August 07, 2014 3:35pm EDT
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MIAMI--(BUSINESS WIRE)--
OPKO Health, Inc. (NYSE: OPK), announced the submission of an
Investigational New Drug (IND) Application to the United States (U.S.)
Food and Drug Administration (FDA) under which Rayaldee ™ will
begin clinical evaluation as an adjunctive therapy for the prevention of
skeletal-related events (SREs) in patients with bone metastases
undergoing anti-resorptive therapy.
The initial investigation described in this IND is a phase 1 dose
titration study designed to evaluate the safety and tolerability of Rayaldee
in patients with breast or prostate cancer that has metastasized to bone
who are receiving treatment with zoledronic acid (a bisphosphonate) or
denosumab (a RANKL inhibitor). Approximately 24 subjects (12 with each
cancer type) will receive Rayaldee at a starting daily dose of 30
µg (1 capsule) for 4 weeks. The dose will escalate in 30 µg increments
at 4-week intervals until predetermined biochemical endpoints are
reached, at which time the subjects will enter a 12-week maintenance
phase. Safety parameters and various markers of bone metabolism, immune
function and tumor burden will be monitored at regular intervals.
This study is expected to commence later this year and to take
approximately 18 months to complete. Following evaluation of this
initial study, OPKO plans to conduct subsequent studies investigating
the effects of Rayaldee on SREs and other parameters deemed to
indicate potential clinical benefits in the targeted population.
About Rayaldee ™
Rayaldee is a first-in-class oral vitamin D prohormone treatment
in late-stage clinical development for secondary hyperparathyroidism
(SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and
vitamin D insufficiency. It has a proprietary modified-release
formulation designed to gradually and reliably raise serum total
25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at
least 30 ng/mL) while avoiding upregulation of CYP24, a cytochrome P-450
enzyme that reduces the PTH-lowering potency of current vitamin D
supplements. Activation of calcifediol, the active ingredient in Rayaldee ,
by the kidney is tightly regulated, preventing excessive elevation of
serum calcium and related side effects which limit the value of current
vitamin D hormone therapies by promoting vascular and renal
calcification. Rayaldee is expected to address the approximately
4 million patients in the U.S. and many more elsewhere, with stage 3 or
4 CKD, SHPT and vitamin D insufficiency.
About Chronic Kidney Disease
CKD is a condition characterized by a progressive decline in kidney
function. The kidney is normally responsible for excreting waste and
excess water from the body, and for regulating various hormones. CKD is
classified in five different stages — mild (stage 1) to severe (stage 5)
disease — as measured by the kidney's glomerular filtration rate.
According to the National Kidney Foundation, CKD afflicts over 26
million people in the U.S., including more than eight million patients
with moderate (stages 3 or 4) and severe (stage 5) forms of CKD. In
stage 5 CKD, kidney function is minimal to absent and patients require
regular dialysis or a kidney transplant for survival.
About Vitamin D Insufficiency
Vitamin D insufficiency is a condition in which the body has low vitamin
D stores, characterized by inadequate blood levels of vitamin D
prohormone, known as 25-hydroxyvitamin D. An estimated 70-90% of CKD and
cancer patients have vitamin D insufficiency, which can lead to SHPT,
hypocalcemia (low serum calcium) and resultant debilitating bone
diseases. Vitamin D insufficiency has been associated with increased
mortality in CKD and various cancers.
About Secondary Hyperparathyroidism (SHPT)
SHPT is a condition commonly associated with CKD in which the
parathyroid glands secrete excessive amounts of PTH. SHPT arises as a
result of vitamin D insufficiency, use of anti-resorptive therapies, or
impaired kidney function that prevents sufficient production of vitamin
D hormone to properly regulate calcium and phosphorus metabolism, and
PTH secretion. Prolonged elevation of blood PTH causes excessive calcium
and phosphorus to be released from bone, leading to elevated serum
calcium and phosphorus, softening of the bones (osteomalacia) and
calcification of vascular and renal tissues. SHPT affects 40-60% of
patients with moderate CKD and approximately 90% of patients with severe
CKD. Vitamin D therapy for SHPT is associated with reduced mortality.
About Anti-Resorptive Therapy for Metastatic Bone Cancer
Anti-resorptive therapy effectively reduces bone loss caused by cancer
progression, thereby preventing or delaying SREs. This therapy causes
SHPT and increases the risk of serious hypocalcemia which can be fatal.
Risk of SHPT and hypocalcemia is elevated in patients who are receiving
anti-resorptive therapy due to the high prevalence of vitamin D
insufficiency, which reduces intestinal absorption of dietary calcium.
About Skeletal-Related Events (SREs)
Bone metastases are a common in advanced breast and prostate cancer, and
represent a major cause of morbidity and mortality. In the absence of
anti-resorptive therapy, they produce hypercalcemia, pathological
fractures and spinal cord compression, collectively known as
skeletal-related events (SREs). Current approaches to management of SREs
include suppressing osteolytic activity with zoledronic acid (a
bisphosphonate) or denosumab (an antibody targeting RANK ligand). These
anti-resorptive agents are highly effective but increase the risk of
fatal hypocalcemia.
Anti-resorptive agents reduce the efficiency of PTH-stimulated release
of calcium from bone, promoting SHPT and forcing reliance on intestinal
calcium absorption for calcium homeostasis. Since cancer patients
frequently have poor dietary intake (due to cachexia) and vitamin D
insufficiency, intestinal calcium absorption can be inadequate. In a
recent study, 39% of patients treated with zoledronic acid developed
hypocalcemia, and numerous other studies have reported reduced serum
calcium with denosumab treatment. Labeling for both agents requires
correction of hypocalcemia before dosing and ongoing supplementation
with calcium and vitamin D during therapy.
About OPKO
OPKO is a multinational biopharmaceutical and diagnostics company that
seeks to establish industry leading positions in large, rapidly growing
markets by leveraging its discovery, development and commercialization
expertise and novel and proprietary technologies.
This press release contains "forward-looking statements," as that
term is defined under the Private Securities Litigation Reform Act of
1995 (PSLRA), regarding product development efforts and other
non-historical facts about our expectations, beliefs or intentions
regarding our business, technologies and products, financial condition,
strategies or prospects, including statements regarding our ability to
successfully launch and commercialize proprietary renal disease
products, expectations about Rayaldee™, its market potential, that it
will address the approximately 4 million CKD stage 3 and 4 patients in
the US and many more elsewhere, with SHPT and vitamin D insufficiency,
whether it will be an effective adjunctive therapy for the prevention of
SREs in patients with bone metastases, expectations about the timing to
commence and complete clinical studies for Rayaldee, and that we will be
able to successfully develop, obtain approval for and launch sales of
Rayaldee™. Many factors could cause our actual activities or results to
differ materially from the activities and results anticipated in
forward-looking statements. These factors include those described in our
filings with the Securities and Exchange Commission, as well as risks
inherent in funding, developing and obtaining regulatory approvals of
new, commercially-viable and competitive products and treatments,
including the risks that the clinical trials for Rayaldee™ may not be
successful or achieve the expected results or effectiveness, and may not
generate data that would support the approval or marketing of this
product for the indications being studied, that others may develop
products which are superior to Rayaldee™, and that Rayaldee™ may not
have advantages or prove to be superior over presently marketed
products, including the currently used high monthly doses of
prescription vitamin D2, activated vitamin D hormone and
over-the-counter vitamin D supplements . In addition, forward-looking
statements may also be adversely affected by general market factors,
competitive product development, product availability, federal and state
regulations and legislation, the regulatory process for new products and
indications, manufacturing issues that may arise, patent positions and
litigation, among other factors. The forward-looking statements
contained in this press release speak only as of the date the statements
were made and we do not undertake any obligation to update
forward-looking statements. We intend that all forward-looking
statements be subject to the safe-harbor provisions of the PSLRA.
FTI Consulting
Barbara
Ryan, 212-850-5679
Managing Director
or
Media
Kimberly Ha, 212-850-5612
Senior
Director
Source: OPKO Health, Inc.
Released August 7, 2014
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