GeneTx Biotherapeutics LLC and Ultragenyx Pharmaceutical Inc.
(NASDAQ: RARE), companies partnered in the development of
intrathecally administered GTX-102, an investigational treatment
for Angelman syndrome, today announced that the U.K. Medicines and
Healthcare Products Regulatory Agency (MHRA) has approved the
Clinical Trial Application (CTA) for the Phase 1/2 study of GTX-102
in pediatric patients with Angelman syndrome in the U.K. The
companies previously received clearance to enroll patients in the
Phase 1/2 study in Canada. The first patients from these regions
are expected to be enrolled in the study early in the second half
of 2021, with clinical data from some patients in the study
expected before the end of the year.
Additionally, GeneTx and Ultragenyx recently met with the U.S.
Food and Drug Administration (FDA) and had a productive discussion
regarding the Phase 1/2 study. Based on the outcome of the meeting,
GeneTx will submit an amended protocol to FDA that addresses key
FDA issues.
“We’ve made significant progress on the regulatory front over
the past few weeks with the Phase 1/2 study cleared to begin
enrollment in two countries. Based on our recent discussions, we
are encouraged about our proposal to begin redosing patients in the
U.S. pending FDA agreement,” said Scott Stromatt, M.D., Chief
Medical Officer of GeneTx. “GTX-102 has demonstrated clinical
activity in the first five patients dosed in the study, and the
modified trial design approved by the MHRA and Health Canada
intends to explore the benefit of repeat doses at the lower end of
the dosing range previously tested in order to help mitigate the
risk for serious adverse events caused by localized
inflammation.”
Phase 1/2 study design in U.K. and Canada
The Phase 1/2, open-label, multiple-dose, dose-escalating study
evaluates the safety, tolerability, and plasma and cerebrospinal
fluid concentrations of GTX-102 in pediatric patients with Angelman
syndrome with a genetically confirmed diagnosis of full
maternal UBE3A gene deletion. Under the amended protocol
approved in the U.K. and Canada, approximately 12 patients will be
enrolled into two cohorts split by age: patients ages 4 to 7 years
will be enrolled into Cohort 4, and patients ages 8 to 17 years
will be enrolled into Cohort 5.
The starting doses in Cohorts 4 (<8 years old) and 5 (>8
years old) will be 3.3 and 5 mg, respectively. Patients will
receive 3 to 4 monthly doses, titrated individually through smaller
steps than the first three cohorts in the original study with dose
increases based on response and enhanced safety monitoring.
Patients will then move to a maintenance phase during which they
will receive GTX-102 every three months and continue to be
monitored for response and safety. In this phase, individual dose
titration may continue if the clinical response is not much
improved in at least 2 domains up to a maximum dose of 14 mg.
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, 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 typically 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 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 U.S. Food and Drug
Administration (FDA). In August 2019, GeneTx and Ultragenyx
announced a partnership to develop GTX-102, with Ultragenyx
receiving an exclusive option to acquire GeneTx.
About GeneTx Biotherapeutics
GeneTx Biotherapeutics LLC is a startup biotechnology company
singularly focused on developing and commercializing a safe and
effective antisense therapeutic for the treatment of Angelman
syndrome. GeneTx was launched by FAST, a patient advocacy
organization and the largest non-governmental funder of Angelman
syndrome research. GeneTx licensed the rights to antisense
technology intellectual property from the Texas A&M University
System in December 2017.
About Ultragenyx Pharmaceutical Inc.
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
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, anticipated
cost or expense reductions, the timing, progress and plans for its
clinical programs and clinical studies, future regulatory
interactions, and the components and timing of regulatory
submissions 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 effects from the
COVID-19 pandemic on the company’s clinical activities, business
and operating results, risks related to reliance on third party
partners to conduct certain activities on the company’s behalf,
uncertainty and potential delays related to clinical drug
development, 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 10Q filed with the
Securities and Exchange Commission on May 5, 2021, and its
subsequent periodic reports filed with the Securities and Exchange
Commission.
ContactsUltragenyx Pharmaceutical Inc.Investors
Joshua Higa415-660-0951
Media Carolyn Wang415-225-5050
GeneTxPaula Evans630-639-7271Paula.Evans@GeneTxBio.com
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