Ultragenyx Provides Update on Stage 1 Cohorts in Pivotal Phase 1/2/3 Cyprus2+ Study Evaluating UX701 Gene Therapy for the Treatment of Wilson Disease
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has reported promising results from the Phase 1/2/3 Cyprus2+ study of its UX701 gene therapy for Wilson Disease. The study has shown meaningful clinical activity and improvements in copper metabolism in Stage 1. Notably, six patients have completely tapered off standard-of-care treatment, with responses observed across all three dose cohorts.
The company plans to enroll an additional cohort in Stage 1 with a moderately increased dose and an optimized immunomodulation regimen to enhance the therapy's efficiency and efficacy. The goal is to have the majority of patients discontinue standard-of-care treatment before selecting a dose for the randomized placebo-controlled stage.
UX701 has been well-tolerated, with no unexpected related treatment emergent adverse events or significant immunologic safety issues reported. The study's design includes three stages, with the primary efficacy endpoints being change in 24-hour urinary copper concentration and percent reduction in standard-of-care medication by Week 52 of Stage 2.
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) ha riportato risultati promettenti dallo studio Fase 1/2/3 Cyprus2+ della sua terapia genica UX701 per la Malattia di Wilson. Lo studio ha mostrato un'attività clinica significativa e miglioramenti nel metabolismo del rame nella Fase 1. In particolare, sei pazienti hanno completamente interrotto il trattamento standard, con risposte osservate in tutti e tre i gruppi di dosaggio.
L'azienda prevede di arruolare un ulteriore gruppo nella Fase 1 con una dose moderatamente aumentata e un regime di immunomodulazione ottimizzato per migliorare l'efficienza e l'efficacia della terapia. L'obiettivo è che la maggior parte dei pazienti interrompa il trattamento standard prima di selezionare una dose per la fase controllata randomizzata con placebo.
UX701 è stata ben tollerata, senza eventi avversi emergenti correlati al trattamento inattesi o problemi significativi di sicurezza immunologica segnalati. Il disegno dello studio include tre fasi, con gli endpoint di efficacia primari che sono il cambiamento nella concentrazione di rame nelle urine nelle 24 ore e la percentuale di riduzione del farmaco standard entro la Settimana 52 della Fase 2.
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) ha reportado resultados prometedores del estudio de Fase 1/2/3 Cyprus2+ de su terapia génica UX701 para la Enfermedad de Wilson. El estudio ha mostrado una actividad clínica significativa y mejoras en el metabolismo del cobre en la Fase 1. Notablemente, seis pacientes han dejado completamente el tratamiento estándar, con respuestas observadas en los tres grupos de dosis.
La compañía planea inscribir un grupo adicional en la Fase 1 con una dosis moderadamente aumentada y un régimen de inmunomodulación optimizado para mejorar la eficiencia y eficacia de la terapia. El objetivo es que la mayoría de los pacientes dejen el tratamiento estándar antes de seleccionar una dosis para la fase aleatoria controlada con placebo.
UX701 ha sido bien tolerada, sin eventos adversos emergentes relacionados con el tratamiento inesperados ni problemas significativos de seguridad inmunológica reportados. El diseño del estudio incluye tres fases, con los puntos finales primarios de eficacia siendo el cambio en la concentración de cobre urinario de 24 horas y el porcentaje de reducción de la medicación estándar para la Semana 52 de la Fase 2.
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE)는 윌슨병에 대한 유전자 요법 UX701의 1/2/3상 Cyprus2+ 연구에서 유망한 결과를 보고했습니다. 이 연구는 1단계에서 의미 있는 임상 활동과 구리 대사의 개선을 나타냈습니다. 특히, 6명의 환자가 표준 치료를 완전히 중단했습니다, 세 가지 복용량 그룹 모두에서 반응이 관찰되었습니다.
회사는 적당히 증가된 용량과 최적화된 면역 조절 요법으로 치료의 효율성과 효과를 높이기 위해 1단계에서 추가 그룹을 모집할 계획입니다. 목표는 대부분의 환자가 무작위 이중 맹검 대조 시험 단계에서 용량을 선택하기 전에 표준 치료를 중단하는 것입니다.
UX701은 잘 견뎌졌습니다, 예상치 못한 관련 치료 발생 부작용이나 중요한 면역학적 안전성 문제가 보고되지 않았습니다. 연구 설계에는 세 단계가 포함되며, 주요 효능 종점은 2단계의 52주차까지 24시간 소변 내 구리 농도의 변화와 표준 약물의 백분율 감소입니다.
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) a rapporté des résultats prometteurs de l'étude de Phase 1/2/3 Cyprus2+ de sa thérapie génique UX701 pour la maladie de Wilson. L'étude a montré une activité clinique significative et des améliorations du métabolisme du cuivre au stade 1. Notamment, six patients ont complètement arrêté le traitement standard, avec des réponses observées dans les trois groupes de doses.
L'entreprise prévoit de recruter un groupe supplémentaire au stade 1 avec une dose modérément augmentée et un régime d'immunomodulation optimisé pour améliorer l'efficacité et l'efficience de la thérapie. L'objectif est que la majorité des patients interrompent le traitement standard avant de sélectionner une dose pour la phase regroupée contrôlée par placebo.
UX701 a été bien toléré, sans événements indésirables liés au traitement inattendus ni problèmes de sécurité immunologique significatifs rapportés. La conception de l'étude comprend trois phases, avec pour points d'efficacité principaux le changement de la concentration de cuivre dans les urines sur 24 heures et le pourcentage de réduction des médicaments standard d'ici la semaine 52 de la phase 2.
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) hat vielversprechende Ergebnisse aus der Phase 1/2/3-Studie Cyprus2+ seiner Gentherapie UX701 für Wilson-Krankheit berichtet. Die Studie zeigte eine bedeutende klinische Wirksamkeit und Verbesserungen im Kupferstoffwechsel in Phase 1. Bemerkenswerterweise haben sechs Patienten die Standardbehandlung vollständig abgesetzt, wobei in allen drei Dosierungsgruppen Reaktionen beobachtet wurden.
Das Unternehmen plant, eine weitere Kohorte in Phase 1 mit einer mäßig erhöhten Dosis und einem optimierten Immunmodulationsregime zu rekrutieren, um die Effizienz und Wirksamkeit der Therapie zu verbessern. Ziel ist es, dass die Mehrheit der Patienten die Standardbehandlung absetzt, bevor eine Dosis für die randomisierte placebokontrollierte Phase ausgewählt wird.
UX701 wurde gut toleriert, ohne unerwartete behandlungsbezogene Nebenwirkungen oder bedeutende immunologische Sicherheitsprobleme. Das Studiendesign umfasst drei Phasen, wobei die primären Wirksamkeitsendpunkte der Wechsel in der 24-Stunden-Kupferkonzentration im Urin und der prozentuale Rückgang der Standardmedikation bis zur Woche 52 von Phase 2 sind.
- Six patients have completely tapered off standard-of-care treatment
- Responses seen in all three dose cohorts
- Improvements in copper metabolism observed
- Non-ceruloplasmin bound copper (NCC) stabilized to normal levels in patients off standard-of-care
- Increases in ceruloplasmin-copper activity in some patients, consistent with improved ATP7b function
- UX701 has been well-tolerated with no unexpected related treatment emergent adverse events
- Additional cohort required at a higher dose, potentially delaying study progression
- Not all patients have been able to taper off standard-of-care treatment
Insights
The interim results from Ultragenyx's Phase 1/2/3 Cyprus2+ study for UX701 gene therapy in Wilson disease show promising clinical activity. Six out of 15 patients have completely tapered off standard-of-care treatment, with a seventh beginning to taper. This is a significant achievement, as it suggests the gene therapy may potentially replace current treatments.
Key findings include:
- Normalization of non-ceruloplasmin bound copper (NCC) levels in patients off standard care
- Increased ceruloplasmin-copper activity in some patients, indicating improved ATP7b function
- Good safety profile with no unexpected adverse events
The decision to add a fourth cohort with a higher dose and optimized immunomodulation regimen is strategic. It aims to enhance the therapy's efficacy and potentially increase the proportion of patients who can discontinue standard care. This could strengthen UX701's position as a transformative treatment for Wilson disease.
While these results are encouraging, investors should note that the study is still ongoing and final efficacy and safety data from the randomized Stage 2 will be important for regulatory approval and market potential.
This update on UX701 for Wilson disease is positive for Ultragenyx (RARE) and could significantly impact its future valuation. Key financial implications include:
- Market Potential: Wilson disease affects approximately 1 in 30,000 people worldwide. A successful gene therapy could capture a substantial portion of this market, potentially generating
hundreds of millions in annual revenue. - Competitive Advantage: If UX701 proves effective in eliminating the need for lifelong standard-of-care treatments, it could become the preferred option, strengthening Ultragenyx's market position.
- R&D Investment: The addition of a fourth cohort may increase short-term R&D expenses but could pay off by optimizing the therapy's efficacy and commercial potential.
- Timeline to Market: The study's adaptive design allows for faster progression to later stages, potentially accelerating the path to commercialization.
Investors should monitor the progress of the Cyprus2+ study closely, as positive final results could be a significant catalyst for RARE's stock price. However, it's important to note that gene therapy development carries inherent risks and uncertainties.
NOVATO, Calif., Oct. 03, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today reported that the Phase 1/2/3 Cyprus2+ study of its UX701 gene therapy has demonstrated meaningful clinical activity as well as improvements in copper metabolism in Stage 1. Multiple responders have completely tapered off of standard-of-care treatment with responses seen in all three dose cohorts. The company plans to enroll an additional cohort in Stage 1 at a moderately increased dose and with an optimized immunomodulation regimen to enhance the efficiency and efficacy of the gene therapy, with the objective of having the majority of patients come off of standard-of-care treatment before selecting a dose for the randomized placebo-controlled stage of the study.
In Stage 1, 15 patients were enrolled into three sequential dosing cohorts and followed for at least 24 weeks. Six of the patients have completely tapered off of standard-of-care treatment with chelators and/or zinc therapy, and a seventh patient has begun to taper as of the data cut-off date in August. In patients who have tapered off standard-of-care, non-ceruloplasmin bound copper (NCC) has stabilized to normal, healthy levels. In some patients, there were increases in ceruloplasmin-copper activity consistent with improved ATP7b function. From a safety perspective, UX701 has been well tolerated, with no unexpected related treatment emergent adverse events and no significant immunologic safety events as of the data cut-off. The company will be submitting a protocol amendment for the additional cohort at a moderately increased dose and with an optimized immunomodulation regimen to optimize delivery efficiency and efficacy for the AAV vector.
“We are encouraged by the clinical activity we’re seeing with UX701 at this interim timepoint, with clear signals of transgene expression and improved trafficking of copper in a subset of patients currently enrolled in the study. These results, in addition to a number of patients tapering off of standard-of-care, give us confidence that this could ultimately be a novel therapy for people living with Wilson disease,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “A higher dose and optimized immunomodulation should enhance the clinical effect of this gene therapy and the ability to remove current standard-of-care in an even broader set of patients.”
U.S. residents can learn more by visiting www.ultraclinicaltrials.com.
Phase 1/2/3 Cyprus2+ Study Design
This study evaluating UX701 for the potential treatment of Wilson disease is designed with three stages. During the first stage (Stage 1), the safety and efficacy of multiple dose levels of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2. To date, 15 patients have been enrolled into three sequential dosing cohorts to evaluate doses of 5.0 x 10^12 GC/kg, 1.0 x 10^13 GC/kg, and 2.0 x 10^13 GC/kg. A fourth dosing cohort will be added and all patients in Stage 1 will be evaluated over the course of 52 weeks.
In Stage 2, a new cohort of patients will be randomized 2:1 to receive the selected dose of UX701 or placebo. The primary safety and efficacy analyses will be conducted at Week 52 of Stage 2. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard-of-care medication by Week 52. After the initial 52-week study period, all patients will have long-term follow up in Stage 3.
About Wilson Disease
Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper. Loss of function of this copper-binding protein results in the accumulation of copper in the liver and other tissues, most notably the central nervous system, and failure to properly distribute copper by ceruloplasmin. Patients with Wilson disease experience hepatic, neurologic and/or psychiatric problems. Those with liver disease can experience such symptoms as fatigue, lack of appetite, abdominal pain and jaundice, and can progress to fibrosis, cirrhosis, life-threatening liver failure and death. Wilson disease can be treated by reducing copper absorption or removing excess copper from the body using life-long chelation therapy, but unmet needs exist because some treated patients experience clinical deterioration and severe side effects. Wilson disease affects more than 50,000 people in commercially accessible geographies.
About UX701
UX701 is an investigational AAV9 gene therapy designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion. It has been shown in preclinical studies to normalize copper trafficking and excretion from the body. UX701 has been granted Orphan Drug Designation in the United States and European Union and Fast Track Designation in the United States.
About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, 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.
Ultragenyx 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 UX701, expectations regarding the tolerability and safety of UX701, and future clinical and regulatory developments for UX701 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 UX701, the company’s ability to achieve its projected development goals in its expected timeframes, 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 August 2, 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-/).
Contacts
Ultragenyx Pharmaceutical Inc.
Investors
Joshua Higa
+1-415-475-6370
ir@ultragenyx.com
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