Ultragenyx Announces the Presentation of Data From a Single Dose Phase 1 Study, Conducted by Kyowa Hakko Kirin Co. Ltd. (KHK), of KRN23 in X-linked Hypophosphatemia (XLH) in Adults

NOVATO, Calif., Oct. 6, 2013 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc., a biotechnology company, announced the release of data from a first-in-human, randomized, double-blind, placebo-controlled, single dose study of a human monoclonal anti-FGF23 antibody (KRN23) in X-linked hypophosphatemia in adults. X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease characterized by short stature and skeletal deformities. A Phase I study (US-02) was conducted by KHK with KRN23 to assess its safety and tolerability and to measure changes in biochemical markers in adult patients with XLH. Thirty-eight adults with XLH were randomized to receive single doses of KRN23 or placebo via intravenous (IV) (0.003 to 0.3 mg/kg) or subcutaneous (SC) (0.1 to 1.0 mg/kg) routes.

Data were presented by Thomas Carpenter, MD, Yale University at the American Society of Bone Mineralization Research (ASBMR) 2013 Annual Meeting on October 6, 2013. The study showed single doses of either IV or SC KRN23 increased serum phosphate level, renal absorption of phosphate and 1,25 dihydroxy Vitamin D compared to placebo (p < 0.01) for higher doses. Peak serum phosphate effects occurred later with SC (8-15 days) than with IV dosing (0.5-4 days). Duration of effect on phosphate was dose-related, greater with SC than IV, and persisted beyond 29 days with SC. No meaningful changes in serum calcium, serum parathyroid hormone, and urinary calcium excretion occurred. There were no SAEs, no discontinuations due to AEs and no changes in safety biochemistries, ECGs, or renal sonograms. AEs considered related to the study drug occurred in 6 patients (4 in IV dose groups [24%] and 2 in SC groups [17%]). Single dose administration of KRN23 was safe and well-tolerated; no patient developed anti-KRN23 antibodies.

"The study results suggest the potential to change the paradigm for treatment in XLH and we thank the investigators, patients and Kyowa Hakko Kirin for the successful conduct of the study," Emil D. Kakkis, M.D., Ph.D., Ultragenyx's Chief Executive Officer commented.

Ultragenyx and KHK plan to continue the development of KRN23 in adult XLH patients while planning to initiate a pediatric XLH program in 2014.

About X-linked Hypophosphatemia (XLH)

XLH is a disorder of phosphate metabolism caused by phosphate wasting in the urine leading to severe hypophosphatemia. XLH is the most common heritable form of rickets that is inherited as an X-linked dominant trait affecting both males and females, though some reports indicate that the disease may be more severe in males. XLH is a distinctive bone disease characterized by inadequate mineralization of bone that leads to a spectrum of abnormalities, including progressive bowing of the leg, osteomalacia, bone pain, waddling gait, short stature, gross motor impairment, muscle weakness, osteopenia, frequent/poorly healing microfractures, spinal stenosis and osteoarthritis.

Most patients are managed using oral phosphate replacement and vitamin D (calcitriol) therapy, which is poorly tolerated and only partially effective at restoring bone physiology and growth. Current treatment with oral phosphate requires close monitoring and can result in complications such as secondary hyperparathyroidism, hypercalciuria, hypercalcemia and nephrocalcinosis. XLH was originally called vitamin D-resistant rickets because doses of vitamin D effective for the treatment of vitamin D-deficient nutritional rickets did not have an impact on phosphate levels in these patients.

About KRN23 and FGF23

KRN23 is a recombinant fully human monoclonal IgG1 antibody discovered by KHK and being developed to treat X-linked hypophosphatemia (XLH). KRN23 is designed to bind to and thereby reduce the biologic activity of fibroblast growth factor 23 (FGF23). FGF23 is a hormone that promotes phosphate excretion by the kidney and suppresses vitamin D production. FGF23 also reduces the expression of the enzyme that is required to synthesize a hormone that normally increases renal tubular absorption of both phosphate and calcium. Therefore, FGF23 induces profound reductions in serum phosphate levels. Phosphate wasting in XLH is caused by excessive levels and activity of FGF23.

About Ultragenyx

Ultragenyx is a privately held, clinical-stage biotechnology company committed to bringing to market novel products for the treatment of rare and ultra-rare diseases, with an initial focus on serious, debilitating metabolic 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 areas of nephrology, oncology 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 contributing to the health and well-being of people around the world.

For more information, please visit the company's website at www.kyowa-kirin.com.

CONTACT: Ultragenyx Pharmaceutical Inc. 415-483-8800 For Media, Bee Nguyen bnguyen@ultragenyx.com For Investors, Shalini Sharp ssharp@ultragenyx.comSource:Ultragenyx Pharmaceutical Inc.