Ultragenyx Pharmaceutical Inc. Receives FDA Breakthrough Therapy Designation for GTX-102 to Treat Angelman Syndrome

Ultragenyx receives FDA Breakthrough Therapy Designation for GTX-102 to treat Angelman syndrome, with Phase 3 study enrollment ongoing.

Quiver AI Summary

Ultragenyx Pharmaceutical Inc. announced that it has received Breakthrough Therapy Designation from the FDA for GTX-102, an investigational treatment for Angelman syndrome. The designation highlights the urgent need for effective therapies for this condition and is based on positive preliminary clinical data. Enrollment for the Phase 3 Aspire study, aimed at around 120 children with a specific genetic form of Angelman syndrome, is progressing well and set to complete by 2025. Additionally, the Aurora study will assess GTX-102 in varying genotypes and ages of patients, expected to start later this year. Angelman syndrome is a neurogenetic disorder that leads to severe developmental challenges, and there are currently no approved treatments. Ultragenyx focuses on developing therapies for rare genetic diseases, and GTX-102 has already received multiple designations for expedited development.

Potential Positives

Ultragenyx has received Breakthrough Therapy Designation from the FDA for GTX-102, indicating significant potential therapeutic benefits for patients with Angelman syndrome.
The Phase 3 Aspire study for GTX-102 is rapidly enrolling, demonstrating strong progress and commitment to bringing the treatment to patients as quickly as possible.
Preliminary clinical evidence from the Phase 1/2 study shows positive developmental gains in patients, reinforcing the promise of GTX-102 in addressing the needs of those affected by Angelman syndrome.
The initiation of the Aurora study to evaluate GTX-102 in other genotypes and ages expands the potential impact of the treatment across a broader patient population.

Potential Negatives

The press release notes substantial risks and uncertainties associated with clinical drug development and obtaining regulatory approvals, potentially indicating significant challenges ahead for GTX-102.
Concerns are raised over the unpredictability and lengthy timeline of clinical development, which may hinder the company's ability to meet projected development goals.
There is no mention of partnerships or collaborations, which may suggest a lack of support or resources to navigate the complex drug development landscape.

FAQ

What is the FDA Breakthrough Therapy Designation for GTX-102?

The FDA granted Breakthrough Therapy Designation to GTX-102 to expedite its development for Angelman syndrome treatment.

When will the Phase 3 Aspire study be completed?

The Phase 3 Aspire study is on track to complete enrollment by 2025.

What are the eligibility criteria for the Aspire study?

Participants must be children ages four to 17 with a genetically confirmed full maternal UBE3A gene deletion.

What is the purpose of the Aurora study?

The Aurora study aims to evaluate GTX-102 in additional Angelman syndrome genotypes and age groups.

How many people are estimated to be affected by Angelman syndrome?

Angelman syndrome is estimated to affect around 60,000 people in commercially accessible geographies.

Disclaimer: This is an AI-generated summary of a press release distributed by GlobeNewswire. The model used to summarize this release may make mistakes. See the full release here.

$RARE Insider Trading Activity

$RARE insiders have traded $RARE stock on the open market 15 times in the past 6 months. Of those trades, 0 have been purchases and 15 have been sales.

Here’s a breakdown of recent trading of $RARE stock by insiders over the last 6 months:

EMIL D KAKKIS (President & CEO) has made 0 purchases and 3 sales selling 110,161 shares for an estimated $4,648,802.
KARAH HERDMAN PARSCHAUER (EVP and Chief Legal Officer) has made 0 purchases and 3 sales selling 15,836 shares for an estimated $669,040.
ERIK HARRIS (EVP & Chief Commercial Officer) sold 15,103 shares for an estimated $635,836
JOHN RICHARD PINION (See Remarks) sold 14,439 shares for an estimated $607,881
ERIC CROMBEZ (EVP and Chief Medical Officer) has made 0 purchases and 3 sales selling 9,707 shares for an estimated $405,485.
THOMAS RICHARD KASSBERG (CBO & EVP) sold 6,028 shares for an estimated $253,778
CORAZON (CORSEE) D. SANDERS sold 2,405 shares for an estimated $89,922
HOWARD HORN (Chief Financial Officer) sold 1,785 shares for an estimated $72,114
THEODORE ALAN HUIZENGA (SVP, Chief Accounting Officer) sold 967 shares for an estimated $40,710

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$RARE Hedge Fund Activity

We have seen 156 institutional investors add shares of $RARE stock to their portfolio, and 178 decrease their positions in their most recent quarter.

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VESTAL POINT CAPITAL, LP removed 1,000,000 shares (-66.7%) from their portfolio in Q1 2025, for an estimated $36,210,000
ADAGE CAPITAL PARTNERS GP, L.L.C. added 965,919 shares (+81.6%) to their portfolio in Q1 2025, for an estimated $34,975,926
SUVRETTA CAPITAL MANAGEMENT, LLC added 873,186 shares (+75.8%) to their portfolio in Q1 2025, for an estimated $31,618,065
MARSHALL WACE, LLP removed 717,495 shares (-68.2%) from their portfolio in Q1 2025, for an estimated $25,980,493
PRICE T ROWE ASSOCIATES INC /MD/ added 706,519 shares (+28.1%) to their portfolio in Q1 2025, for an estimated $25,583,052
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$RARE Analyst Ratings

Wall Street analysts have issued reports on $RARE in the last several months. We have seen 2 firms issue buy ratings on the stock, and 0 firms issue sell ratings.

Here are some recent analyst ratings:

William Blair issued a "Outperform" rating on 05/28/2025
Citigroup issued a "Buy" rating on 05/07/2025

To track analyst ratings and price targets for $RARE, check out Quiver Quantitative's $RARE forecast page.

$RARE Price Targets

Multiple analysts have issued price targets for $RARE recently. We have seen 2 analysts offer price targets for $RARE in the last 6 months, with a median target of $89.5.

Here are some recent targets:

An analyst from Piper Sandler set a target price of $115.0 on 03/17/2025
An analyst from Morgan Stanley set a target price of $64.0 on 03/07/2025

Full Release

Phase 3 Aspire study enrollment on track to complete in 2025

Aurora study to evaluate GTX-102 in other Angelman syndrome genotypes and ages expected to initiate later this year

NOVATO, Calif., June 27, 2025 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), today announced that it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for GTX-102 (apazunersen) as a treatment for Angelman syndrome.

"FDA Breakthrough Therapy Designation underscores both the urgent need for an effective treatment for patients and families affected by Angelman syndrome and the clinically meaningful results demonstrated to date with GTX-102,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. "Based on the strength of the Phase 2 data and with strong support and interest from the Angelman syndrome community, our Phase 3 Aspire study is rapidly enrolling across our global sites. We look forward to advancing GTX-102 through the development process as rapidly as possible to bring this potential treatment to patients.”

The FDA’s decision is based on preliminary clinical evidence including positive data from the Phase 1/2 study in 74 patients (4-17 years of age) with a full maternal UBE3A gene deletion, that showed participants have made consistent developmental gains with rapid, sustained and continuing improvements across multiple symptom domains when treated for up to 3 years. Breakthrough Therapy Designation aims to expedite the development and review of drugs that are intended to treat serious or life-threatening diseases and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing therapies.

Enrollment in the global Phase 3 Aspire study ( NCT06617429 ) began in December 2024 and is expected to enroll approximately 120 children ages four to 17 with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The Aurora study will evaluate GTX-102 across other Angelman syndrome genotypes and ages and is expected to initiate in the second half of 2025. Families can learn more by visiting www.ultraclinicaltrials.com .

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 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 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, 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
+1-415-475-6370
[email protected]

Media
Joey Fleury
[email protected]