August 11, 2014 4:15pm EDT
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Top-line Data from Second Identical Pivotal Phase 3 Trial Expected in
September 2014
New Drug Application (NDA) Submission to the U.S. FDA on Track for End
of 2014
MIAMI--(BUSINESS WIRE)--
OPKO Health, Inc. (NYSE: OPK), announced successful top-line results
from the first pivotal phase 3 trial of Rayaldee™. This trial is one of
two identical randomized, double-blind, placebo-controlled, multi-site
studies intended to establish the safety and efficacy of Rayaldee as a
new treatment for secondary hyperparathyroidism (SHPT) in patients with
stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency.
Both trials are the subject of a Special Protocol Assessment (SPA)
established with the United States (U.S.) Food and Drug Administration
(FDA) in August 2012.
“Top-line data from this study demonstrate that Rayaldee effectively
controls secondary hyperparathyroidism in patients with stage 3 or 4
chronic kidney disease by correcting vitamin D insufficiency,” stated
Joel Z. Melnick, MD, Vice President of Clinical Research and Development
for OPKO’s Renal Division. “Rayaldee was equally effective in both
disease stages, indicating that this new therapy is appropriate even for
patients with minimal functioning kidney mass.”
This trial involved 213 adult patients recruited from 39 sites
throughout the U.S. Patients were stratified by CKD stage and randomized
in a 2:1 fashion to receive six months of treatment with either Rayaldee
or placebo. On enrollment, all patients exhibited vitamin D
insufficiency which was corrected in 96% of patients treated with
Rayaldee.
The completed trial successfully met all primary efficacy and safety
endpoints. The primary efficacy endpoint was a responder analysis in
which “responder” was defined as any treated subject who demonstrated an
average 30% decrease in plasma parathyroid hormone (PTH) from
pre-treatment baseline during the last six weeks of the treatment
period. A significantly higher response rate (p<0.001) was observed with
Rayaldee which steadily increased with treatment duration. The response
rate with Rayaldee was similar in CKD stages 3 and 4. Safety and
tolerability data were comparable in both treatment groups.
“Rayaldee is designed to fill a void in the treatment armamentarium of
nephrologists and endocrinologists who care for pre-dialysis chronic
kidney disease patients,” commented Dr. Charles W. Bishop, CEO of OPKO’s
Renal Division. “Controlled trials have shown that over-the-counter and
prescription vitamin D supplements are ineffective in treating SHPT in
these patients and are, at best, unreliable in correcting vitamin D
insufficiency. On the other hand, vitamin D hormone drugs can
effectively treat SHPT but, due to high potency, often oversuppress PTH,
increasing the risk of adynamic bone disease and vascular calcification.
These hormone drugs are entirely ineffective in treating vitamin D
insufficiency, the underlying cause of SHPT in most pre-dialysis
patients. Rayaldee addresses a long-standing unmet need to safely
control SHPT by reliably correcting vitamin D insufficiency.”
“Physicians will embrace a product that does what we want, namely, treat
vitamin D insufficiency and gradually correct elevated PTH, without
safety concerns,” stated David A. Bushinsky, MD, Chief, Nephrology
Division, University of Rochester Medical Center. “Data from this first
pivotal trial indicate that Rayaldee may be such a product, and I look
forward to confirmation from the second identical trial.”
Top-line data from the second, identical pivotal phase 3 trial are
expected to be available in September 2014.
Patients completing the two pivotal trials are being treated, at their
election, for an additional 6 months with Rayaldee during an ongoing
open-label extension study. Enrollment in this extension study surpassed
the targeted level of 270 patients by May 2014 and 141 patients have
completed participation.
“Rayaldee is the lead candidate in a growing portfolio of products that
OPKO is developing in its Renal Division for global commercialization,”
explained Dr. Phillip Frost, Chairman and CEO of OPKO Health. “Rayaldee
provides an excellent solution to the problem of secondary
hyperparathyroidism associated with vitamin D insufficiency for more
than 4 million CKD patients in the U.S. and many more elsewhere.”
A New Drug Application (NDA) submission to the U.S. FDA is on track for
the end of 2014.
About Rayaldee™
Rayaldee is a first-in-class oral vitamin D prohormone treatment being
developed for SHPT in patients with stage 3 or 4 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
patients have vitamin D insufficiency, which can lead to SHPT and
resultant debilitating bone diseases. Vitamin D insufficiency has been
associated with increased mortality in CKD.
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 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 in CKD patients.
About Special Protocol Assessment
The Special Protocol Assessment (SPA) provided a mechanism for the FDA
and OPKO to reach agreement on the design, size, execution and analysis
of the two pivotal phase 3 trials with Rayaldee. The FDA agreed that the
design and planned analysis of these studies adequately addressed the
objectives necessary to support an NDA submission.
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 U.S. and many more elsewhere, with SHPT and vitamin D insufficiency,
that Rayaldee™ will treat vitamin D insufficiency and gradually correct
elevated PTH, without safety concerns, 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 phase 3 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 D 2 , 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.
OPKO Health, Inc.
FTI Consulting
Barbara
Ryan, 212-850-5679
Managing Director
or
Media
Kimberly Ha, 212-850-5612
Senior Director
Source: OPKO Health, Inc.
Released August 11, 2014
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