Contact:
Glenn L. Cooper, M.D.
President and CEO
Contact at Interneuron:
William B. Boni
VP, Corp. Communications
(781) 402-3410
LEXINGTON, MA, August 17, 1998 -- Interneuron Pharmaceuticals, Inc.
(NASDAQ: IPIC) today announced results of a Phase 2/3 trial showing
that treatment with pagoclone, a novel GABA receptor modulator,
statistically significantly reduced the frequency of panic attacks
among patients suffering from panic disorder. In addition, pagoclone
was well-tolerated by these patients, with no evidence of sedation and
no apparent withdrawal symptoms in this study, which included a
tapering-off period. Based on the results of this trial, Interneuron
has identified an optimal dose of pagoclone for Phase 3 clinical testing.
The double-blind, placebo-controlled, parallel group study involved 277
patients at six clinical sites in the U.S. Patients were enrolled in the
study following confirmed diagnoses of panic disorder. The number of attacks
experienced by each patient during a two-week screening period prior to
enrollment represented the baseline for subsequent comparison of panic attack frequency.
Following the screening period, patients were randomized to receive one of
three doses of pagoclone orally (.15 milligrams/day, .30 milligrams/day or .60 milligrams/day)
or placebo for eight weeks. The primary outcome measurement was the
change from baseline in the number of panic attacks seen at the eight week time point.
This primary analysis, conducted on a last observation carried forward (LOCF)
basis, showed that patients in the .15 milligrams/day group experienced a 42
percent reduction in the number of panic attacks relative to patients on
placebo (p=0.141), that patients in the .30 milligrams/day group experienced
a 73 percent reduction relative to patients on placebo (p=0.021), and that
patients in the .60 milligrams/day group experienced a 52 percent reduction
(p=0.098) relative to patients on placebo.
Pagoclone was extremely well tolerated with a low incidence of side
effects in all dosage groups and no clinically significant differences
from placebo. Sedation, a major liability of benzodiazepine drugs,
was evaluated by use of the Stanford Sleepiness Scale. There were
no differences observed between pagoclone and placebo using this
scale. In addition, there were no evident withdrawal effects seen
at the end of the study as determined by the Rickels Withdrawal Scale. Of
note, other common side effects seen with existing classes of anti-anxiety
drugs were not significantly different between pagoclone patients and
patients receiving placebo in this trial. These traditional side effects
include sedation, lack of mental acuity, withdrawal and rebound anxiety
related to the benzodiazepine class of drugs, and agitation, insomnia and
sexual dysfunction related to serotonin reuptake inhibitors.
Full results of this trial will be submitted for presentation at an
upcoming meeting of the American College of Neuro-Psychopharmacology (ACNP).
"We are pleased that this trial successfully achieved its objectives,"
said Glenn L. Cooper, M.D., president and chief executive officer of
Interneuron. "The study demonstrated that pagoclone statistically
significantly reduced panic attacks, and it provides dose-response
data identifying an optimal dose that allows us to proceed with the
remainder of Phase 3 clinical testing. It is notable that the .30
milligrams/day dose was the minimally effective dose and that the higher
dose did not confer additional benefit. Furthermore, the study demonstrated
an excellent safety profile for pagoclone that differentiates this novel
agent from older benzodiazepines and newer serotonin reuptake inhibitors."
The results of this study support findings from the Company's previous
Phase 2 double-blind placebo-controlled cross-over clinical trial,
conducted in the U.K. These findings showed that the .30 milligrams/day
dose produced a statistically significant reduction in the total number of
panic attacks among 16 patients over a two week treatment period
and a reduction in the average number of panic attacks per day
compared to the pre-treatment period. No significant change
in the total number of panic attacks was observed during placebo
treatment in this earlier trial, and the drug was well tolerated
with no evidence of sedation or withdrawal effects.
Panic disorder is a severe anxiety condition characterized by
panic attacks, acute episodes of anxiety comprised of distressing
symptoms, such as difficulty breathing, sweating, heart palpitations,
feeling dizzy or faint, and fear of losing control. There are approximately
2.5 million patients in the U.S. with panic disorder and over 20 million
patients with anxiety disorders.
Anxiety disorders, including panic disorder, are believed to be
associated with excessive neuronal activity resulting from a decrease
in the function of the major inhibitory neurotransmitter called GABA
(gamma amino butyric acid). Pagoclone, a member of the cyclopyrrolone
class of compounds that is believed to modulate GABA neurotransmission,
may normalize the action of GABA in the brain, thereby reducing the
excessive neuronal activity associated with anxiety and panic attacks.
A particular benefit of such a GABA modulator is a reduction in the
propensity for unwanted side effects, such as sedation and withdrawal.
Interneuron licensed worldwide rights to pagoclone from Rhône-Poulenc
Rorer (RPR) in 1994 in exchange for licensing, milestone and royalty payments to RPR.
Interneuron Pharmaceuticals is a diversified biopharmaceutical
company engaged in the development and commercialization of a portfolio
of products and product candidates primarily for neurological and
behavioral disorders. Interneuron is also developing products and
technologies, generally outside the central nervous system field,
through three subsidiaries: Intercardia, Inc. focused on cardiovascular
disease and carbohydrate-based drug discovery; Progenitor, Inc. focused
on developmental genomics; and InterNutria, Inc. focused on dietary supplement products.
