September 23, 2014 9:17am EDT
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Targeted Response Rate Achieved for Plasma Parathyroid Hormone
Reduction
Favorable Adverse Event Profile Consistent with First Phase 3 Trial
New Drug Application Submission to U.S. FDA Planned for End of 2014
MIAMI--(BUSINESS WIRE)--
OPKO Health, Inc. (NYSE: OPK), announced successful top-line results
from the second and final pivotal phase 3 trial of Rayaldee™. This trial
is the second 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 established with the United States
(U.S.) Food and Drug Administration (FDA) in August 2012.
“Top-line data from this second study confirmed 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, M.D., Vice President of Clinical
Research and Development for OPKO’s Renal Division. “As with the first
trial, 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 216 adult patients recruited from 38 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 vs. 8% of patients treated with placebo.
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 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.
Patients who completed the two pivotal trials are being treated, at
their election, for an additional 6 months with Rayaldee during an
open-label extension study. Enrollment in this extension study is
complete at 298 patients, of which 180 (69%) patients have completed
participation.
“The data from the two pivotal phase 3 studies, when combined with the
available data from the ongoing open-label extension study, provide a
clear picture of Rayaldee’s efficacy during longer-term administration,”
commented Dr. Charles W. Bishop, Ph.D., CEO of OPKO’s Renal Division.
“The gradual but progressive PTH lowering observed during 6 months of
treatment in the pivotal trials is continuing during 6 additional months
of treatment in the extension study, allowing PTH levels to return to
the normal range in a significant proportion of patients.”
“Gradual reduction of elevated PTH towards the normal range is likely to
become the new treatment goal for predialysis patients whose secondary
hyperparathyroidism has not become firmly established,” stated Stuart M.
Sprague, DO, Chief, Division of Nephrology and Hypertension, NorthShore
University Health System - University of Chicago, Pritzker School of
Medicine. “Currently, these patients are treated with high doses of
nutritional vitamin D, but fewer than 50% show an adequate response.
Inadequate correction of vitamin D insufficiency with nutritional
vitamin D allows secondary hyperparathyroidism to become established and
less responsive to treatment. The phase 3 data with Rayaldee show that
this product is highly effective in correcting vitamin D insufficiency,
allowing more reliable treatment of these patients.”
“OPKO is committed to improving the care of patients with chronic kidney
disease by developing safer and more effective therapies for secondary
hyperparathyroidism than those available today,” commented Phillip
Frost, M.D., Chairman and CEO of OPKO Health. “Rayaldee provides an
excellent solution to the problem of secondary hyperparathyroidism
associated with vitamin D insufficiency for the 20 million pre-dialysis
CKD patients in the U.S. and many more elsewhere.”
A New Drug Application submission to the FDA is planned for the end of
2014.
About Rayaldee TM
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 8 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 20 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 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, that Rayaldee will effectively
control secondary hyperparathyroidism in patients with stage 3 or 4
chronic kidney disease by correcting vitamin D insufficiency, whether
Rayaldee is appropriate for patients with minimal functioning kidney
mass and its efficacy during longer term administration, whether
Rayaldee will be highly effective in correcting vitamin D insufficiency,
allowing more reliable treatment of patients, whether it is the solution
to secondary hyperparathyroidism associated with vitamin D insufficiency
for the 20 million pre-dialysis CKD patients in the U.S. and elsewhere,
market potential for Rayaldee, 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, the expected timing of the NDA submission, 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 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.
Charles W. Bishop, 305-575-4100
Source: OPKO Health, Inc.
Released September 23, 2014
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