Ultragenyx Announces Completion of Enrollment in Global Phase 1/2 Trial of GTX-102 in Pediatric Patients with Angelman Syndrome
- Completion of patient enrollment in the Phase 1/2 trial is a positive development indicating progress in the development of novel therapies for rare and ultrarare genetic diseases.
- Interim data from the extension cohorts showed improvements across multiple domains compared to natural history data, indicating potential efficacy of GTX-102.
- The PR does not provide specific financial or market data to evaluate the impact of the trial on the company's financial performance.
Insights
The completion of patient enrollment in the Phase 1/2 clinical trial of GTX-102 by Ultragenyx Pharmaceutical Inc. represents a significant milestone in the development pipeline for treatments targeting rare genetic disorders such as Angelman syndrome (AS). The enrollment of a substantial number of patients, 74 globally, provides a robust sample size for evaluating the safety and efficacy of the antisense oligonucleotide GTX-102, which is administered intrathecally to inhibit UBE3A antisense transcript expression.
Antisense oligonucleotides are a class of therapeutic agents that modulate gene expression by binding to specific RNA sequences, thereby offering a targeted approach to treat genetic diseases. In the context of AS, which is characterized by severe neurological symptoms, the ability to regulate UBE3A-AS could potentially reverse or mitigate the developmental and neurological deficits associated with the condition.
The interim data suggesting improvements across multiple domains and the association with quantitative EEG changes indicate a promising therapeutic effect. However, the long-term safety profile will be critical, especially given the previous concerns over treatment-related adverse events such as lower extremity weakness. The absence of additional serious adverse events (SAEs) since November 2022 is reassuring, but continuous monitoring is essential.
For investors, the progress of Ultragenyx's GTX-102 through clinical trials is a critical factor influencing the company's valuation and stock performance. The successful completion of patient enrollment and the anticipation of data from dose expansion cohorts in the first half of 2024 can be seen as positive indicators of the company's operational efficiency and potential for future revenue streams, should the therapy receive regulatory approval.
It is important to note that the biopharmaceutical sector is highly volatile and sensitive to clinical trial outcomes. Positive results can lead to significant stock appreciation, while negative outcomes can have the opposite effect. The interim data showing improvements in patients is likely to be viewed favorably by the market, but the true impact on Ultragenyx's financials will hinge on the comprehensive data set expected in 2024, regulatory approval processes and the ability to commercialize GTX-102 effectively.
Moreover, the niche market of rare and ultrarare genetic diseases, while potentially lucrative due to the lack of treatment options and associated pricing power, also comes with high research and development costs and a smaller patient population. The long-term financial implications for Ultragenyx will depend on the balance between these factors and the ultimate clinical success of GTX-102.
The development of treatments for rare diseases such as Angelman syndrome has broader economic implications beyond the immediate business impact for Ultragenyx Pharmaceutical Inc. The healthcare system can benefit from the introduction of effective therapies by potentially reducing long-term care costs and improving the quality of life for patients, which in turn can lead to increased productivity and reduced societal costs.
However, the cost-effectiveness of such treatments is often debated due to high research and development expenses, leading to high prices for the end product. For GTX-102, the economic assessment will eventually need to consider the balance between the cost of therapy and the overall health and economic benefits derived from its use.
Additionally, advancements in treating rare genetic disorders can stimulate further research and innovation within the biopharmaceutical industry, potentially leading to breakthroughs in other areas of medicine. The success of GTX-102 could serve as a catalyst for investment in similar therapeutic approaches, with long-term positive effects on the sector's growth and sustainability.
Data from at least 20 patients enrolled in dose expansion cohorts anticipated in the first half of 2024
NOVATO, Calif., Jan. 03, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today announced the completion of patient enrollment in its Phase 1/2 clinical trial of GTX-102 for the treatment of pediatric patients with Angelman syndrome (AS). The dose-expansion cohorts (Cohorts A-E) have enrolled 53 patients for a total of 74 patients enrolled globally in the Phase 1/2 trial. GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal administration and is designed to target and inhibit expression of UBE3A antisense transcript (UBE3A-AS).
“With completion of enrollment in the Phase 1/2 trial, we remain on track to report results in the first half of 2024 from at least 20 expansion cohort patients on therapy for a minimum of 6 months. We are confident that the cumulative safety and efficacy data will allow for dose and endpoint selection to support our Phase 3 program,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We appreciate the support of the Angelman community, including the patients, families and healthcare providers, as we urgently work together to develop a new treatment option that may be able to improve the quality of life of those impacted by this devastating disease.”
In October 2023, interim data from the extension cohorts (Cohorts 4-7) of the ongoing Phase 1/2 study were announced and showed improvements across multiple domains compared to natural history data, where available, and clinical changes were associated with quantitative changes in EEG. Long-term data showed patients who stopped and restarted treatment reacquired previously gained developmental skills when they were re-dosed with the current regimen. As of the data cut-off, there have been no additional treatment-related SAEs, including lower extremity weakness, since November 2022.
About the Phase 1/2 study
The Phase 1/2, open-label, multiple-dose, dose-escalating study is evaluating the safety and tolerability of GTX-102 administered by intrathecal (IT) injection to pediatric patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The study is also assessing clinical response as measured by a panel of efficacy assessments for the functional domains impacted in Angelman syndrome. Patients in the earlier extension cohorts (Cohorts 4-7) of the study have moved into long-term maintenance dosing, and the study has completed enrollment for the new expansion cohorts to verify the GTX-102 dose range and treatment regimen that will be used in the Phase 3 program.
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 antisense transcript (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 1 in 12,000 to 1 in 20,000 people globally.
Individuals with Angelman syndrome have developmental delay, balance issues, motor impairment, 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. While 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 GTX-102
GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal administration and designed to target and inhibit expression of UBE3A-AS. Nonclinical studies show that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS. Reactivation of paternal UBE3A expression in animal models of Angelman syndrome has been associated with improvements in some of the neurological symptoms associated with the condition. GTX-102 has been granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA.
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, future clinical and regulatory developments for GTX-102, the clinical benefit, tolerability and safety of GTX-102, timing for enrollment, dosing and data for GTX-102 and the company’s other investigational therapies and regulatory meetings 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, risks related to adverse side effects, risks related to reliance on third-party partners to conduct certain activities on the company’s behalf, the potential for any license or collaboration agreement, 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 product 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 3, 2023, 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
415-475-6370
ir@ultragenyx.com
Media
Carolyn Wang
415-225-5050
media@ultragenyx.com
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