open label......
Thursday July 20, 8:12 am Eastern Time
Company Press Release
Neurocrine Announces Publication Reporting First
Clinical Evidence of Efficacy of CRF Receptor
Antagonists in Patients With Major Depression
Improvement of Depressive Symptoms in Approximately 80% of Treated Patients Revealed in
Journal of Psychiatric Research
SAN DIEGO--(BW HealthWire)--July 20, 2000-- Neurocrine Biosciences (Nasdaq: NBIX - news) today announced the
publication of the first human clinical experience in patients with major depressive disorder utilizing a corticotropin-releasing
factor1 (CRF1) receptor antagonist, NBI 30775, also known as R121919 which has been developed in collaboration with
Janssen Pharmaceutica.
Results from this landmark study showed that NBI 30775 was well tolerated, did not exhibit endocrinological side effects and
demonstrated significant anti-depressant activity defined by reduction in Hamilton Depression Scores. The study reported was
an open label Phase IIa clinical trial performed at the Max Planck Institute of Psychiatry in Munich under the direction of Dr.
Florian Holsboer and published in the Journal of Psychiatric Research (Vol. 34, no. 3, pages 171-181).
``This is a very important study because it is the first to document the beneficial effect of CRF receptor antagonists in reducing
major depression,'' noted Florian Holsboer, M.D., Ph.D, Director, Max Planck Institute of Psychiatry. ``Many of the patients
we have treated with NBI 30775 have experienced remarkable improvement with this new approach.''
``These findings provide strong evidence for the hypothesis that CRF1 receptor antagonists will have therapeutic potential in the
treatment of neuropsychiatric disorders such as anxiety and depression, and may also prove efficacious in disorders where
exaggerated central CRF activity is present either at baseline or following stress exposure,'' added Holsboer.
In this study NBI 30775 was administered to 20 patients with major depressive episodes. The patients were enrolled in two
open label dose-escalation panels: one group where the dose range increased from 5-40mg and another group where the dose
escalated from 40 to 80mg. The drug was administered once a day for 30 days and patients were monitored for safety and
tolerability particularly related to effects on the stress hormone system. Additionally, antidepressant and anti-anxiety efficacy
measurements were performed utilizing the Hamilton Depression and Anxiety Scores (HAMD and HAMA) and patient Beck
Depression Index (BDI) rating scales.
Results from the trial, as reported in the Journal of Psychiatric Research, showed that the compound was found to be safe and
well tolerated in all patients throughout the 30 day test period. Blockade of CRF1 receptors did not impair secretory activity of
the stress hormones, corticotropin and cortisol, either during treatment or following exogenously administered CRF. These
safety results support the hypothesis that suppression of the stress hormone system is not required to produce efficacy with this
novel mechanism. Treatment response, as defined by more than a 50% reduction in HAMD was seen in 50% of the patients in
the low dose group and 80% of the patients in the higher dose group. Anxiety reductions of equal proportion were also seen in
these patients. Furthermore a majority of patients experienced a rebound effect or return of depressive symptoms following
cessation of therapy, further suggesting therapeutic benefit of this therapy.
``Of all the novel agents studied for the treatment of depression, the CRF receptor antagonists are the most promising and have
the greatest likelihood of success. This is because of the vast data base which has documented CRF hyper secretion in
depression,'' stated Charles B. Nemeroff, M.D., Ph.D., Reunette W. Harris Professor and Chairman Department of
Psychiatry, Emory University School of Medicine.
While NBI 30755 was found to be safe in this study, in another study, reversible increases in liver enzymes were observed in
two volunteers participating in an expanded safety trial conducted in the United Kingdom. As a result Janssen Pharmaceutica
announced its decision to discontinue development of R121919 in favor of a back-up compound resulting from its expanded
collaboration with Neurocrine. Approximately 250 subjects to date have been treated in various clinical trials with no other
observed safety issues.
Neurocrine is also developing an unpartnered CRF antagonist compound for anxiety/depression and plans to initiate clinical
trials with its proprietary compound in the 2nd half 2000. ``We are excited about these data which validate years of preclinical
efficacy results generated by our scientists and collaborators from around the world,'' stated Gary Lyons, President & CEO.
``This work brings us one step further toward definitive validation of this novel mechanism for the treatment of psychiatric
disorders. It is our goal to remain the world leader in the CRF field and we have increased our R&D efforts to rapidly bring the
next generation of these compounds into clinical trials.''
Depression and anxiety disorders afflict over 100 million patients worldwide every year. Existing anti-depressant and
anti-anxiety therapeutics sell in excess of $8 billion worldwide, but there remains significant unmet medical needs. Fifteen million
Americans will experience a major depressive illness at some time in their lives. Depression is the leading cause of suicide,
which claims more than 30,000 lives each year in the U.S. The market for these combined indications is dominated by a class
of compounds called selective serotonin reuptake inhibitors (SSRIs) such as Prozac®, Paxil® and Zoloft®. The SSRIs are
effective two-thirds of the time, leaving significant room for improved therapeutics. Two major drawbacks of the SSRIs are the
delayed onset of action and sexual dysfunction associated with the use of this class of therapeutics. These drugs often require
3-6 weeks of treatment to take effect, if at all, an eternity for a severely depressed patient. A rapid acting anti-depressant
would be a major advance in the treatment of this devastating disease.
Normal brain functions rely on appropriate levels of the neurotransmitter corticotropin-releasing factor (CRF). In
neuropsychiatric disorders such as Depression and Anxiety, CRF levels are dramatically increased in the central nervous
system. It has long been hypothesized that blockade of this neurohormone may be beneficial in the treatment of such disorders.
CRF was first identified and cloned by Neurocrine co-founder, Dr. Wylie Vale and his colleagues at the Salk Institute.
Neurocrine holds the patent rights to the CRF family of receptors and has developed multiple series of selective, potent, small
molecule antagonists for these receptors. CRF functions as a neurotransmitter in the brain and plays a critical role in
coordinating the body's responses to stress. The CRF1 receptor subtype largely mediates these effects. In preclinical models,
selective CRF1 receptor antagonists block stress responses providing evidence that this novel mechanism may result in
improved anti-anxiety and anti-depressant drugs. CRF1 antagonists have not shown evidence of sexual dysfunction or addictive
properties in preclinical models. In addition, some data suggest that CRF1 antagonists may have a more rapid onset of action
compared to the currently marketed anti-depressants.
Neurocrine has now advanced five programs into clinical trials. The company is conducting several Phase II trials with
NBI-34060 for insomnia, a Phase I/II with NBI 3001 for glioblastoma and a Phase I with NBI 6024 with Altered Peptide
Ligand for Type I diabetes. In addition, Neurocrine is planning a Phase II clinical trial of its APL compound for multiple
sclerosis following positive results from an earlier Phase II trial.
Neurocrine Biosciences is a leading neuroscience company focused on the discovery and development of novel therapeutics for
neuropsychiatric, neuroinflammatory and neurodegenerative diseases and disorders. The Company's neuroscience, endocrine
and immunology disciplines provide a unique biological understanding of the molecular interaction between central nervous,
immune and endocrine systems for the development of therapeutic interventions for anxiety, depression, insomnia, stroke,
malignant brain tumors, multiple sclerosis, obesity and diabetes.
Neurocrine Biosciences, Inc. news releases are available through the Company's website via the Internet at
neurocrine.com. In addition to historical facts, this press release may contain forward-looking statements that
involve a number of risks and uncertainties. Among the factors that could cause actual results to differ materially from those
indicated in the forward looking statements are risks and uncertainties associated with Neurocrine's CRF antagonist
development programs including, but not limited to, risks and uncertainties associated with, or arising out of, clinical
development of products including risk that development candidates, will not successfully proceed through early clinical trials or
that in later stage clinical trials will not show that they are effective in treating humans; determinations by regulatory and
governmental authorities, uncertainties relating to patent protection and intellectual property rights of third parties; impact of
competitive products and technological changes; availability of capital and cost of capital; and other material risks. A more
complete description of these risks can be found in the Company's Form 10K for December 31, 1999. Neurocrine undertakes
no obligation to update the statements contained in this press release after the date hereof.
Contact:
Neurocrine Biosciences
Claudia Jones or Paul Hawran, 858/658-7600 |
