Ultragenyx's GTX-102: A Promising Treatment for Angelman Syndrome
Saturday, Nov 9, 2024 10:40 am ET
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) recently presented positive updates on its GTX-102 Angelman syndrome program at the 2024 Foundation for Angelman Syndrome Therapeutics (FAST) Global Science Summit. This article explores the significance of these updates and the potential investment opportunities in the rare disease therapeutics sector.
Angelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. It is characterized by cognitive impairment, motor impairment, balance issues, and debilitating seizures. Currently, there are no approved therapies for Angelman syndrome, making the development of effective treatments a high unmet medical need.
GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal administration and designed to target and inhibit expression of UBE3A-AS. Nonclinical studies have shown that GTX-102 reduces levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the central nervous system (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.
The Phase 1/2 data presented at FAST showed improvements across all domains, with patients demonstrating a mean change in Bayley-4 Cognition Growth Scale Value (GSV) score from baseline of +6.7 compared to the minimally important difference of +5. Using the Phase 3 primary endpoint of Bayley-4 Cognition Raw score, the mean change from baseline was +10.9. This suggests the Phase 3 study has greater than 95% power to detect a treatment effect, even if the response in the sham arm is up to three times higher than observed changes in available natural history data.
Week 48 (Day 338) data from 28 patients in Expansion Cohorts A&B were evaluated with the Phase 3 key secondary endpoint of MDRI and showed a total net response of +2.0 (p-value < 0.0001). The data demonstrate that approximately 80% (22 of 28 patients) of patients have achieved clinically meaningful net improvement in at least one domain.
These data confirm that the Phase 3 Aspire study is amply powered to establish the efficacy of GTX-102 on the primary endpoint of cognition or the key secondary endpoint of MDRI at the Week 48 timepoint. GTX-102 demonstrated a consistent and acceptable safety profile as of the data cutoff.
The global Phase 3 Aspire study will enroll approximately 120 patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score, and the key secondary endpoint will be the Multi-domain Responder Index (MDRI) across the five domains of cognition, receptive communication, behavior, gross motor function, and sleep.
Ultragenyx is on track to begin enrolling the Phase 3 Aspire study by the end of 2024, with a robust and experienced global network of sites that will enable accelerated study execution. The positive data presented at FAST, along with the company's strong track record in rare disease therapeutics, makes Ultragenyx an attractive investment opportunity in the rare disease therapeutics sector.
Investors seeking stable, income-focused investments should consider the rare disease therapeutics sector, which offers potential for significant growth and returns. Ultragenyx's GTX-102 program demonstrates the company's commitment to developing innovative treatments for rare diseases, making it an appealing investment option for those looking to capitalize on undervalued opportunities in the healthcare sector.
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