- Phase I-B Obesity Clinical Trial Demonstrates PYY-Related Appetite
Suppression, Calorie Reduction and an Acceptable Safety Profile -
- Phase II Maximum Tolerated Dose Erectile Dysfunction Clinical Trial
Demonstrates Apomorphine is Safe and Well Tolerated at Doses Significantly
Above Efficacious Doses -
BOTHELL, Wash., March 10 /PRNewswire-FirstCall/ -- Nastech Pharmaceutical
Company Inc. (Nasdaq: NSTK), a leader in drug delivery technology, today
reported positive results from a Phase I-B study with PYY 3-36 (PYY) nasal
spray for obesity and positive results from a Phase II Maximum Tolerated Dose
(MTD) study with apomorphine nasal spray for sexual dysfunction.
PYY 3-36 PHASE I-B CLINICAL STUDY
In January 2004, Nastech initiated a Phase I-B dose-range finding study in
healthy overweight men and women with a Body Mass Index of 27-40 kg/m2. The
study was a randomized five-way crossover, double-blind, placebo-controlled
trial with assessment of appetite and food intake for the 24-hour period (from
lunch one day to breakfast the next day) following a single administration of
a PYY nasal spray or a placebo nasal spray before the lunch meal.
Pharmacokinetics, vital signs, nasal tolerance and safety were also evaluated.
Eleven subjects completed the study; one dropped out due to problems of
venous access for the blood draws. Results in 9 of 11 subjects indicate that
a single dose of PYY nasal spray reduced average calorie intake for each meal,
with the greatest reduction at the lunch meal, and overall for the 24-hour
period. PYY also reduced appetite, as determined by Visual Analog Scale
assessment, and was well tolerated; side effects were generally mild and all
resolved without treatment. Two subjects did not respond. Nastech is
developing intellectual property around the understanding of this difference.
The mean reduction in lunch time calories following all doses of PYY was
8.2% in the 9 of 11 responders. The mean reduction in lunch calories
following the single most effective dose of PYY was 23% in responders. Five
of eleven subjects had a reduction in calorie consumption of 24% or greater
after one of the PYY doses and two subjects had a reduction of over 55% after
one of the PYY doses compared to the placebo treatment.
As measured by Visual Analog Scores, all nasal PYY administrations
produced a reduction in hunger scores compared with placebo. For example, at
60 minutes after administration, mean hunger scores were lower than baseline
by 2% for placebo and by 5% to 19% for different PYY dosage groups. Despite
the single dose and relatively short half-life (about 1 hour in our I-A
study), cumulative 24-hour hunger scores were also reduced for subjects
receiving PYY compared to placebo. Similar PYY-dependent changes were seen
for VAS questions related to fullness and the amount they thought they could
eat. That is, the PYY treated subjects, although blinded to treatment, stated
they were less hungry, had a greater feeling of fullness and thought they
could eat less food after receiving PYY compared to placebo.
The mean reduction in 24-hour total calories for all doses was 4% while
the mean reduction for the most effective single dose was 15%. Four subjects
had reduced 24-hour calorie intake over 15% with two of those subjects over
30% comparing PYY administration to placebo. This calorie reduction was
observed in a setting of boundless, attractive food choices, a single dose of
PYY, and the absence of diet counseling or instructions about eating behavior.
To put this in perspective, the average American adult consumes 2,750 calories
per day, and a 4% to 15% daily calorie reduction and without other changes
would produce an approximate 11 to 43 pound annual weight loss. Increasing
dose concentration, frequency or more importantly, invoking some diet and/or
exercise intervention, could improve these results.
PYY was well tolerated in this study. All adverse events but one were
rated as mild; one was rated as moderate. All resolved without treatment.
Following placebo administration, we observed one episode each of drowsiness,
headache and nasal congestion possibly related to administration, in this
case, of the placebo. Nasal administration of PYY produced one episode each
of bloating and dry throat at the lowest PYY dose; one report of lethargy,
headache, blurred vision, and nausea and two episodes of throat dryness at the
middle PYY dose; and one episode of nausea, headache, sore throat, lethargy,
and dizziness at the highest PYY dose.
"We are encouraged by the results of this Phase I-B PYY study since we are
seeing appetite reduction, calorie reduction, even without dietary
intervention or behavioral changes, and a well tolerated safety profile,"
commented Gordon Brandt, M.D., Executive Vice President, Clinical and Medical
Affairs. "Once the Phase I-B and Phase I-C studies are completed and the data
is analyzed we hope to be in a position to advance the program into Phase II
weight loss studies."
In Q4 2003, Nastech reported results of a Phase I-A dose-ranging study
designed to determine the timing and extent of PYY appearance in the blood
stream following intranasal administration. After nasal administration, PYY
was increased in the plasma as early as 5 minutes and reached peak levels at
15 to 20 minutes, simulating the normal release kinetics following a meal. The
peak values increased with rising dose and showed strong dose proportionality.
The highest group-mean PYY plasma levels were over 6-fold higher than the
pre-meal levels measured in this study and significantly above the levels
reported in the literature to occur after eating. The plasma half-life
measured was approximately one hour after nasal administration, which is
similar to what occurs naturally after a meal.
The safety profile of PYY in this Phase I-A study was encouraging. There
was no nasal discomfort and there were no significant vital sign changes in
any subject at any time. Dose-related nausea and lightheadedness was seen
only in subjects with blood levels above a 4-fold increase from baseline.
In February 2004, Nastech initiated a Phase I-C dose-sequencing, double
blind, placebo-controlled, in-clinic study. This study is being conducted
primarily to determine the optimal dosing sequence for PYY, in other words
whether once, twice, or three times a day, and before which meals, achieves
optimal satiety and calorie reduction. The study also is assessing inter- and
intra-subject variability and gender effects on appetite scores, caloric
reduction, pharmacokinetics and safety. This study is expected to be the
final step prior to initiation of Phase II trials.
APOMORPHINE MAXIMUM TOLERATED DOSE STUDY
The MTD study, initiated in June 2003, was designed to determine if
typical apomorphine-related side effects, such as hypotension or low blood
pressure, nausea, vomiting or syncope, the medical term for fainting, occur
with the nasal dosage form and if they do, at what dose they occur. The
multi-center, double blind, placebo-controlled study enrolled 102 men age 50
to 82 years approximately half of whom had erectile dysfunction. The study
involved a single daily active- or placebo-dose administration for seven
consecutive days. Doses began at 0.5 mg and escalated in increments of
0.25 mg. Vital signs were measured both supine and standing to observe
orthostatic effects and ECG measurements were taken during the five hours
after each dose.
Based on the results of this study, doses up to 1.75 mg are safe and well
tolerated and doses up to 2.0 mg are acceptable for further in-clinic safety
studies. Results indicate that there is no clinically or statistically
significant effect on the group means for systolic, diastolic, or mean
arterial blood pressure, supine or standing, at doses up to 2.0 mg nor is
there a trend across dosage groups.
The per event frequency of non-symptomatic systolic hypotension, defined
as a drop of >20 mm Hg divided by the number of measurements taken, was 5% for
the placebo group and 5% to 8% for the apomorphine treatment groups. The per
event frequency of symptomatic hypotension was zero for the placebo and 0% to
1.6% for the apomorphine treatment groups. This is in comparison to the
PDE-5 inhibitors, which are known to cause blood pressure drops in subjects
under similar controlled clinical conditions.
The per event frequency of nausea, defined as the occurrence of nausea
divided by the number of doses given, was 2% or less for all apomorphine
groups up to 1.75 mg and was 6% for the 2.0 mg dosage group. There was no
vomiting in patients receiving less than 2.0 mg and the per event frequency of
vomiting at 2.0 mg was 2%. For perspective, nausea or dyspepsia is the third
most frequent adverse event seen in efficacy trials of sildenafil, a PDE-5
inhibitor, after headache and facial flushing.
The per event frequency of dizziness, defined as the occurrence of
dizziness divided by the number of doses, was 1% to 3% at doses of 0.5 mg to
1.0 mg and was 1% to 5% at doses of 1.25 mg to 2.0 mg.
With respect to ECG changes, the FDA has identified QTc prolongation as a
significant safety concern for all pharmaceuticals, due to the potential to
produce rare but sometimes fatal cardiac arrhythmias. Therefore, QTc
interval, using the Fridericia correction, was measured after all doses in all
patients. There was no prolongation in group mean QTc intervals at any time
after any dose of apomorphine. For perspective, the PD5 inhibitor vardenafil
contains a "precaution" in its product labeling because it was associated with
QTc prolongation during controlled clinical trials.
There was no occurrence of syncope at any time after any dose of
apomorphine in the approximately 700 doses administered in this study.
Syncope occurs with a sublingual formulation of apomorphine and this was a
significant concern for regulatory authorities reviewing that dosage form.
"The substantial safety profile difference between our nasal dosage form
of apomorphine and the sublingual dosage form in apomorphine in clinical
trials to date, as well as its efficacy, is a demonstration of the value
proposition for nasal delivery of apomorphine," stated Steven C. Quay, M.D.,
Ph.D., Chairman, President and Chief Executive Officer of Nastech. "The next
step for this program is to submit this data together with protocols for
further studies to the FDA and to obtain regulatory guidance on a program
intended to permit development, and if successful, approval and marketing of
apomorphine nasal spray for sexual dysfunction."
Steven C. Quay, M.D., Ph.D., Chairman, President and Chief Executive
Officer, will host the Company's 2003 earnings conference call today at
11:00 a.m. Eastern time. Fourth quarter and 2003 financial results as well as
clinical results from the PYY Phase I-B study and apomorphine MTD study will
be discussed during the call. To access the live call or the two-day archive
via the Internet, log on to http://www.Nastech.com. Please connect to the
Company's website at least 15 minutes prior to the conference call to ensure
adequate time for any software download that may be needed to hear the
webcast. We advise turning off any pop-up blockers in order to access the
call via the Internet. Telephone replay is available approximately two hours
after the call through March 17, 2004. To access the replay, please call
800-428-6051 (U.S.) or 973-709-2089 (international). The conference ID number
On March 9, 2004 HHS Secretary Tommy G. Thompson announced a new obesity
national education campaign and a new obesity research strategy at HHS'
National Institutes of Health (NIH). HHS' release of its new education
campaign with the Ad council and NIH research agenda coincided with
publication of the CDC study in this week's Journal of the American Medical
Association. The study, "Actual Causes of Death in the United States, 2000,"
finds that 400,000 deaths in the U.S. (17 percent of all deaths) were related
to poor diet and physical inactivity. "Poor diet and physical inactivity may
soon overtake tobacco as the leading cause of death," the study concludes.
The article is available at http://jama.ama-assn.org. Secretary Thompson
announced that the NIH is developing a Strategic Plan for NIH Obesity
Research. The strategy will intensify research to better understand, prevent
and treat obesity through behavioral and environmental approaches to modifying
lifestyle; pharmacologic, surgical and other medical approaches; and breaking
the link between obesity and diseases such as type 2 diabetes, heart disease
and some forms of cancer. The NIH draft strategic plan is available at
Nastech Pharmaceutical Company Inc. is an emerging pharmaceutical company
developing products based on applying our proprietary drug delivery
technologies, with approximately 195 patents and applications filed. The
Company is developing molecular biology based technologies for delivering both
small and large molecule drugs by nasal administration, along with an extended
release oral delivery technology. The Company's intranasal drug delivery
technology may lead to greater drug efficacy, speed of action, safety, and
patient compliance. Nastech is developing a diverse product portfolio across
multiple therapeutic areas, including products targeted for the treatment of
male and female sexual dysfunction, obesity, pain management, osteoporosis,
and multiple sclerosis. Additional information about Nastech is available at
NASTECH SAFE HARBOR STATEMENT
Statements contained herein that are not historical fact may be
forward-looking statements within the meaning of Section 27A of the Securities
Act of 1933, as amended, and Section 21E of the Securities Exchange Act of
1934, as amended, that are subject to a variety of risks and uncertainties.
There are a number of important factors that could cause actual results to
differ materially from those projected or suggested in any forward-looking
statement made by the Company. These factors include, but are not limited to:
(i) the ability of the Company to obtain additional funding; (ii) the ability
of the Company to attract and/or maintain manufacturing, research, development
and commercialization partners; (iii) the Company's and/or a partner's ability
to successfully complete product research and development, including
pre-clinical and clinical studies and commercialization; (iv) the Company's
and/or a partner's ability to obtain required governmental approvals,
including product and patent approvals; and (v) the Company's and/or the
Company's partner's ability to develop and commercialize products that can
compete favorably with those of competitors. In addition, significant
fluctuations in quarterly results may occur as a result of the timing of
milestone payments, the recognition of revenue from Milestone payments and
other sources not related to product sales to third parties, and the timing of
costs and expenses related to the Company's research and development program.
Additional factors that would cause actual results to differ materially from
those projected or suggested in any forward-looking statements are contained
in the Company's filings with the Securities and Exchange Commission,
including those factors discussed under the caption "Risk Factors" in the
Company's most recent Annual Report on Form 10-K and Quarterly Reports on Form
10-Q, which the Company urges investors to consider. The Company undertakes
no obligation to publicly release the revisions in such forward-looking
statements that may be made to reflect events or circumstances after the date
hereof or to reflect the occurrences of unanticipated events or circumstances,
except as otherwise required by securities and other applicable laws.
SOURCE Nastech Pharmaceutical Company Inc.
/CONTACT: Matthew D. Haines, Director, Corporate Communications of
Nastech Pharmaceutical Company Inc., +1-212-297-6198, firstname.lastname@example.org; or
Aline Schimmel (Investors), or Kathy L. Jones, Ph.D. (Media), +1-212-213-0006,
both of Burns McClellan, for Nastech Pharmaceutical Company Inc./
/Web site: http://www.nastech.com
CO: Nastech Pharmaceutical Company Inc.
IN: HEA MTC BIO
SU: SVY CCA
-- NYW052 --
2978 03/10/2004 07:45 EST http://www.prnewswire.com