NPS Announces Positive Phase III Study Results for PREOS(R) in Women With Osteoporosis
TOP Study Meets Primary Endpoint of Vertebral Fracture Reduction
Company to File NDA Later This Year
SALT LAKE CITY, March 30 /PRNewswire-FirstCall/ -- NPS Pharmaceuticals,
Inc. (Nasdaq: NPSP) announced today that its pivotal Phase III study of PREOS
successfully met the primary endpoint of reducing the incidence of new or
worsened vertebral fractures in postmenopausal women with mild to moderate
osteoporosis, and that the company is proceeding with plans to submit an
application later this year to the U.S. Food and Drug Administration for
approval to market the drug.
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PREOS is recombinant human parathyroid hormone (PTH), which has been shown
in previous human studies and animal tests to stimulate bone turn-over
processes, resulting in a net increase in healthy, fracture-resistant bone.
TOP Study Design
The PREOS Phase III study, known as TOP (Treatment of Osteoporosis with
PTH), was a multi-center, randomized, double-blind, placebo-controlled
clinical trial designed to evaluate the potential of PTH to reduce the risk of
vertebral fracture in women who represent a broad population of osteoporosis
patients. Investigators at 152 clinical centers worldwide enrolled
approximately 2,600 postmenopausal women with osteoporosis who were not
required to have a disease-related vertebral fracture prior to entering the
trial, but were required to have osteoporosis as defined by low bone mineral
density (BMD). The average pre-trial vertebral T-score of study participants
was -3.0, meaning an average BMD measurement of three standard deviations
below the mean BMD of healthy young women. Most study participants (81%) did
not have a vertebral fracture prior to entering the study.
Patients in the study were randomized to receive either a daily
subcutaneous injection of 100 micrograms of PREOS or a placebo, plus daily
supplements of calcium (700 milligrams) and vitamin D (400 IU) over a period
of 18 months. Approximately 1,700 TOP study participants have enrolled to
receive PREOS as part of an ongoing open label extension study known as OLES.
The primary endpoint in the TOP study was a reduction in the incidence of
new or worsened vertebral fractures in patients receiving PREOS, compared to
patients who received a placebo. Secondary endpoints in the study included
evaluation of fractures at bone sites other than the spine, changes in BMD,
and other measures of new bone growth and quality.
TOP Study Findings
An analysis of all patients receiving at least one dose of PREOS or
placebo showed a statistically significant (p-value = 0.001) reduction in the
relative risk of vertebral fractures for patients in the treatment group,
compared to the placebo group. The rate of vertebral fractures in the placebo
group was 3.4 percent (42 new vertebral fractures), consistent with mild to
moderate disease severity, while the rate of vertebral fractures in the
PREOS-treated group was 1.4 percent (17 new vertebral fractures and one
worsened vertebral fracture), demonstrating a 59 percent relative reduction in
vertebral fracture risk. A 68 percent relative reduction in vertebral
fracture risk (p-value = 0.006) was achieved in patients treated with PREOS
who entered the trial without a previous fracture. At month twelve, patients
who had taken daily PREOS, calcium, and vitamin D had a 60 percent reduction
in the relative risk of new vertebral fractures, though this finding was not
statistically significant (p-value = 0.122). Overall, patients treated with
PREOS in the TOP study had fewer total fractures at non-vertebral sites
compared to placebo patients, but these differences were not statistically
significant. Subgroup analysis with regard to these measurements and other
clinical endpoints is ongoing.
The average change in vertebral BMD in all patients receiving at least one
dose of PREOS was 7 percent relative to placebo patients (p-value < 0.001).
Other measures of bone growth and quality were positive and consistent with
previous human clinical trial results with PREOS.
The percentage of patients experiencing adverse events and serious adverse
events was comparable in the PREOS-treated and placebo groups, and consistent
with previous studies. The two most frequent adverse events in the PREOS
group were elevated levels of serum and urine calcium, which were generally
consistent with observations from the PREOS Phase II study. In the majority
of patients with elevated levels of serum or urine calcium these values
returned to normal upon retest or upon entering an algorithm that allowed for
a reduction of the daily calcium supplement or study drug, as is customary in
other studies of PTH-related compounds. Other frequent side effects included
headaches, nausea, dizziness and vomiting. Approximately 9 percent of
patients receiving PREOS dropped out of the study as a result of elevated
levels of serum or urine calcium, or due to headaches, nausea, dizziness, or
vomiting, while about 2 percent of placebo patients dropped out due to one or
more of these side effects. Approximately 16 percent of PREOS-treated patients
dropped out of the TOP study due to any side effect, compared to approximately
10 percent of patients in the placebo group.
These findings represent an initial analysis of results from the TOP
study. Investigators from the TOP study will present more complete trial
results at appropriate scientific meetings and in peer-reviewed publications.
Clinical Significance of TOP Study Findings
Robert Lindsay, M.D., Chief of Medicine at Helen Hayes Hospital, Professor
of Medicine at Columbia University, and head of the independent data and
safety monitoring board for the TOP study, stated: "The TOP study findings
are encouraging and indicate that this drug can build healthy new bone and
prevent the occurrence of first-time vertebral fractures in women with mild to
moderate osteoporosis. The findings are particularly important because once
people have suffered the first fracture they are at significantly higher risk
for additional fractures. Avoiding the first fracture is therefore an
important clinical goal, and the TOP study indicates the need to build bone in
women with low BMD in order to accomplish this."
Alan Rauch, M.D., Chief Medical Officer at NPS, said: "We are very
pleased with the results of the TOP study. We believe that the reduction in
fracture risk seen in this study suggests that PREOS promises to be an
effective alternative for physicians when choosing appropriate therapies for
their patients who have mild osteoporosis, as well as in patients with more
serious disease. We will continue to analyze the large amount of data
collected in the TOP study as we prepare our NDA submission so that we will
have a thorough understanding of how PREOS may best be used."
Ongoing Clinical Trials with PREOS
NPS is continuing to evaluate the use of PREOS in patients participating
in the open label extension of the TOP study, and data from the POWER (PTH in
Osteoporotic Women on Estrogen Replacement) study of PTH combined with
estrogen replacement therapy and the NIH-sponsored two-year PaTH (PTH and
alendronate) study.
Conference Call Information
NPS will host a conference call today at 8:30 a.m., EST, to discuss these
findings. To participate in the call, dial (800) 374-0232 and use
confirmation code 6400995. International callers may dial (706) 634-6338,
using the same confirmation code. In addition, live audio of the conference
call will be simultaneously broadcast over the Internet and may be accessed
under the Investor Relations page, Calendar of Events section of the company's
web site ( npsp.com ). Please click on the webcast link and follow the
prompts for registration and access.
If you are unable to participate in the live call, a replay will be
available at (800) 642-1687 (with confirmation code 6400995) until midnight,
EST, April 6, 2004. International callers may access the replay by dialing
(706) 645-9291, using the same confirmation code. The webcast will also be
available on the NPS website for the same period of time.
About NPS Pharmaceuticals
NPS discovers, develops and intends to commercialize small molecules and
recombinant proteins as drugs, primarily for the treatment of metabolic, bone
and mineral, and central nervous system disorders. The company has drug
candidates in various stages of clinical development backed by a strong
discovery research effort. Additional information is available on the
company's website, npsp.com .
Safe Harbor Statement
Note: Statements made in this press release, which are not historical in
nature, constitute forward-looking statements for purposes of the safe harbor
provided by the Private Securities Litigation Reform Act of 1995. Such
statements include those regarding the likelihood that PREOS will be an
appropriate therapy for patients who have osteoporosis of mild to moderate
severity; our intent to file an NDA for PREOS later this year; and our intent
to commercialize small molecules and recombinant proteins as drugs. These
statements are based on management's current expectations and beliefs and are
subject to a number of factors and uncertainties that could cause actual
results to differ materially from those described in the forward-looking
statements. Such risks and uncertainties include: we may not be able to
collect, assemble and analyze data from the PREOS trials in a timely manner;
the data from the TOP study may not justify filing an NDA for PREOS; we have
never filed an NDA and may not be able to do so in a timely manner; we do not
have and may never develop any products that generate revenues; our product
candidates may not prove to be safe or efficacious; the FDA may delay approval
or may not approve any of our product candidates; current collaborators or
partners may not devote adequate resources to the development and
commercialization of our licensed drug candidates which would prevent or delay
introduction of drug candidates to the market; we may be unable to generate
adequate sales and marketing capabilities to effectively market and sell our
products; failure to secure adequate manufacturing and storage sources for our
products could result in disruption or cessation of our clinical trials and
eventual commercialization of such products; and we may not have or be able to
secure sufficient capital to fund development and commercialization of our
product candidates. All information in this press release is as of
March 30, 2004, and we undertake no duty to update this information. A more
complete description of these risks can be found in our filings with the
Securities and Exchange Commission, including our Annual Report on Form 10K/A
for the year ended December 31, 2003. |
