Study met primary endpoint of serum phosphorus
response and key secondary endpoint of stiffness improvement
Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), Kyowa Hakko Kirin
Co., Ltd. (Kyowa Hakko Kirin) and Kyowa Kirin International PLC, a
wholly owned subsidiary of Kyowa Hakko Kirin, today announced
positive 24-week data from the randomized, double-blind,
placebo-controlled Phase 3 study of burosumab (KRN23) in adults
with X-linked hypophosphatemia (XLH). Patients treated with
burosumab demonstrated a statistically significant improvement in
serum phosphorus levels, with 94% of patients achieving normal
levels compared to 8% on placebo (p<0.0001). Patients
treated with burosumab also achieved a statistically significant
improvement in stiffness and strong trends in improvements in
physical function and pain. Adverse events were consistent with
what has been previously observed in open label studies in adults
and children. Ultragenyx is conducting the study under a
collaboration and license agreement with Kyowa Hakko Kirin.
Burosumab is being developed by Ultragenyx, Kyowa Hakko Kirin and
Kyowa Kirin International.
“These data demonstrate a clinical improvement in patients
treated with burosumab and support the potential for treatment of
adults,” said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer
and President of Ultragenyx. “When combined with a favorable
safety profile and a strong serum phosphorus response, we believe
these clinical data should support regulatory submissions in adults
with XLH, and we look forward to discussing our filing plans with
the U.S. FDA.”
“This study provides valuable additional placebo controlled data
to that already obtained from the global clinical development
program for pediatric and adult patients with XLH.” said Mitsuo
Satoh, Executive Officer, Vice President, Head of Research and
Development Division of Kyowa Hakko Kirin. “I believe burosumab has
the potential to be an effective treatment option for patients with
XLH.”
“We are pleased that the data from this adult Phase 3 study
supports the safety and efficacy of burosumab and look forward to
progressing our discussions with the regulatory bodies in Europe
and the US,” said Dr. Tom Stratford, President and CEO of KKI.
Efficacy Results
The study enrolled 134 patients, randomized 1:1 to burosumab at
a dose of 1 mg/kg or placebo every four weeks for 24 weeks. The
study met the primary endpoint of increasing serum phosphorus
levels as 94% of patients treated with burosumab (n=68) achieved
serum phosphorus levels above the lower limit of normal and
maintained levels in the low normal range through 24 weeks,
compared to 8% in the placebo arm (n=66; p<0.0001).
There were three pre-specified key secondary endpoints,
including stiffness and physical function, both measured by the
Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC®), and pain measured by the Brief Pain Inventory Question 3
(BPI Q3; pain at its worst in the last 24 hours). At week 24
stiffness improved by a mean score of 7.87 points for patients
treated with burosumab compared to a 0.25 point worsening among
patients in the placebo group (mean difference of 8.12; p=0.0122).
Physical function improved by 3.11 points for patients treated with
burosumab compared to a 1.79 point worsening among patients in the
placebo group (mean difference of 4.90 points; p=0.0478). Pain
score improved by 0.79 for patients treated with burosumab compared
to a 0.32 improvement among patients in the placebo group (mean
score difference of 0.46 points; p=0.0919). Results were
directionally consistent towards improvement across all three key
secondary endpoints. After pre-planned multiplicity adjustment, the
improvement in stiffness among patients treated with burosumab
remained statistically significant at the less than the 0.0167
threshold, while physical function and pain scores demonstrated
strong trends.
Safety Results
There was no difference in the overall frequency of treatment
emergent adverse events, treatment related adverse events and
serious adverse events between the two treatment groups. The
most common (>10%) adverse events in patients treated with
either burosumab or placebo were back pain (burosumab 15%, placebo
9%), nasopharyngitis (burosumab 13%, placebo 9%), tooth abscess
(burosumab 13%, placebo 8%), injection site reactions (burosumab
12%, placebo 12%), headache (burosumab 12%, placebo 8%), restless
legs syndrome (burosumab 12%, placebo 8%), dizziness (burosumab
10%, placebo 6%), nausea (burosumab 10%, placebo 9%), arthralgia
(burosumab 9%, placebo 24%), pain in extremity (burosumab 7%,
placebo 15%) and oropharyngeal pain (burosumab 2%, placebo 11%).
There was no evidence of hypersensitivity reactions to injections.
There were two serious adverse events in each treatment group, none
of which were considered treatment-related. No differences between
groups were observed in serum intact parathyroid hormone levels or
ectopic mineralization as assessed by renal ultrasounds or
echocardiograms.
Of the 134 patients enrolled in the study, one patient in the
burosumab arm discontinued treatment during the 24-week
double-blind treatment period due to consent withdrawal. There have
been no deaths in the study.
About the Phase 3 Adult XLH Program
This Phase 3 study is a randomized, double-blind,
placebo-controlled clinical study designed to assess the efficacy
and safety of burosumab administered every four weeks in 134 adult
XLH patients in the US, EU, Canada, Japan, and Korea. The primary
endpoint of the study is the percentage of patients who achieved
average serum phosphorus levels in the normal range over 24 weeks.
The three key secondary endpoints are pain measured by BPI Q3,
stiffness and physical function, both measured by WOMAC®. After 24
weeks, all patients receive burosumab through the extension period
of the study.
Ultragenyx is conducting a second, fully-enrolled open-label
bone quality Phase 3 study in 14 adult XLH patients evaluating the
improvement in osteomalacia, the underlying bone pathology of XLH,
via bone biopsy. The bone quality study complements the phosphate
and patient symptom data from the larger Phase 3 XLH study by
evaluating the effect of burosumab more directly on the bone.
About Burosumab (KRN23)
Burosumab is an investigational recombinant fully human
monoclonal IgG1 antibody, discovered by Kyowa Hakko Kirin, against
the phosphaturic hormone fibroblast growth factor 23 (FGF23). FGF23
is a hormone that reduces serum levels of phosphorus and active
vitamin D by regulating phosphate excretion and active vitamin D
production by the kidney. Burosumab is being developed by
Ultragenyx and Kyowa Hakko Kirin to treat XLH and tumor-induced
osteomalacia (TIO), diseases characterized by excess levels of
FGF23. Phosphate wasting in XLH and TIO is caused by excessive
levels and activity of FGF23. Burosumab is designed to bind to and
thereby inhibit the biological activity of FGF23. By blocking
excess FGF23 in patients with XLH and TIO, burosumab is intended to
increase phosphate reabsorption from the kidney and increase the
production of vitamin D, which enhances intestinal absorption of
phosphate and calcium.
A clinical program studying burosumab in adults and pediatric
patients with XLH is ongoing. Burosumab is also being developed for
TIO, a disease characterized by typically benign tumors that
produce excess levels of FGF23, which can lead to severe
osteomalacia, fractures, bone and muscle pain, and muscle
weakness.
Details of Ultragenyx Conference Call
Ultragenyx will host a conference call today, Tuesday, April 18,
2017 at 4:30pm ET, during which Dr. Kakkis will discuss the topline
data. The live and replayed webcast of the call will be available
through the company's website at
http://ir.ultragenyx.com/events.cfm. To participate in the live
call by phone, dial 855-797-6910 (USA) or 262-912-6260
(international) and enter the passcode 10146009. The replay of the
call will be available for one year.
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.
About Kyowa Kirin
Kyowa Hakko Kirin Co., Ltd. is a research-based life sciences
company, with special strengths in biotechnologies. In the core
therapeutic areas of oncology, nephrology and immunology/allergy,
Kyowa Hakko Kirin leverages leading-edge biotechnologies centered
on antibody technologies, to continually discover innovative new
drugs and to develop and market those drugs world-wide. In this
way, the company is working to realize its vision of becoming a
Japan-based global specialty pharmaceutical company that
contributes to the health and wellbeing of people around the
world.
Kyowa Kirin International PLC (KKI) is a wholly owned subsidiary
of Kyowa Hakko Kirin and is a rapidly growing specialty
pharmaceutical company engaged in the development and
commercialisation of prescription medicines for the treatment of
unmet therapeutic needs in Europe and the United States. KKI is
headquartered in Scotland.
You can learn more about the business at:
www.kyowa-kirin.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, potential indications for its product candidates,
discussions with the FDA and sufficiency for, 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, 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
Contact Kyowa Kirin International PLC
Media
Callum Spreng
Spreng Thomson Ltd. (For Kyowa Kirin International PLC)
+44 (0)141 548 5191
Mobile: +44 (0)7803 970103
Email: callum@sprengthomson.com
Contact Kyowa Hakko Kirin Co. Ltd.
Media
Hiroki Nakamura
+81-3-5205-7205
Email: media@kyowa-kirin.co.jp
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