positive results for acrux’s lead product

08.05.06
POSITIVE RESULTS FOR
ACRUX’S LEAD PRODUCT
IN US PHASE 3 TRIAL
• Pivotal milestone for Evamist™ and Acrux’s platform technology
• US marketing application to be submitted to FDA by Acrux’s
partner VIVUS in second half of 2006
• VIVUS to pay Acrux US$4 million on submission and approval of
marketing application, followed by royalties on sales
• Annual sales of estrogen-alone therapies in USA $1.4 billion
Melbourne, 8 May 2006: Acrux (ASX: ACR), the pharmaceutical
company with unique technology for delivering drugs through the skin,
today announced positive results in a US Phase 3 clinical trial of
Evamist™, its daily skin spray for prevention of symptoms associated with
menopause. The trial was conducted by its US commercial partner VIVUS
Inc. (NASDAQ: VVUS), which will now proceed to file a marketing
application with the US Food and Drug Administration (FDA) in the
second half of 2006.
Evamist is the most advanced commercial application of Acrux’s patented
delivery technology; if the FDA approves VIVUS’ marketing application,
Acrux’s first product could be available to women in the USA in the
second half of 2007. Several other products that use the same delivery
technology are following close behind. The positive result of this Phase 3
trial is therefore a pivotal milestone for each of these products.
The Phase 3 trial assessed the safety and efficacy of Evamist for the
treatment of hot flushes in menopausal women. The trial was a 12-week
study of 457 menopausal women, conducted under a Special Protocol
Assessment (SPA) from the FDA. Results showed that the most effective
Evamist dose decreased the number of hot flushes by 78%. The reduction
in frequency and severity of moderate to severe hot flushes was statistically
significant compared with placebo for all three doses of Evamist evaluated.
Importantly, application site irritation was less than 1% and was mild in nature. The
results from the trial will be discussed by VIVUS at an Analyst Day in New York on
18 May 2006.
“We believe these positive trial results along with this novel patient-preferred
transdermal delivery system will establish Evamist as a superior estrogen therapy
for the treatment of menopausal symptoms,” stated Leland Wilson, president and
chief executive officer for VIVUS. “We have worked diligently toward the
development of this unique and easy-to-use product, and we are thrilled with the
efficacy and safety demonstrated in this trial. We now look forward to filing an
NDA for Evamist in the second half of 2006.”
Professor Alastair MacLennan, Joint Editor-in-Chief of Climacteric, the Journal of
the International Menopause Society, and a member of Acrux’s Scientific Advisory
Board, commented “Evamist could provide an attractive new option for millions of
women - a low dose estrogen, delivered in a simpler and more convenient way.
These Phase 3 trial results demonstrate its efficacy in treating the key symptoms that
may be suffered by this significant patient group”.
Acrux’s partnership with VIVUS
VIVUS licensed Evamist for the US market from Acrux in February 2004. VIVUS
paid Acrux a licence fee of US$1 million and will make further payments to Acrux
totalling US$4 million on filing and approval by the FDA of the US marketing
application. VIVUS is responsible for manufacturing, sales and marketing in the
USA and will pay Acrux royalties on sales. Acrux retains rights for the rest of the
world and is seeking commercial partners for major markets, including Europe.
Menopause and Evamist
Approximately two million American women turn 50 each year. Women naturally
enter into menopause usually between the ages of 45 and 55; however, surgical
menopause may happen at any age. Menopausal symptoms occur when the ovaries
stop producing estrogen. Symptoms include hot flushes, discomfort or pain during
sexual intercourse due to vaginal atrophy (thinning of the vagina), and changes in
skin and hair. Annual sales of estrogen-only replacement therapies in the USA are
estimated to be approximately US$1.4 billion. Sales have now resumed growth
after a period of decline, as new data from the Women’s Health Initiative study
showed that estrogen-alone therapy resulted in no increased risk of coronary heart
disease or breast cancer. Transdermal estrogen patches and gels currently sell
approximately US$0.3 billion per annum. Primary market research studies suggest
that many women would prefer to use Evamist over patches, gels and tablets.
Evamist, like Acrux’s other women’s health products addressing contraception and
decreased libido, is a small, hand-held, easy-to-use spray that is designed to provide an
easy and convenient means to deliver a preset dose of estradiol, a naturally occurring
estrogen, via the skin. Evamist is placed gently against the skin and an actuator button
is pushed, which releases a light spray containing a proprietary formulation of
estradiol. Estradiol is released into the blood stream on a sustained basis over 24
hours, providing a practical and convenient once-a-day dosing regimen. Evamist is
fast drying, non-irritating and invisible after application. Studies have shown that
once administered, Evamist’s formulation is not affected by washing and does not
transfer to partners. Evamist is easily titratable between one, two and three sprays.
About Acrux www.acrux.com.au
�� Acrux is a specialty pharmaceutical company, developing and
commercialising a range of patented, patient-preferred healthcare products for
global markets, using its innovative technology to administer drugs through
the skin.
�� Fast-drying, invisible sprays or liquids provide a delivery platform with low
or no skin irritation, superior cosmetic acceptability and simple, accurate and
flexible dosing. The technology platform is covered by broad and welldifferentiated
patents issued and pending in major markets.
�� Acrux has 7 products in clinical development, including:
o Evamist™ to treat menopause symptoms
o Testosterone MDTS® to treat decreased libido in women
o Nestorone® MDTS® contraceptive spray for women
o Fentanyl UDTS™ to treat chronic pain
o Testosterone MD-Lotion® to treat testosterone deficiency in men
�� Acrux has licensed USA rights for Evamist™ (Estradiol MDTS®) and
Testosterone MDTS® to VIVUS and AUS/NZ distribution rights for
Testosterone MDTS® and Fentanyl UDTS™ to CSL Limited. Acrux has also
licensed its technology to Lilly for veterinary healthcare products.
About VIVUS
VIVUS, Inc. is a pioneer in the research and development of proprietary products to
restore sexual function for women and men. VIVUS' current product pipeline
includes four investigational products in late stage clinical development. For
women, VIVUS has completed a Phase 3 program for Evamist™ for the alleviation
of menopausal symptoms, and initiated a Phase 2B program with ALISTA™ for
female sexual arousal disorder. Additionally, the company has completed Phase 2
development of Testosterone MDTS® for the treatment of hypoactive sexual desire
disorder (HSDD). The MDTS system is a patented new-generation, transdermal
drug delivery technology that delivers drugs directly through the skin. For men,
VIVUS has completed Phase 2 development of avanafil for erectile dysfunction.
The company currently markets MUSE® (alprostadil) suppository for the treatment
of erectile dysfunction in the U.S. and internationally through distributors. For more
information on clinical trials and products, please visit the company's web site at
www.vivus.com.
Contacts:
Igor Gonda, Acrux CEO & Managing Director
+61 3 8379 0100; [email protected]
Alastair Maclennan, Professor of Obstetrics & Gynaecology, The University of
Adelaide +61 8 8161 7000
Appendix 1 – Trial details
Name of trial A Phase 3 Multi-Centre, Randomised,
Double-Blind, Placebo-Controlled Study to
Evaluate the Safety and Efficacy of Estradiol
Metered-Dose Transdermal Spray (Evamist)
in the Treatment of Vasomotor Symptoms in
Postmenopausal Women
Treatment method, route,
frequency, dose levels
Daily application to the skin of either one,
two, or three sprays of Evamist for 12 weeks
Number of trial subjects 457 subjects at 43 clinical sites in the USA
Subject selection criteria Postmenopausal women with a mean total
frequency of ≥ 56 moderate to severe hot
flushes per week
Control group Daily application to the skin of either one,
two, or three sprays of placebo for 12 weeks
Primary endpoint(s) results: The most effective Evamist dose significantly
decreased the number of hot flashes by 78%,
from 10.7 hot flushes per day at baseline to
2.3 hot flushes after treatment. The decrease
was statistically significant compared with
placebo (p<0.0001). The reduction in
frequency and severity of moderate to severe
hot flashes was statistically significant over
placebo for all three doses of Evamist
evaluated.
Safety and tolerability Application site irritation was less than 1%
and was mild in nature