Message #1 From:
Jason Date: June 21, 2007 05:23:39 PM
MDVN, Medivation's Dimebon(TM) Maintains Statistically Significant Benefit on All Five Efficacy Endpoints in Alzheimer's Disease Trial After One Year of Therapy
- Aggregate Benefit over Placebo Larger at One Year than at Six Months -
- Dimebon-Treated Patients Stabilized for a Full Year -
- Conference Call Scheduled for Today at 8:30 a.m. Eastern Time -
SAN FRANCISCO and WASHINGTON, June 11 /PRNewswire-FirstCall/ --
Medivation, Inc. (Nasdaq: MDVN) today announced that the benefits of Dimebon
over placebo in its double-blind, placebo-controlled Phase 2 study in mild-to-
moderate Alzheimer's disease were statistically significant on all five study
endpoints at 12 months. Importantly, on every endpoint studied, the benefits
of Dimebon over placebo at one year were stable or greater when compared to
benefits at six months. Dimebon patients were stabilized over the one year
study period, meaning that their level of function was preserved for a full
year on all five endpoints. The endpoints spanned all of the most frequently
studied aspects of Alzheimer's disease: cognition, overall clinical function,
activities of daily living, and behavioral problems. Dimebon was well
tolerated throughout the entire one-year treatment period.
On the study's primary endpoint, the ADAS-cog, Dimebon caused an
improvement over placebo of 6.9 points at one year (observed case analysis;
p<0.0001). On the global function endpoint used in this study, the CIBIC-
plus, Dimebon's benefit over placebo was 0.8 points at 12 months (observed
case analysis; p=0.006). Global function improved or remained stable in 69
percent of treated Alzheimer's disease patients after one year of Dimebon
therapy. The ADAS-cog and the CIBIC-plus are the two endpoints the U.S. Food
and Drug Administration has used to approve all currently marketed drugs for
mild-to-moderate Alzheimer's disease.
Dimebon produced an aggregate benefit over placebo in this study that was
larger at 12 months than at six. After a year of treatment Dimebon's benefit
over placebo was greater than six-month levels on the ADAS-cog (6.9 points vs.
4.0 points), the CIBIC-plus (0.8 points vs. 0.6 points), and the ADCS-ADL (5.2
points vs. 2.9 points); however, only the ADAS-cog difference reached
statistical significance (observed case analysis; p=0.006). Dimebon's benefit
over placebo on the other two endpoints (the MMSE and the NPI) at six months
was maintained at one year.
Jeffrey Cummings, MD, the Augustus Rose Professor of Neurology at the
University of California, Los Angeles, and Director of the UCLA Alzheimer's
Disease Center stated: 'I consider these efficacy data to be noteworthy
because they show an overall treatment benefit that is consistent, robust and
larger at twelve months than at six. To my knowledge, this is the first
randomized, double-blind, placebo-controlled study in which statistically
significant benefit was achieved on endpoints measuring each of the four most
clinically relevant aspects of mild-to-moderate Alzheimer's disease after a
full year of therapy. Given these data and the fact that Dimebon was well
tolerated in this study, I consider Dimebon one of the most promising
Alzheimer's disease compounds in development.'
'The natural history of untreated Alzheimer's disease includes decline in
thinking abilities, social behavior and function,' observed Rachelle Doody,
MD, PhD, the Effie Marie Cain Chair in Alzheimer's Disease Research at the
Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine in
Houston, and principal investigator of this study. 'By contrast, after a full
year of therapy Dimebon-treated patients did not decline in any of these
areas. These data demonstrate that, as a group, Dimebon-treated patients
stabilized for a full year, whereas placebo-treated patients declined at the
expected rate.'
Dimebon-treated patients experienced significantly fewer serious adverse
events than placebo-treated patients (3.4 percent vs. 11.7 percent,
respectively; p=0.03) and dropped out of the study at a rate (31.5 percent)
consistent with the dropout rate in the placebo group (37.2 percent). The most
frequently reported adverse events associated with treatment were dry mouth
(18.0 percent incidence), depressed mood/depression (14.6 percent incidence)
and sweating (5.6 percent incidence). These adverse events generally were
mild in severity and did not result in study discontinuation.
'These strongly positive one-year results further support and validate our
results at six months,' commented David Hung, MD, president and chief
executive officer of Medivation. 'We are quite encouraged to have shown a
further increase in Dimebon's statistically significant benefit over placebo
at 12 months, a treatment period twice as long as is required for
registration, in a disease characterized by progressive deterioration. We
remain on target to begin our six-month Phase 3 clinical studies of Dimebon in
Alzheimer's disease next year.'
The 12 month Dimebon data will be presented at 10:00 a.m. Eastern Time on
Tuesday, June 12, at the 2nd Alzheimer's Association International Conference
on Prevention of Dementia in Washington, D.C. (abstract # S3-02-03, 'Results
of a One-Year Randomized, Placebo-Controlled Trial of Dimebon for the
Treatment of Mild to Moderate Alzheimer's Disease'). In addition, the
Alzheimer's Association has selected the Dimebon data for inclusion in a news
briefing on Alzheimer's disease therapies to be held at 12:00 p.m. Eastern
time today.
Dimebon Trial Design
In the multi-center, double-blind trial, 183 patients with mild to
moderate Alzheimer's disease were randomized to oral Dimebon, 20 mg three
times a day (60 mg/day), or placebo for six months. Of these patients, 134
subsequently consented to continue treatment for up 12 months in the same
treatment group to which they were originally randomized, and 120 (or 90
percent) of the continuing patients completed the study.
The trial included five efficacy endpoints that assessed the four most
commonly studied aspects of Alzheimer's disease progression - cognition (the
Alzheimer's Disease Assessment Scale-cognitive subscale, or ADAS-cog; and the
Mini Mental State Exam, or MMSE), overall clinical function (the Clinician's
Interview-Based Impression of Change with a caregiver interview, or
CIBC-plus), activities of daily living (the Alzheimer's Disease Cooperative
Study Group-Activities of Daily Living, or ADCS-ADL), and behavioral problems
(the Neuropsychiatric Inventory, or NPI). The study was conducted at multiple
sites in Russia.
Dimebon Trial Six-Month Results
Medivation previously announced six-month results, showing that Dimebon-
treated patients demonstrated significant improvement on the primary endpoint
of ADAS-cog (p<0.0001) and the key secondary endpoint of CIBIC-plus (p<0.0001)
compared with patients receiving placebo. Dimebon-treated patients also
significantly outperformed the placebo-treated patients (p<0.01) on the three
additional secondary endpoints: the ADCS-ADL, the NPI and the MMSE.
Teleconference/Webcast Details
Medivation will host a teleconference at 8:30 a.m. Eastern time today to
discuss the data. To participate in the live call by telephone, please dial
800-565-5442 from the U.S. or 913-312-1298 internationally. A telephone
replay will be available for seven days following the conclusion of the call
by dialing 888-203-1112 from the U.S. or 719-457-0820 for international
callers and entering passcode 4782383. Individuals interested in listening to
the live call via webcast may do so by visiting http://www.medivation.com. A
replay of the webcast will be available on the Company's website for 30 days.
About Dimebon
Dimebon, the Company's lead product candidate, is an orally-available
small molecule that has been shown to inhibit brain cell death in preclinical
models relevant to Alzheimer's disease and Huntington's disease, making it a
potential treatment for these and other neurodegenerative diseases. Based on
the clinical and preclinical data generated to date, Medivation believes that
Dimebon operates by a novel mechanism of action and may exert a
neuroprotective effect in multiple areas of the central nervous system.
Dimebon appears to block a new target that involves mitochondrial pores, which
are believed to play a role in the cell death that is associated with
neurodegenerative diseases and the aging process.
Medivation is currently evaluating Dimebon in both Alzheimer's and
Huntington's diseases. The Company expects to enter global Phase 3 studies of
Dimebon in Alzheimer's disease in 2008 and, assuming positive data, to submit
marketing applications in the U.S. and Europe in 2010 for this indication. In
Huntington's disease, the Company is currently evaluating Dimebon in a Phase
1-2a clinical trial in collaboration with the Huntington Study Group.
About MDVN Medivation
Medivation, Inc. is a biopharmaceutical company that acquires promising
technologies in the late preclinical development phase and develops them
quickly and cost-effectively. Medivation's current portfolio consists of
small molecule drugs in development to treat three large, unmet medical needs
- Alzheimer's disease, Huntington's disease and hormone-refractory prostate
cancer. The Company intends to build and maintain a portfolio of four to six
development programs at all times. For more information, please go to
http://www.medivation.com.
