Ultragenyx Announces Phase 3 Aspire results in Angelman Syndrome
Phase 3 Aspire failure prompts Ultragenyx to reconsider apazunersen and pursue significant cost reductions while leaning on its commercial portfolio.
Rhea-AI Summary
Ultragenyx (RARE) reported topline results from the Phase 3 Aspire trial of apazunersen (GTX-102) in Angelman syndrome, which did not meet its primary endpoint of change from baseline in Bayley-4 cognitive raw score or the key secondary endpoint of net response in the Multidomain Responder Index (MDRI).
The randomized groups were comparable at baseline and no efficacy differences were observed between treated and control groups on Bayley cognition scores or MDRI, including the five individual MDRI components. The safety profile in Aspire was consistent with the earlier Phase 1/2 program. Ultragenyx plans to evaluate the future of the apazunersen program and will reassess its planned operations to implement significant expense reductions while continuing to support its growing commercial business, including the recently approved GENGLYCOS for glycogen storage disease type Ia and the potential approval of UX111 for Sanfillipo syndrome, with a stated goal of achieving profitability in 2027.
Positive
- Phase 3 Aspire safety profile consistent with earlier Phase 1/2 data
- Growing commercial business highlighted as creating new revenue sources
- Recent approval of GENGLYCOS for glycogen storage disease type Ia
- Potential future approval of UX111 for Sanfillipo syndrome noted
- Company reiterates goal of profitability in 2027
Negative
- Phase 3 Aspire did not meet primary Bayley-4 cognition endpoint
- Key secondary MDRI net response endpoint also not achieved
- No efficacy differences seen between treated and control groups on Bayley or MDRI
- Company will consider discontinuation or major change to apazunersen program
- Planned operations review to implement significant expense reductions
Market reaction after Phase 3 clinical data: RARE -45.64%
Following this news, RARE has declined 45.64%, reflecting a significant negative market reaction. Our momentum scanner has triggered 24 alerts so far, indicating elevated trading interest and price volatility. The stock is currently trading at $14.42.
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Key Figures
Previous Clinical trial Reports
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Apr 02 | FDA filing acceptance | Positive | +4.8% | FDA accepted UX111 BLA resubmission and set a September 19, 2026 action date |
| Mar 12 | Phase 3 clinical data | Positive | -2.3% | DTX301 reduced plasma ammonia versus placebo with statistical significance at 36 weeks |
| Feb 23 | FDA filing acceptance | Positive | -0.9% | FDA accepted DTX401 BLA and granted Priority Review for GSDIa |
| Jan 23 | Phase 3 endpoint failure | Negative | +3.5% | Orbit and Cosmic failed primary fracture-rate endpoints versus respective comparators |
| Dec 29 | Phase 3 clinical data | Negative | -42.3% | Orbit and Cosmic missed fracture-rate endpoints despite improved bone mineral density |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Tag-specific clinical-trial news produced mixed reactions, with 3 divergences and 2 alignments; the average move was -7.44%.
Key Terms
antisense oligonucleotide medical
intrathecal administration medical
genomic imprinting medical
breakthrough therapy designation regulatory
orphan drug designation regulatory
AI-generated analysis. How Rhea-AI works. Not financial advice.
Phase 3 Aspire did not achieve the primary endpoint of change from Baseline in Bayley-4 cognitive raw score nor the key secondary endpoint of net response in Multidomain Responder Index (MDRI)
NOVATO, Calif., Sept. 02, 2026 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced results from the Phase 3 Aspire study for apazunersen (GTX-102) in Angelman syndrome. The study did not achieve the primary endpoint of change from Baseline in Bayley-4 cognitive raw score nor the key secondary endpoint of net response in Multidomain Responder Index (MDRI). The safety profile observed in Aspire was consistent with Phase 1/2.
“Based on everything we observed in the robust Phase 1/2 clinical development program and long-term extension study, we are disappointed by the Aspire result,” said Emil Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “Even more, we are disappointed for the global patient community who has invested so much in early-stage research, working to bring a first-ever treatment to their children.”
In Aspire, the randomized groups were comparable at baseline and consistent with the patients studied in Phase 2. There were no differences between the treated and control groups that could support efficacy in the Bayley Cognition raw scores nor in the MDRI when looking at net response or mean changes of the individual five endpoints included in the MDRI.
The Company will evaluate the apazunersen program in light of this outcome and make a decision on its disposition. The Company will also assess its planned operations to define and implement significant expense reductions, while supporting its growing commercial business.
Dr. Kakkis continued: “We will maintain focus on our growing commercial business, which continues to create meaningful value, including new sources of revenue from the recent approval of GENGLYCOS for glycogen storage disease type Ia, the potential approval of UX111 for Sanfillipo syndrome, and the expansion of existing products to new territories. This strong commercial foundation will support our pipeline, while continuing toward profitability in 2027.”
About apazunersen (GTX-102)
Apazunersen (GTX-102) 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. Apazunersen 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 apazunersen. 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 products to patients for the treatment of serious rare and ultra-rare 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.
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 plans to evaluate its operations and implement significant expense reductions, the Company’s expectations for profitability in 2027, the expected scope, timing, benefits and impact of those actions, its future operating results and financial performance, its business plans and objectives for GTX-102 following the Aspire results, the future development and regulatory path for GTX-102, the growth and importance of its commercial business, and the potential approval and commercialization of UX111 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 company’s ability to accurately analyze and interpret the Aspire results and determine an appropriate path forward for GTX-102, the uncertainty of clinical drug development and the unpredictability and lengthy process for obtaining regulatory approvals, the risk that results from earlier studies may not be predictive of future study results, the company’s ability to define and implement expense reductions and realize anticipated savings and benefits, the risk that expense reductions may disrupt the company’s operations, adversely affect its workforce or impair its ability to execute its business plans, 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 the 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 5, 2026 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 did Ultragenyx (RARE) announce about the Phase 3 Aspire trial in Angelman syndrome?
Ultragenyx announced that the Phase 3 Aspire trial of apazunersen (GTX-102) in Angelman syndrome did not achieve its primary endpoint on Bayley-4 cognitive raw score or the key secondary endpoint of net response in the Multidomain Responder Index (MDRI).
Did apazunersen (GTX-102) show efficacy in the Aspire Phase 3 study for Angelman syndrome?
No. There were no differences between treated and control groups that could support efficacy, either in Bayley Cognition raw scores or in MDRI net response and the mean changes of the five individual MDRI endpoints.
What was the safety outcome in Ultragenyx’s Phase 3 Aspire trial of apazunersen?
The safety profile observed in the Phase 3 Aspire trial was consistent with the Phase 1/2 clinical program and the long-term extension, indicating no new safety signals were highlighted in this announcement.
How will the Aspire Phase 3 results affect Ultragenyx’s apazunersen (GTX-102) program?
Ultragenyx stated it will evaluate the apazunersen program in light of the Aspire outcome and make a decision on its disposition, which could include changes or potential discontinuation.
What operational changes is Ultragenyx (RARE) planning after the Aspire trial results?
The company plans to assess its planned operations and define and implement significant expense reductions, while continuing to support its growing commercial business and product portfolio.
Which commercial and pipeline products did Ultragenyx highlight alongside the Aspire results?
Ultragenyx highlighted new revenue from the recent approval of GENGLYCOS for glycogen storage disease type Ia, the potential approval of UX111 for Sanfillipo syndrome, and expansion of existing products into new territories.
What financial outlook did Ultragenyx mention in connection with the Aspire trial update?
The company said its growing commercial foundation will support the pipeline and that it is continuing toward profitability in 2027, despite the negative Aspire Phase 3 outcome.