-First Presentation of Integrated Data
Analyses From Two Pivotal Trials
-Data Shows Statistically Significant
Improvement in Symptoms of NOH vs. Placebo
Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today
announced the presentation of an integrated analysis of data from
two pivotal multicenter, placebo-controlled, randomized clinical
trials showing that NORTHERA™ (droxidopa) had demonstrated an
acceptable safety profile and demonstrated a statistically
significant difference in efficacy compared to placebo for
improving the symptoms of neurogenic orthostatic hypotension (NOH)
in a population comprised chiefly of patients with Parkinson's
Disease (PD). The results were presented at the 18th International
Congress of Parkinson's Disease and Movement Disorders (MDS) in
Stockholm, Sweden, June 8-12, 2014.
NORTHERA was approved by the U.S. Food and Drug Administration
on Feb. 18, 2014, for the treatment of orthostatic dizziness,
lightheadedness, or the "feeling that you are about to black out"
in adult patients with symptomatic neurogenic orthostatic
hypotension caused by primary autonomic failure (Parkinson's
disease, multiple system atrophy, and pure autonomic failure),
dopamine beta-hydroxylase deficiency, and non-diabetic autonomic
neuropathy. Effectiveness beyond 2 weeks of treatment has not been
demonstrated. The continued effectiveness of NORTHERA should be
assessed periodically. Symptomatic NOH is an orphan condition that
affects an estimated 80,000 to 150,000 patients in the United
States. As part of its New Drug Application, Chelsea submitted data
from pivotal studies 301 and 306 in support of the safety and
efficacy of NORTHERA. For MDS, data from these studies were
integrated, analyzed and presented together, marking the first time
these data were presented at a major medical meeting. MDS draws
more than 4,000 physicians and medical professionals from more than
80 countries to view more than 1,600 scientific abstracts submitted
by clinicians from around the world.
The posters, titled Integrated Efficacy of Droxidopa for
Neurogenic Orthostatic Hypotension and Integrated Safety of
Droxidopa for Neurogenic Orthostatic Hypotension, were presented at
the Parkinson's disease dysautonomia Poster Session at MDS.
"Overall, 359 patients contributed data to the integrated
efficacy analyses, 174 randomized to droxidopa and 185 to placebo.
Patients on NORTHERA self-reported more improvements in NOH
symptoms of dizziness/lightheadedness, feeling faint or the
'feeling that you are going to black out' compared to patients on
placebo," said Robert A. Hauser, MD, Professor of Neurology,
Molecular Pharmacology, and Physiology, and Director of the
Parkinson's Disease and Movement Disorders Center, University of
South Florida. "Patients on NORTHERA also showed improvements in
standing systolic blood pressure at one week compared to patients
on placebo."
Dr. Hauser was the lead author on the integrated efficacy
poster.
Horacio Kaufmann, MD, Professor of Neurology and Medicine at New
York University and Director of the Dysautonomia Center at NYU
Langone Medical Center, was the lead author on the safety poster.
"Droxidopa demonstrated an acceptable safety profile across these
two pivotal induction design trials in patients in NOH, and data
shows that adverse events were consistent across studies 301 and
306 and consistent with other studies of droxidopa," he said.
About Studies 301 And 306
In Study 301, adult patients with symptomatic NOH due to primary
autonomic failure (PD, MSA, or PAF), DBH, or NDAN underwent an
up-to-2-week titration of open-label droxidopa, so as to identify
their optimal dose. Responders underwent a 7-day washout, followed
by a 7-day double-blind trial of optimized treatment versus placebo
(100–600 mg TID). In Study 306, adult PD patients with symptomatic
NOH underwent an up-to-2-week titration of double-blind droxidopa
or placebo, followed by an 8-week double-blind trial of maintenance
treatment (100–600 mg TID).
In both studies, safety assessments included adverse-event (AE)
monitoring. Blood pressure was assessed multiple times using the
Orthostatic Standing Test (OST). Supine hypertension was defined as
a systolic pressure >180 mmHg at all three observations during
the 10-minute supine period of the OST. During the supine period,
patients had their head and torso elevated at an angle of
approximately 30 degrees.
Efficacy assessments were made at randomization and the end of
week one of double-blind study-drug treatment, using the
Orthostatic Hypotension Questionnaire (OHQ) comprised of the
six-item Orthostatic Hypotension Symptom Assessment (OHSA) and the
four-item Orthostatic Hypotension Daily Activity Scale (OHDAS).
Data on standing systolic blood pressure was collected at all
study-site visits when each subject had stood for three minutes
after having been supine for 10 minutes.
Efficacy Results
Overall, data from 359 subjects, including 263 with underlying
Parkinson's disease, contributed to the integrated efficacy
analyses. For analyses of subjects' self-ratings on OHSA Item 1
("dizziness/lightheadedness, feeling faint, or feeling like you
might black out," on average over the preceding week), data from
174 droxidopa and 185 placebo recipients (including 127 and 136
with underlying PD) were analyzed. From randomization to the end of
double-blind Week 1, the mean score change was –2.5 ±3.1 versus
–1.3 ±2.9 units (p<0.001) and 55.2 percent versus 35.1 percent
of the subjects had improvements of greater than 50 percent
(p<0.001). The proportions of subjects with improvements of ≥1,
≥2, ≥3, or ≥4 units were also significantly greater among droxidopa
recipients than among placebo recipients.
For standing systolic blood pressure analyses, data from 173
patients on droxidopa and 184 patients on placebo were analyzed.
From randomization to the end of double-blind Week 1, the mean
change was +8.6 ±20.5 versus +0.9 ±18.5 mmHg (p<0.001). The
proportions of subjects with increases of ≥5, ≥10, ≥15, or ≥20 mmHg
were also significantly greater among droxidopa recipients than
among placebo recipients.
Safety Results
During double-blind treatment, the overall incidence of reported
adverse events was 18.5 percent for patients on droxidopa versus
14.8 percent for patients on placebo in Study 301 for up to 1-week
exposure, and 79.8 percent versus 80.6 percent, respectively, in
Study 306 up to 10-week exposure. Headache was the only type of AE
that was reported in greater than 5 percent of patients from both
trials while on double-blind droxidopa or placebo. In study 301,
7.4 percent of patients on droxidopa reported headaches compared to
0 on placebo; and in study 306, 13.2 percent of patients on
droxidopa reported headaches compared to 7.4 percent of patients on
placebo.
During study-drug titration, the overall incidence of reported
AEs was 38 percent for open-label droxidopa in study 301, 55.3
percent for double-blind droxidopa in study 306, and 43.5 percent
for double-blind placebo in study 306.
Across the studies, 5.6 percent of the pooled droxidopa group
(11 of 195) and 3.2 percent of the pooled placebo group (6 of 189)
had a systolic blood pressure >180 mmHg at all 3 observations
during a 10-minute supine period.
About symptomatic neurogenic orthostatic hypotension
(NOH)
It is estimated that 80,000 to 150,000 patients suffer from
symptomatic NOH in the U.S. Symptomatic NOH is a chronic disorder
that is caused by an underlying neurogenic disorder, such as
Parkinson's disease, multiple system atrophy or pure autonomic
failure. Symptoms of NOH may include dizziness, lightheadedness,
blurred vision, fatigue, poor concentration, and fainting episodes
when a person assumes a standing position. These symptoms can
severely limit a person's ability to perform routine daily
activities that require standing or walking for both short and long
periods of time.
About NORTHERA (droxidopa)
NORTHERA is the first and only therapy approved by the FDA that
demonstrates symptomatic benefit in adult patients with NOH caused
by primary autonomic failure (Parkinson's disease, multiple system
atrophy and pure autonomic failure), dopamine beta hydroxylase
deficiency and non-diabetic autonomic neuropathy. NORTHERA is
expected to be launched in the second half of 2014.
NORTHERA carries a boxed warning for supine hypertension. The
most common adverse events experienced in controlled studies were
headache, dizziness, nausea, hypertension and fatigue. Please see
NORTHERA full Prescribing Information at
www.chelseatherapeutics.com, and Important Safety Information
below.
The NORTHERA approval was granted under the FDA's accelerated
approval program, which allows for conditional approval of a
medicine that fills a serious unmet medical need, provided
additional confirmatory studies are conducted. The package insert
indicates that effectiveness beyond two weeks of treatment has not
yet been demonstrated; therefore the continued effectiveness of
NORTHERA in patients should be assessed periodically. A
multi-center, placebo-controlled, randomized study, which is
designed with the goal of definitively establishing the durability
of the clinical benefits of NORTHERA, has been preliminarily agreed
to with the FDA.
IMPORTANT SAFETY INFORMATION
WARNING: SUPINE HYPERTENSION
See full prescribing information for complete boxed warning.
Monitor supine blood pressure prior to and during treatment and
more frequently when increasing doses. Elevating the head of the
bed lessens the risk of supine hypertension, and blood pressure
should be measured in this position. If supine hypertension cannot
be managed by elevation of the head of the bed, reduce or
discontinue NORTHERA.
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Supine Hypertension: NORTHERA therapy may cause or exacerbate
supine hypertension in patients with NOH, which may increase
cardiovascular risk if not well-managed.
Hyperpyrexia and Confusion: Postmarketing cases of a symptom
complex resembling neuroleptic malignant syndrome (NMS) have been
reported in Japan with NORTHERA use. Observe patients carefully
when the dosage of NORTHERA is changed or when concomitant levodopa
is reduced abruptly or discontinued, especially if the patient is
receiving neuroleptics. NMS is an uncommon but life-threatening
syndrome characterized by fever or hyperthermia, muscle rigidity,
involuntary movements, altered consciousness, and mental status
changes. The early diagnosis of this condition is important for the
appropriate management of these patients.
Ischemic Heart Disease, Arrhythmias, and Congestive Heart
Failure: NORTHERA therapy may exacerbate symptoms in patients with
existing ischemic heart disease, arrhythmias, and congestive heart
failure.
Allergic Reactions: This product contains FD+C Yellow No. 5
(tartrazine) which may cause allergic-type reactions (including
bronchial asthma) in certain susceptible persons. Although the
overall incidence of FD+C Yellow No. 5 (tartrazine) sensitivity in
the general population is low, it is frequently seen in patients
who also have aspirin hypersensitivity.
ADVERSE REACTIONS
The most common adverse reactions (greater than 5 percent) were
headache, dizziness, nausea, hypertension, and fatigue.
DRUG INTERACTIONS
Administering NORTHERA in combination with other agents that
increase blood pressure (e.g., norepinephrine, ephedrine,
midodrine, and triptans) would be expected to increase the risk for
supine hypertension; Dopa-decarboxylase inhibitors may require dose
adjustments for NORTHERA.
USE IN SPECIAL POPULATIONS
Clinical experience with NORTHERA in patients with severe renal
function impairment (GFR less than 30 mL/min) is limited; There are
no adequate and well controlled trials of NORTHERA in pregnant
women; Women who are nursing should choose nursing or NORTHERA; The
safety and effectiveness of NORTHERA in pediatric patients have not
been established; No overall differences in safety or effectiveness
were observed between subjects aged 75 years and older, and younger
subjects in clinical trials, but greater sensitivity of some older
individuals cannot be ruled out.
About Chelsea Therapeutics
Chelsea Therapeutics (Nasdaq:CHTP) is a biopharmaceutical
development company that acquires and develops innovative products
for the treatment of a variety of human diseases, including central
nervous system disorders. Chelsea acquired global development and
commercialization rights to droxidopa (L-DOPS), or NORTHERA, from
Dainippon Sumitomo Pharma Co., Ltd. in 2006, excluding Japan,
Korea, China and Taiwan. For more information about the Company,
visit www.chelseatherapeutics.com.
As previously announced, pursuant to the Agreement and Plan of
Merger, dated as of May 7, 2014 (Merger Agreement), by and among
Chelsea, H. Lundbeck A/S (Lundbeck), and Charlie Acquisition Corp.,
an indirect wholly owned subsidiary of Lundbeck (Acquisition Sub),
Lundbeck has commenced a tender offer (Offer) to purchase all of
the outstanding shares of Chelsea. Lundbeck and Acquisition Sub
have filed a tender offer statement on Schedule TO (as amended, the
Schedule TO), including an offer to purchase, a letter of
transmittal and related documents, with the Securities and Exchange
Commission (SEC), and Chelsea has filed a
Solicitation/Recommendation Statement on Schedule 14D-9 (as
amended, the Statement) with respect to the Offer. The Offer will
only be made pursuant to the offer to purchase, the letter of
transmittal and related documents filed as a part of the Schedule
TO. Subject to Acquisition Sub's irrevocable acceptance for payment
in the Offer of at least a majority of Chelsea's common stock
outstanding on a fully diluted basis and to the satisfaction or
waiver of certain other customary conditions, Acquisition Sub will
merge with and into Chelsea (Merger) and, subject to certain
exceptions, each Chelsea share not tendered in the Offer will be
cancelled and converted into the right to receive in the Merger the
same consideration per share paid in the Offer.
Safe Harbor/Forward-Looking Statements
The above information contains forward-looking statements,
including without limitation statements regarding the planned
completion of the Offer and the Merger.
Some of these forward-looking statements may contain words like
"believe," "may," "could," "would," "might," "possible," "will,"
"should," "expect," "intend," "plan," "anticipate," or "continue,"
the negative of these words, or other terms of similar meaning or
they may use future dates. These statements are subject to risks
and uncertainties that could cause actual results and events to
differ materially from those anticipated, including, but not
limited to, risks and uncertainties related to: the timing of the
transaction; diversion of the attention of Chelsea's management
away from Chelsea's day-to-day business operations; the percentage
of Chelsea's stockholders tendering their shares in the Offer; the
possibility that competing offers will be made and the effects of
provisions in the Merger Agreement that could discourage or make it
difficult for competing offers to be made; the possibility that
various closing conditions for the transaction may not be satisfied
or waived, including that a governmental entity may prohibit, delay
or refuse to grant approval for the consummation of the
transaction; the effects of disruption caused by the transaction
making it more difficult to maintain relationships with employees,
collaborators, vendors and other business partners; stockholder
litigation in connection with the transaction resulting in
significant costs of defense, indemnification and liability; and
other risks and uncertainties discussed in Chelsea's filings with
the SEC, including the "Risk Factors" sections of Chelsea's Annual
Report on Form 10-K for the year ended December 31, 2013 and
Quarterly Report on Form 10-Q for the quarter ended March 31, 2014,
as well as the Statement and the tender offer documents filed by
Lundbeck and Acquisition Sub. Chelsea undertakes no obligation to
update any forward-looking statements as a result of new
information, future developments or otherwise, except as expressly
required by law. All forward-looking statements in this document
are qualified in their entirety by this cautionary statement.
CONTACT: Media:
David Connolly
LaVoieHealthScience
617.374.8800 ext 108
dconnolly@lavoiehealthscience.com
Investors:
David Pitts
Argot Partners
212-600-1902
david@argotpartners.com
Chelsea Therapeutics International, Ltd. (MM) (NASDAQ:CHTP)
Gráfico Histórico do Ativo
De Ago 2024 até Set 2024
Chelsea Therapeutics International, Ltd. (MM) (NASDAQ:CHTP)
Gráfico Histórico do Ativo
De Set 2023 até Set 2024