Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today
announced the publication in Neurology of its pivotal, Phase 3
study 301, a multicenter, multinational, double-blind, randomized,
placebo-controlled, parallel-group study of NORTHERATM (droxidopa)
that details how NORTHERA demonstrated a statistically significant
difference in efficacy compared to placebo for improving the
symptoms of neurogenic orthostatic hypotension (NOH).
NORTHERA was approved by the U.S. Food and Drug Administration
on February 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.
Data from pivotal study 301, published online ahead of print in
Neurology, was used to support the safety and efficacy of NORTHERA
as part of its new drug application.
"Droxidopa, a norepinephrine prodrug, is the first treatment
approved in 20 years for symptomatic neurogenic orthostatic
hypotension, a syndrome characterized by blunted noradrenergic
response to standing," said lead author Horacio Kaufmann, M.D.,
Professor of Neurology and Medicine at New York University and
Director of the Dysautonomia Center at NYU Langone Medical Center.
"In a double-blind randomized trial, 7-day treatment with droxidopa
was superior to placebo in relieving symptoms and was associated
with an increase in standing systolic blood pressure."
"Neurogenic orthostatic hypotension is a rare and debilitating
condition associated with neurogenic disorders such as Parkinson's
Disease and multiple system atrophy, that is often overlooked and
underdiagnosed," said Joseph G. Oliveto, President and CEO of
Chelsea. "The publication of our 301 study in Neurology, a highly
respected medical journal, adds to the peer-reviewed literature on
NOH and will help increase understanding of NOH among
physicians."
The trial examined the efficacy and safety of droxidopa versus
placebo. The primary endpoint was the relative improvement in mean
Orthostatic Hypotension Questionnaire (OHQ) composite score
following 1 week of treatment. The OHQ is a validated, NOH-specific
tool assessing symptom severity and symptom impact on daily
activities as reported by patients. When evaluating the OHQ
composite, it was found that droxidopa-treated patients improved by
0.90 units (p=0.003), compared to placebo.
The OHQ may be divided into two independently validated
composite sub scores. The orthostatic hypotension symptom
assessment composite (OHSA), which examines a variety of symptoms,
and the orthostatic hypotension daily activities assessment
composite (OHDAS), which examines a variety of symptom impacts.
Improvement in the OHSA composite score favored droxidopa by 0.73
units (p=0.010). The largest improvement in an individual symptom
item was recorded for item 1 (dizziness/lightheadedness) which
favored droxidopa by 1.30 units (p<0.001). Improvement in OHDAS
composite favored droxidopa by 1.06 units (p=0.003), with the
largest individual item change recorded for "ability to conduct
activities that require standing a long time" which favored
droxidopa by 1.30 units (p=0.001)
A biologically relevant correlate for efficacy, the mean change
in standing systolic blood pressure (BP) increased by 11.2 vs 3.9
mmHg (p<0.001). An important safety observation was the change
in the mean supine systolic BP by 7.6 vs 0.8 mmHg (p<0.001)
study. There were relatively few patients who experienced BP
increases above180 mmHg: 4.9 percent of droxidopa and 2.5 percent
of placebo recipients.
Overall, this short-term multicenter trial showed that droxidopa
treatment was associated with significant improvement in multiple
symptoms of NOH and of NOH impact on activities requiring standing
or walking as well as an associated increase in standing systolic
BP. Furthermore, these benefits were associated with an acceptable
safety profile.
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 NORTHERATM (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
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