AEterna Zentaris Announces Results from Two Phase 3 Studies with Cetrorelix in Benign Prostatic Hyperplasia
QUEBEC CITY, Aug. 17 /PRNewswire-FirstCall/ - AEterna Zentaris
Inc. (NASDAQ: AEZS; TSX: AEZ) (the "Company"), a global
biopharmaceutical company focused on endocrine therapy and
oncology, today reported Phase 3 results for its North American
efficacy trial Z-033 and the safety trial Z-041 in benign prostatic
hyperplasia (BPH), with its lead endocrinology compound for
urology, cetrorelix pamoate. As announced on March 6, 2009,
sanofi-aventis U.S. LLC entered into an agreement with terna
Zentaris for the development, registration and marketing of
cetrorelix in BPH for the U.S. market.
The first multi-center efficacy trial Z-033 was conducted in 53
sites in the United States and Canada, with 8 additional sites in
Europe. The study involved 667 patients under the supervision of
lead investigator, Herbert Lepor, M.D., Professor and Chairman,
Department of Urology, at NYU School of Medicine, New York.
Patients entered a 1- to 4-week screening period to confirm
severity and stability of voiding symptoms based on the
International Prostate Symptom Score (IPSS). Patients were then
randomly allocated to cetrorelix or placebo in a double-blind
fashion. Patients were administered cetrorelix by intra-muscular
(IM) injection at Week 0, 2, 26 and 28 (for treatment Arm A, those
in Arm B received IM injection at week 0, 2 and 26 followed by
placebo at Week 28). Patients in treatment Arm C received placebo
injections at Week 0, 2, 26 and 28. All patients were followed up
to Week 52.
The study Z-033 demonstrated no clear differences in overall
efficacy with all 3 groups showing an improvement in IPSS of
approximately 4 points that was maintained throughout the 52 weeks.
There was a slight advantage in favor of the main active treatment
arm (Arm A) up to Week 46 of the follow-up, which was no longer
demonstrated at Week 52. These differences did not achieve
statistical significance. Furthermore, a favorable trend on the
IPSS, as compared to placebo, was seen in a sub-group of patients
with large prostate glands (greater than 50 cm3) on entry to the
Tolerability of cetrorelix in study Z-033 was very good, as
evidenced by the absence of major differences to placebo with
regard to both clinical adverse events or changes in laboratory
parameters. The most frequently reported adverse experiences
included hot flushes, nasopharyngitis, injection site pain, and
headache, which is what was seen in the safety study Z-041. In
particular, the incidence of hot flushes was lower than was seen in
study Z-041 (see below), and they were also reported by patients
randomized to placebo.
In the safety study Z-041, all patients received cetrorelix by
intra-muscular (IM) injection at Weeks 0 and 2, and were followed
up to Week 26. The primary endpoint was the incidence of possibly
drug-related adverse events; efficacy parameters were evaluated as
secondary endpoints. The study was conducted in 68 sites in the
United States and Canada.
Cetrorelix was generally well tolerated. Adverse events were
mostly mild and transient in intensity. Serious adverse events
occurred in 12 patients, but none of these was assessed as possibly
drug-related. The most frequently reported adverse experiences
included hot flushes, nasopharyngitis, injections site pain, and
headache. Hot flushes were reported by 49 patients and were mild
and of short duration in the majority of patients. Only one patient
experienced a severe episode. A questionnaire was used to assess
the local tolerance of the IM injection and affirmed the
acceptability of this route of administration.
Efficacy was assessed using the IPSS which showed an improvement
from a mean score of 21.2 at baseline to 15.6 at Week 26. In 63% of
the patients, the improvement was by at least 3 points. Notably,
the 46% of patients who had received previous treatment for BPH
showed an important mean improvement of 5 points, which is only
slightly less than the 6 point improvement seen in treatment-na ve
patients. Maximum uroflow improved by 25%, from 10.3 to 12.5
ml/sec, and also the mean uroflow showed similar improvement.
Juergen Engel, Ph.D., terna Zentaris President and CEO stated,
"Although the data received for the open-label safety study Z-041
with a nearly 6 point reduction in IPSS are in line with what we
had observed in our Phase 2 program, we are disappointed by the
failure to achieve the primary endpoint in the efficacy study
Z-033. We remain committed to the ongoing Phase 3 program with
cetrorelix in BPH and are working towards receiving the results of
the second pivotal efficacy study Z-036 in November."
Herbert Lepor, M.D., Professor and Chairman, Department of
Urology, at NYU School of Medicine, New York and Lead Investigator
of the Z-033 trial added, "These findings are unexpected in light
of the previous Phase 2 experience. Those data and the strength of
the safety data available to date had given us confidence in this
potential new treatment for BPH. It is now important to await
results of the other placebo-controlled efficacy study
The Company will host a conference call and webcast to discuss
these results later today, Monday, August 17, 2009 at 10:00 a.m.,
Participants may access the live webcast via the Company's
website at www.aezsinc.com in the "Investors" section, or by
telephone using the following numbers: (outside Canada):
800-588-4942. (Canada): 416-644-3426 or 514-807-8791. A replay of
the webcast will also be available on the Company's website for a
period of 30 days.
About the Phase 3 Program with Cetrorelix in BPH
Cetrorelix pamoate is currently in three Phase 3 trials
involving more than 1,600 patients with symptomatic BPH in Canada,
the United States and Europe.
The first Phase 3 efficacy trial Z-033, titled, "Cetrorelix
pamoate intermittent IM dosage regimens in patients with
symptomatic BPH: a 1-year placebo-controlled efficacy study and
long-term safety assessment", involved 667 patients mostly in North
America and assessed an intermittent dosage regimen of cetrorelix
as treatment for BPH-related signs and symptoms.
As announced recently, patients completing the 52 week
double-blind study are then allowed to continue into an open-label
extension of this study, sponsored by sanofi-aventis, where
patients receive the same dosing regimen of cetrorelix by IM
injection at Week 52, 54, 78 and 80, and are followed up to Week
90. Patients entering this extension study will be followed-up for
safety, IPSS and quality of life, thus providing follow-up data on
cetrorelix for up to 5 years.
The second multi-center Phase 3 efficacy study Z-036 for which
patient recruitment was completed in October 2008, involves 420
patients, mainly in Europe. Patients in this randomized
placebo-controlled study with open-label extension conducted under
the supervision of lead investigator, Prof. Frans M.J. Debruyne,
M.D., of the Andros Mannenkliniek, Arnhem, The Netherlands, receive
cetrorelix according to similar dosing regimens used in the first
efficacy study Z-033.
The primary endpoint for both North American and European
efficacy studies is absolute change in IPSS between baseline and
Week 52. Other efficacy endpoints include additional measures of
BPH symptom progression and the need for BPH-related surgery.
Safety endpoints include changes in sexual function. Other
important endpoints include plasma changes in levels of
testosterone, and assessment of other adverse events.
The third trial of the program is the safety study Z-041 titled,
"Cetrorelix pamoate in patients with symptomatic BPH: an
open-labeled safety and efficacy assessment study". It is a
multi-center, open-label, single-armed study involving 528 patients
in North America. The lead investigator was Joel Kaufman, M.D.,
Associate Clinical Professor in Urology at University of Colorado
School of Medicine in Denver, Colorado and at Urology Research
Options in Aurora, Colorado.
Results of the second efficacy trial Z-036 are scheduled to be
disclosed during the fourth quarter of this year.
Cetrorelix pamoate is an investigational agent that has shown in
Phase 2 studies to provide fast and long lasting relief of BPH
symptoms and was well tolerated, with a low incidence of sexual
side effects. Cetrorelix is part of terna Zentaris' luteinizing
hormone-releasing hormone (LHRH) antagonist therapeutic approach.
This peptide-based active substance was developed by the Company in
cooperation with Nobel Prize winner Prof. Andrew Schally, currently
of the U.S. Veterans Administration in Miami.
Cetrorelix acetate is marketed under the brand name
Cetrotide(R), the first LHRH antagonist approved for therapeutic
use as part of in vitro fertilization programs (controlled
ovulation stimulation/assisted reproductive technologies) in
Europe, the USA and Japan. It was launched on the market through
Serono (now Merck Serono) in the U.S., Europe and in several other
countries, as well as in Japan through Shionogi.
About Benign Prostatic Hyperplasia
Benign prostatic hyperplasia (BPH) is one of the most common
diseases of aging men - affecting more than 20 million men in the
United States - but its etiology is far from being completely
understood. Data from ongoing research suggest BPH and lower
urinary tract symptoms (LUTS) are more complex conditions than once
thought. While previous research on BPH etiology tended to focus on
testosterone and other hormones, more recent research suggests
other factors - including inflammation, various growth factors, and
adrenoreceptors - actually may play a greater role in the
development of BPH and LUTS.
BPH is associated with LUTS, including: frequent urination, a
sudden, uncontrollable urge to urinate, waking at night to urinate
(nocturia), difficulty starting a urine stream (hesitancy and
straining), decreased strength of the urine stream (weak flow),
feeling that the bladder is not completely empty, an urge to
urinate again soon after urinating and pain during urination
(dysuria). Currently available therapies may improve symptoms to
some degree, but often come with sexual and other side
About terna Zentaris Inc.
terna Zentaris Inc. is a global biopharmaceutical company
focused on endocrine therapy and oncology, with proven expertise in
drug discovery, development and commercialization. News releases
and additional information are available at www.aezsinc.com.
This press release contains forward-looking statements made
pursuant to the safe harbor provisions of the U.S. Securities
Litigation Reform Act of 1995. Forward-looking statements involve
known and unknown risks and uncertainties, which could cause the
Company's actual results to differ materially from those in the
forward-looking statements. Such risks and uncertainties include,
among others, the availability of funds and resources to pursue R D
projects, the successful and timely completion of clinical studies,
the ability of the Company to take advantage of business
opportunities in the pharmaceutical industry, uncertainties related
to the regulatory process and general changes in economic
conditions. Investors should consult the Company's quarterly and
annual filings with the Canadian and U.S. securities commissions
for additional information on risks and uncertainties relating to
the forward-looking statements. Investors are cautioned not to rely
on these forward-looking statements. The Company does not undertake
to update these forward-looking statements. We disclaim any
obligation to update any such factors or to publicly announce the
result of any revisions to any of the forward-looking statements
contained herein to reflect future results, events or developments
except if we are required by a governmental authority or applicable
Source: AETERNA ZENTARIS INC.
CONTACT: Investor Relations: Ginette Valli res, Investor
Coordinator, (418) 652-8525 ext. 265, firstname.lastname@example.org; Media Relations:
Paul Burroughs, Director of Communications, (418) 652-8525 ext. 406,
Posted: August 2009