de l'essai comprend une randomisation 1:1 entre une injection intrathécale de GTX-102 et un contrôle simulé, le traitement actif comprenant trois doses de charge mensuelles de 8 mg suivies de doses d'entretien jusqu'à 14 mg trimestriellement. Le critère principal de l'étude porte sur l'amélioration cognitive mesurée par le score brut cognitif Bayley-4, avec une fin prévue pour la seconde moitié de 2026.
De plus, Ultragenyx prévoit de lancer l'étude Aurora sur GTX-102 pour des âges et génotypes supplémentaires au second semestre 2025.
Ultragenyx Pharmaceutical (NASDAQ: RARE) hat die Einschreibung für seine Phase-3-Studie Aspire zu GTX-102 (apazunersen) zur Behandlung des Angelman-Syndroms abgeschlossen. Die Studie hat erfolgreich 129 Teilnehmer im Alter von 4 bis 17 Jahren mit bestätigter maternaler UBE3A-Gen-Deletion in nur sieben Monaten rekrutiert.
Das Studiendesign umfasst eine 1:1-Randomisierung zwischen intrathekaler GTX-102-Injektion und Scheinbehandlung, wobei die aktive Behandlung aus drei monatlichen 8-mg-Ladedosen gefolgt von Erhaltungsdosen von bis zu 14 mg vierteljährlich besteht. Der primäre Endpunkt der Studie konzentriert sich auf die kognitive Verbesserung, gemessen am kognitiven Rohwert des Bayley-4-Tests, mit einem Abschluss in der zweiten Hälfte des Jahres 2026.
Zusätzlich plant Ultragenyx, in der zweiten Hälfte des Jahres 2025 die Aurora-Studie zu GTX-102 bei weiteren Altersgruppen und Genotypen zu starten.
- Rapid enrollment completion in just 7 months demonstrates strong patient interest and urgent market need
- Promising preliminary results from Phase 1/2 study showing developmental gains
- Treatment targets the underlying genetic cause of Angelman syndrome, currently an untreated condition
- Long timeline to study completion (second half of 2026)
- Complex treatment administration requiring intrathecal injection via lumbar puncture
Insights
Ultragenyx's Phase 3 Angelman syndrome trial completes enrollment ahead of schedule, signaling strong demand for this potential first-in-class genetic treatment.
Ultragenyx has reached a significant clinical milestone with the completed enrollment of approximately 129 participants in its Phase 3 Aspire study for GTX-102 (apazunersen), targeting Angelman syndrome patients aged 4-17 with full maternal UBE3A gene deletion. The rapid enrollment—completed in just seven months rather than the typical 12-18 months for rare disease trials—indicates substantial unmet medical need and strong community support.
The trial design employs a 1:1 randomization to either active treatment or sham comparator, with a structured dosing regimen consisting of three monthly 8 mg loading doses followed by maintenance therapy escalating to 14 mg quarterly. The primary endpoint focuses on cognitive improvement measured via Bayley-4 cognitive raw score, while the key secondary endpoint utilizes a Multi-domain Responder Index across five functional domains.
This advancement follows encouraging preliminary results from the Phase 1/2 study, where patients demonstrated developmental gains. GTX-102's mechanism aims directly at the underlying genetic cause of Angelman syndrome, potentially restoring UBE3A protein function. With study completion expected in H2 2026 and the Aurora study expanding to additional patient populations on track to begin in H2 2025, Ultragenyx is positioning GTX-102 as potentially the first disease-modifying treatment for this condition with no current therapeutic options.
Company expects to complete Phase 3 Aspire study in the second half of 2026
Aurora study of GTX-102 in additional ages and genotypes on track to initiate in the second half of 2025
NOVATO, Calif., July 31, 2025 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that the Phase 3 Aspire study evaluating GTX-102 (apazunersen) as a treatment for Angelman Syndrome is fully enrolled, with approximately 129 participants ages four to 17 with a genetically confirmed diagnosis of full maternal UBE3A gene deletion.
“The accelerated enrollment of the Phase 3 Aspire study underscores the urgent need and strong desire for an effective treatment for these patients. Support from the Angelman syndrome community was critical to the achievement of this important milestone for GTX-102 with completion of enrollment in seven months. We are grateful to the study site teams, investigators, and families for their dedication and support,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “The continued developmental gains observed in the Phase 1/2 study provide a strong foundation as we advance this program with the potential to address the underlying genetic cause of this disease and enhance the quality of life for children living with Angelman syndrome.”
Jean-Baptiste Le Pichon, MD, PhD, FAAP, Interim Division Director, Neurology; Madison Lauren Sargent Endowed Professorship in Neurology/Angelman Syndrome, Children’s Mercy and an investigator on the Aspire study, added: “Today there are thousands of children and adults in the U.S. living with Angelman syndrome, with no cure or hope. To have a treatment in development with the potential to correct the underlying genetic error that forms the basis of Angelman syndrome, restore protein function, and recover function for patients is extremely meaningful. Completing enrollment of this study is a major milestone, and I eagerly look forward to additional data that builds on the promising preliminary results from the previous Phase 1/2 study.”
Enrollment in the global Phase 3 Aspire study (NCT06617429) began in December 2024. Participants are randomized 1:1 to receive GTX-102 by intrathecal injection via lumbar puncture or to the sham comparator group for a period of 48 weeks. 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. Participants in the sham comparator group will be eligible to cross over onto treatment after completing their Week 48 assessments. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score, and the key secondary endpoint (with a
About GTX-102 (apazunersen)
GTX-102 (apazunersen) is an investigational antisense oligonucleotide (ASO) therapy delivered via intrathecal administration and designed to target and inhibit expression of the 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 Breakthrough Therapy Designation, 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 ultra-rare 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, anticipated timing of data from ongoing GTX-102 studies, anticipated timing for initiation and completion of GTX-102 studies, 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 May 7, 2025, 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-/).
Ultragenyx Contacts
Investors
Joshua Higa
ir@ultragenyx.com
Media
Jess Rowlands
media@ultragenyx.com
FAQ
What is the status of Ultragenyx's (RARE) Phase 3 Aspire study for GTX-102?
How is GTX-102 administered in Ultragenyx's Angelman Syndrome trial?
What are the primary endpoints for Ultragenyx's GTX-102 Phase 3 trial?
How many patients are enrolled in Ultragenyx's Phase 3 GTX-102 trial?
When will Ultragenyx report results from the GTX-102 Phase 3 trial?
