Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical
company focused on the development of novel products for rare and
ultra-rare diseases, today announced topline data from the Phase 2
study of UX007 in glucose transporter type-1 deficiency syndrome
(Glut1 DS) patients with seizures. The study did not meet the
primary endpoint of reducing the frequency of total number of
observable and absence seizures among patients treated from
baseline to Week 8 with UX007 compared to placebo. When evaluating
each seizure type independently, treatment with UX007 did show a
reduction in absence seizures captured on EEG, but not observable
seizures captured by diary.
“These data suggest that UX007 has a clinically meaningful
effect in Glut1DS patients with absence seizures,” said Emil D.
Kakkis, M.D., Ph.D., Chief Executive Officer and President of
Ultragenyx. “We look forward to studying UX007 in our Phase 3 study
in Glut1 DS patients with movement disorders, and continue to
evaluate our plans in the seizure indication.”
Efficacy Results
UX007 did not meet the primary endpoint of the study during the
eight-week placebo-controlled treatment period when evaluating
observable and absence seizures together. Patients treated with
UX007 (n=25) demonstrated a reduction of 13.4% in overall seizure
frequency (p=0.41) relative to placebo (n=11).
For the pre-specified secondary analysis of the primary
endpoint, patients with absence seizures (n=19) demonstrated a
47.3% reduction (p=0.009) in seizure frequency after eight weeks of
treatment with UX007, compared to baseline. While clinically
significant, this did not meet the statistical significance
threshold of 0.005 using the pre-defined multiplicity adjustment.
Patients with observable seizures (n=17) demonstrated a 9.1%
reduction (p=0.29) in seizure frequency following treatment.
Among UX007 treated patients with any absence seizures (with or
without observable seizures; n=19), 42% were responders (50% or
greater reduction in seizure frequency). Of those with absence
seizures on EEG at baseline (n=10), 80% were responders. Of
the patients who had absence seizures as determined by EEG (without
observable seizures; n=8), 88% were responders and no patients were
assigned to placebo.
There was no difference in cognitive function as assessed by
CANTAB in patients treated with UX007 compared to placebo.
Safety/Tolerability Results
Two of the 36 enrolled patients discontinued treatment during
the eight-week placebo-controlled period, and 12 patients have
discontinued during the extension period to date. Two patients
discontinued due to adverse events, four patients due to
tolerability reasons, and eight due to compliance or study burden
issues.
There were no deaths, and no treatment-related serious adverse
events. During the placebo-controlled period, 18 patients (72%) in
the UX007 arm had treatment-related adverse events (AEs) and five
patients (45%) in the placebo arm had treatment-related AEs. Most
AEs were mild-to-moderate GI events including vomiting, diarrhea,
and abdominal pain. Some gastrointestinal events were managed by
adjusting dosing or dosing with food.
Phase 2 study design
The randomized, double-blind, placebo controlled Phase 2 study
assessed the safety and efficacy of UX007 in patients with Glut1
DS. Thirty-six patients who met a pre-specified seizure count
criteria in either observable seizures, such as generalized
tonic-clonic or focal seizures, or absence seizures were randomized
in a 3:1 ratio to either UX007 or placebo. Dosing was
initiated over a 2-week titration period until the patient reached
the target dose of 35% of total daily calories from UX007. A daily
seizure diary was used to capture observable seizures and an
electroencephalography (EEG) was used at baseline and week 8 to
capture absence seizures. Following the double-blind period,
patients were given the option of rolling into an open-label
extension period during which they were treated with UX007.
Frequency reduction percentages provided are estimated based on the
pre-specified statistical modeling.
About Glut1 DS and UX007
Glut1 DS is a severely debilitating disease characterized by
seizures, developmental delay, and movement disorders. Glut1 DS is
caused by a genetic defect in the transport of glucose into the
brain. Because glucose is the primary source of energy for the
brain, this disorder results in a chronic state of energy
deficiency in the brain. Studies suggest a range of 3,000 to 7,000
Glut1 DS patients in the United States. There are currently no FDA
approved treatments specific to Glut1 DS, though patients with the
seizure phenotype are typically on the ketogenic diet.
UX007 is a highly purified, pharmaceutical-grade synthetic seven
carbon fatty acid triglyceride created via a multi-step chemical
process. It is an investigational medicine intended to provide
patients with medium-length, odd-chain fatty acids that can be
metabolized to increase intermediate substrates in the Krebs cycle,
a key energy-generating process. Unlike typical even-chain fatty
acids, UX007 can be converted to new glucose through the Krebs
cycle, potentially providing an important added therapeutic effect,
particularly when glucose levels are too low.
About Ultragenyx
Ultragenyx is a clinical-stage biopharmaceutical company
committed to bringing to market novel products for the treatment of
rare and ultra-rare diseases, with a focus on serious, debilitating
genetic diseases. Founded in 2010, the company has rapidly built a
diverse portfolio of product candidates with the potential to
address diseases for which the unmet medical need is high, the
biology for treatment is clear, and for which there are no approved
therapies.
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
regarding Ultragenyx's expectations regarding ongoing or additional
studies for its product candidates and timing regarding these
studies, 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, 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 uncertainties inherent in the clinical drug
development process, such as the regulatory approval process, the
timing of our regulatory filings and other matters that could
affect sufficiency of existing cash, cash equivalents and
short-term investments to fund operations and the availability or
commercial potential of our 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 the company in general, see Ultragenyx's Annual Report
on Form 10-K filed with the Securities and Exchange Commission on
February 17, 2017, and its subsequent periodic reports filed with
the Securities and Exchange Commission.
Contact Ultragenyx Pharmaceutical Inc.
Investors & Media
Ryan Martins
844-758-7273
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