CHARLOTTE, N.C., June 19, 2014 (GLOBE NEWSWIRE) -- 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.