Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical
company focused on the development of novel products for rare and
ultra-rare diseases, today announced positive interim data from the
Phase 2 study of KRN23 for the treatment of tumor-induced
osteomalacia (TIO). Interim data at 24 weeks from the first eight
patients, including one patient with epidermal nevus syndrome
(ENS), demonstrated that KRN23 improved serum phosphorus levels and
bone metabolism measures. Ultragenyx is conducting the Phase 2
study under a collaboration and license agreement with Kyowa Hakko
Kirin to develop and commercialize KRN23. These data were presented
today at the American Society for Bone and Mineral Research (ASBMR)
2016 Annual Meeting.
“Patients with TIO have substantial hypophosphatemia,
osteomalacia and fractures,” said Emil D. Kakkis, M.D., Ph.D.,
Chief Executive Officer and President of Ultragenyx. “These data
support that KRN23 could potentially reverse some of these symptoms
and improve bone health in patients.”
Mean serum phosphorus, renal phosphate reabsorption (TmP/GFR)
and serum 1,25 dihydroxy vitamin D levels increased over 24 weeks
of treatment. Before KRN23 treatment and after washout with any
oral phosphate treatment, the mean serum phosphorus level was 1.7
mg/dL, well below the lower limit of normal of 2.5 mg/dL. The mean
serum phosphorus level entered the normal range within one week of
treatment, and was maintained in the low normal range from week 10
to week 24 of treatment. Overall, the improvement in serum
phosphorus and other bone mineral metabolism measures observed in
this study to date is generally consistent with what has been
observed in studies of KRN23 in pediatric and adult patients with
X-linked hypophosphatemia (XLH).
Of the seven patients who responded, six patients showed an
improvement in bone mineral density at 24 weeks of treatment. Bone
turnover markers, including Procollagen type 1 N-terminal
propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1),
showed a statistically significant increase. One patient
completed 48 weeks of treatment, at which time bone biopsies
indicated an improvement from severe osteomalacia at baseline to
mild osteomalacia at 48 weeks. The same patient showed
resolution of four fractures at 24 weeks of treatment, determined
by bone scan as previously disclosed. Bone mineral density for this
patient improved 2% and 3% in the lumber spine and total hip,
respectively. Bone biopsy and bone scan data for additional
patients will be available at a later date.
Adverse events occurred in all patients. Treatment-related
adverse events were observed in three patients (38%), and included
Vitamin D deficiency and rash as previously disclosed, and
dysgeusia, all mild in grade. There was one serious adverse event
of neoplasm progression, which occurred in one patient with
pre-existing metastatic spindle sarcoma who did not respond and has
discontinued treatment. No injection site reactions were observed.
Two patients had restless leg syndrome, one of whom had symptoms
suggestive of worsening pre-existing restless leg syndrome. No
clinically meaningful changes were observed in mean serum calcium,
urinary calcium and in serum intact parathyroid hormone.
Conference Call Details
Ultragenyx will host a conference call on Monday, September 19
at 11am ET during which Dr. Kakkis will discuss results of the
KRN23 studies being presented at the ASBMR Annual Meeting. 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 83882106. The
replay of the call will be available for one year.
Phase 2 Study Design
The open-label, dose-finding Phase 2 clinical study is
evaluating the safety and efficacy of KRN23 in 17 adult patients.
The primary objectives of the study are to establish the dose, and
assess the safety profile and efficacy of treatment with KRN23 in
adults with TIO and ENS whose tumors or lesions cannot be resected.
Patients receive subcutaneous injections of KRN23 once every four
weeks for 48 weeks. All patients begin treatment with KRN23 at a
starting dose of 0.3 mg/kg. Doses are then titrated in an effort to
achieve a target fasting serum phosphorus range of 2.5 to 4.0
mg/dL. After completing the initial 48-week treatment period of the
study, patients may continue into a planned treatment extension
period in which they receive KRN23 treatment for up to an
additional 96 weeks. The co-primary endpoints include: the
proportion of patients achieving mean peak serum phosphorus levels
above the lower limit of normal (LLN; 2.5 mg/dL), as averaged
between baseline and week 24; and the percent change from baseline
in excess osteoid after 48 weeks of treatment. Preliminary clinical
effects of KRN23 treatment will be evaluated by radiographic
assessments, muscle strength, walking ability, and by
patient-reported measures of pain, disability, and quality of life.
Markers of bone health and changes in serum phosphorus and other
biochemical measures are also followed.
KHK is conducting a separate Phase 2 study evaluating the safety
and efficacy of KRN23 in 12 adult patients in Japan.
About TIO
TIO, and a skin lesion variant, epidermal nevus syndrome
(ENS)-associated osteomalacia, are caused by typically benign
tumors or lesions that produce excess levels of FGF23, causing
phosphate wasting in the urine that leads to severe
hypophosphatemia, osteomalacia, muscle weakness, fatigue, bone
pain, and fractures. The symptoms rapidly resolve if the causal
tumors or lesion can be resected; however, there are cases in which
resection is not feasible or recurrence of the tumor occurs after
resection. In patients for whom the tumor or lesion is inoperable,
the current treatment consists of oral phosphate and/or vitamin D
replacement. Efficacy of this treatment is often limited, as it
does not treat the underlying disease and its benefits must be
balanced with monitoring for potential risks such as
nephrocalcinosis, hypercalciuria, and hyperparathyroidism. There
are an estimated 500-1,000 patients with TIO in the United States,
and approximately half of all cases are inoperable.
About KRN23
KRN23 is an investigational recombinant fully human monoclonal
IgG1 antibody, discovered by Kyowa Hakko Kirin, against the
phosphaturic hormone fibroblast growth factor 23 (FGF23). It is
being developed by Ultragenyx and Kyowa Hakko Kirin to treat XLH
and TIO, diseases characterized by excess activity of FGF23. FGF23
is a hormone that reduces serum levels of phosphorus and vitamin D
by regulating phosphate excretion and vitamin D production by the
kidney. Phosphate wasting in XLH and TIO is caused by excessive
levels and activity of FGF23. KRN23 is designed to bind to and
thereby inhibit the excessive biological activity of FGF23. By
blocking excess FGF23 in patients with XLH and TIO, KRN23 is
intended to increase phosphate reabsorption from the kidney and
increase the production of vitamin D, which enhances intestinal
absorption of phosphate and calcium.
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 Hakko Kirin
Kyowa Hakko Kirin is a leading biopharmaceutical company in
Japan focusing on its core business area of oncology, nephrology,
and immunology/allergy. Kyowa Hakko Kirin leverages
antibody-related leading-edge technologies to discover and develop
innovative new drugs aiming to become a global specialty
pharmaceutical company which contributes to the health and
well-being of people around the world.
For more information, please visit 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 the timing of release
of additional data for its product candidates, plans to initiate
additional studies for its product candidates and timing regarding
these studies, plans regarding ongoing studies for existing
programs and its intent to file for conditional approval, 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,
including the regulatory approval process, the timing of our
regulatory filings, and other matters that could affect the success
of our drug development programs, including KRN23. 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 Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission on August 9, 2016, 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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