Next-Generation GRII Receptor Antagonist Prevents/Reverses Weight Gain Linked To Olanzapine Use - Active Ingredient In Zyprexa(R)

Corcept Therapeutics
Incorporated (NASDAQ: CORT) announced results from two
preclinical studies conducted as part of its collaboration with Eli
Lilly. The data demonstrate that CORT 108297 has the potential to
both reduce weight gain caused by olanzapine and to prevent weight
gain caused by initiation of treatment with olanzapine. Olanzapine
is the active ingredient in Lilly's Zyprexa(R), which is indicated
for the treatment of schizophrenia and bipolar disorder.



The two studies were conducted in a rat model of olanzapine induced
weight gain. The data confirmed results previously reported from
similar studies of CORLUX, Corcept's late-stage GRII receptor
antagonist, which the company is evaluating in two ongoing Phase 3
trials for psychotic depression and Cushing's Syndrome.



"We are encouraged by these preclinical results which confirm results
we have seen previously in both rat and human studies with CORLUX,
another compound in this class," said Dr. Robert L. Roe, M.D.,
President of Corcept. "The use of GRII antagonists to prevent weight
gain commonly associated with the use of many antipsychotic drugs
could be of great benefit to the millions of people currently taking
these medications. We believe that the effect of CORLUX on Zyprexa
associated weight gain will extend to other antipsychotic medications
and are currently conducting a prevention of Risperdal(R) induced
weight gain study in healthy men to test this hypothesis."



CORT 108297 Demonstrated Statistically Significant Weight Control





-- Study Design: Six groups (n = 12 per group) of rats were allowed to
eat a normal diet for 56 days. Five groups were dosed orally with
olanzapine daily. The sixth group received placebo. At day 35, the five
groups receiving olanzapine had gained a statistically significant amount
of weight compared to the group receiving placebo. The five olanzapine
groups then began to receive daily oral doses either of CORT 108297 (at one
of three dose levels), CORLUX, or placebo through day 56.


-- Results: The rats administered olanzapine alone continued to gain
weight through day 56. In contrast, the rats given olanzapine along with
CORT 108297 and those administered olanzapine with CORLUX did not. By day
56, there was a highly statistically significant difference between these
groups and the group administered olanzapine alone. In addition,
olanzapine induced weight gain amelioration by CORT 108297 was dose
dependent. The rats that received the combination of olanzapine with CORT
108297, or with CORLUX, had significantly less abdominal fat than the group
dosed with olanzapine alone.


















CORT 108297 Demonstrated Statistically Significant Weight Gain
Prevention




-- Study Design: Six groups (n = 12 per group) of rats were allowed to
eat a normal diet for 21 days. Five groups were dosed orally with
olanzapine daily and one group was given placebo daily. Four of the groups
that received olanzapine were also dosed orally with either CORT 108297 (at
one of three dose levels) or CORLUX; one group received olanzapine plus
placebo. The sixth group was dosed with only placebo.


-- Results: At day 21, the three groups dosed with the combination of
olanzapine and CORT 108297 had gained significantly less weight compared to
the group administered olanzapine alone. Rats administered olanzapine plus
CORLUX also gained less weight than rats administered olanzapine alone, but
this result did not reach statistical significance.





Atypical Antipsychotics Are All Known to Cause Weight Gain



The labels of the following atypical antipsychotic class drugs
contain a warning for hyperglycemia and diabetes mellitus, both
associated with the weight gain seen in many patients taking the
following drugs:



Abilify(R) (aripiprazole, Bristol Myers Squibb and Otsuka American
Pharmaceutical)


Clozaril(R) (clozapine, Novartis)


Geodon(R) (ziprasidone, Pfizer)


Risperdal(R) (risperidone, Janssen, a unit of Johnson & Johnson)


Seroquel(R) (quetiapine, AstraZeneca)


Zyprexa(R) (olanzapine, Eli Lilly).


Despite their side effect profile, atypical antipsychotic medications
are widely prescribed throughout the world because of their efficacy.



About Corcept Therapeutics Incorporated



Corcept is a pharmaceutical company engaged in the development of
drugs for the treatment of severe psychiatric and metabolic
disorders. The company has two Phase 3 programs ongoing; CORLUX for
the treatment of the psychotic depression and for Cushing's Syndrome.



Corcept has also developed an extensive intellectual property
portfolio that covers the use of GRII antagonists in the treatment of
a wide variety of psychiatric and metabolic disorders, including the
prevention of weight gain caused by the use of antipsychotic
medication. The company has also discovered and filed patents for
the three different series of compounds which block cortisol's
activity at the GRII receptor but do not block the progesterone
receptor. CORT 108297, a potential lead compound from these series,
recently produced encouraging results in a human microdosing study.
The compound was extremely well absorbed, demonstrated good
bioavailability and had a half-life that appears compatible with
once-a-day oral dosing. Corcept retains worldwide commercial rights
to CORT 108297 as well as all additional compounds within the three
series. corcept



Statements made in this news release, other than statements of
historical fact, are forward-looking statements, including, for
example, statements relating to Corcept's clinical development and
research programs. Forward-looking statements are subject to a number
of known and unknown risks and uncertainties that might cause actual
results to differ materially from those expressed or implied by such
statements. For example, there can be no assurances with respect to
the cost, rate of spending, completion or success of clinical trials;
financial projections may not be accurate; there can be no assurances
that Corcept will pursue further activities with respect to the
development of CORLUX, CORT 108297, or any of its other selective
GR-II antagonists. These and other risk factors are set forth in the
Company's SEC filings, all of which are available from our website
(corcept) or from the SEC's website (sec). We
disclaim any intention or duty to update any forward-looking
statement made in this news release.

corcept


View drug information on Ziprasidone; Zyprexa.