|NORTHERA(TM) Clinical Trial Data Published in Neurology; Recent Scientific Discoveries May Reflect Well on Placenta-Based Cell Therapies|
|By Staff and Wire Reports|
|Thursday, 19 June 2014 20:00|
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.
For an organ that only functions for nine months, the placenta has been taking the science world by storm. It recently garnered front page coverage in the New York Times, when a newly published study showed that a placenta’s bacterial population may help shape the health of the infant by influencing the bacterial makeup of its gut. The bacteria that normally colonize the human intestines can affect metabolism and perhaps also the risk for obesity and diabetes.
In another recent report in the journal, Molecular Human Reproduction, it was shown that the placenta may be central to the process that causes female babies to be more likely to have better outcomes after preterm birth, lower rates of stillbirth and neonatal death, and better health outcomes overall as compared to male babies.
These two new findings show that the placenta is more central to infant development and health then was originally recognized, reflecting well on the idea of using placental cells for treating diseases. In fact, just last month, the U.S. National Institutes of Health (NIH) announced the establishment of the Human Placenta Project, which seeks to improve understanding of the placenta and its role in human health and development. The following statement is made on the NIH’s site regarding the impetus for the Human Placenta Project:
The placenta is the least understood human organ and arguably one of the more important, not only for the health of a woman and her fetus during pregnancy but also for the lifelong health of both. To address this lack of knowledge, the NICHD believes a concerted effort, the Human Placenta Project, would make substantial inroads.
Other multi-disciplinary projects established by the NIH to expand knowledge about a distinct topic include the Human Genome Project and the Human Connectome Project. According to a study published last year, the Human Genome Project created a $966 billion economic impact, and has led to new diagnostics, drugs and a rapidly expanding genetics industry.
One company that is banking on the therapeutic powers of the placenta is Haifa, Israel-based Pluristem Therapeutics, a key player in the regenerative medicine space. Pluristem takes cells from donated human placentas, which are generally discarded after birth, and expands and modulates them in 3-dimensional bioreactors using proprietary technology.
The therapeutic cells produced in Pluristem’s manufacturing facility are injected into muscle where they secrete proteins which could potentially treat certain cardiovascular diseases, muscle and tendon injuries and preeclampsia, one of the leading known causes of premature births, stillbirths and early neonatal and maternal deaths. According to the World Health Organization, preeclampsia occurs in approximately 6%–8% of pregnancies worldwide. It is estimated that preeclampsia costs the global health care system $3 billion annually.
“Pluristem long ago recognized the importance of the placenta as a source of immuno-privileged therapeutic cells that can be administered without matching. We have conducted extensive pre-clinical and clinical research into the functioning and mechanism of action of placental cells, and their therapeutics potential” stated Pluristem CEO Zami Aberman. “We applaud the NIH’s efforts to spur further studies of the placenta. A greater understanding of this very unique organ can open new pathways for therapeutics based on placental cells for numerous diseases including preeclampsia.”
“As a global leader in placental cell therapies, it is rewarding for us to see a growing recognition of the role the placenta plays in human health, and we are pleased to be a key contributor to scientific knowledge and advancements that can lead to important new therapies,” said Dr. Karine Kleinhaus, Pluristem’s Divisional Vice President for North America.
The company is gearing up Phase II and phase III trials in the cardiovascular and muscle injury indications and expects to begin a phase I study in preeclampsia in late 2014.
Aldeyra Therapeutics, Inc. (Nasdaq:ALDX), a biotechnology company focused on the development of products to treat diseases related to free aldehydes, today announced that Stephen Tulipano has joined Aldeyra as its Chief Financial Officer, effective June 23, 2014.
athenahealth, Inc.(Nasdaq:ATHN), a leading provider of cloud-based services for electronic health record (EHR), practice management, and care coordination, today announced that its clients account for 59.2 percent of providers across the U.S. who have successfully attested to Stage 2 of the Meaningful Use EHR incentive program as of May 31, 2014.
Capricor Therapeutics, Inc. (OTCBB:CAPR), a biotechnology company focused on developing novel therapeutics for the treatment of cardiovascular diseases, today announced that Dr. Rachel Ruckdeschel Smith, Ph.D., Vice President of Research and Development at Capricor, participated in a panel discussion on the regulation of therapeutic products derived from human stem cells at the DIA 2014 50th Annual Meeting, being held June 15-19, 2014 in San Diego, California.
Cellular Biomedicine Group, Inc. (Nasdaq:CBMG) today released the six-month follow-up data analysis of its Phase I/IIa clinical trial for its Rejoin™ human adipose-derived mesenchymal precursor cell (haMPC) therapy for Knee Osteoarthritis (KOA).
Galena Biopharma, Inc. (Nasdaq:GALE), a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major unmet medical needs to advance cancer care, today announced that Mark W. Schwartz, Ph.D., Executive Vice President and Chief Operating Officer will present a corporate update at the 9th Annual JMP Securities Healthcare Conference.
Integra LifeSciences Holdings Corporation (Nasdaq:IART), a world leader in medical technology, today announced that June 2014 marks the 25th anniversary of its founding.
MacroGenics, Inc. (Nasdaq:MGNX), a clinical-stage biopharmaceutical company focused on discovering and identifying innovative monoclonal antibody-based therapeutics for the treatment of cancer and autoimmune disease, today announced that a first patient received drug in a Phase 1 study of MGD006 in relapsed or refractory acute myeloid leukemia (AML).
Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced that it has reached an agreement with Sanofi to regain worldwide rights to develop and commercialize MM-121, a monoclonal antibody designed to block ErbB3 (HER3) activation in patients with heregulin-positive tumors and improve response to standard of care treatments.
Novavax, Inc. (Nasdaq:NVAX), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of recombinant nanoparticle vaccines and adjuvants, announced today a number of promotions within its management team.
Prosensa Holding N.V. (NASDAQ: RNA) today announced that Hans Schikan, Chief Executive Officer, will present a corporate overview at the JMP Securities Healthcare Conference in New York, NY.
Relypsa, Inc. (Nasdaq:RLYP), a biopharmaceutical company, today announced the election of Daniel K. Spiegelman, executive vice president and chief financial officer of BioMarin Pharmaceutical Inc., and Kenneth J. Hillan, president and chief executive officer of Achaogen, Inc., to its board of directors following the company's annual meeting of stockholders held earlier today.
StemCells, Inc. (Nasdaq:STEM) reported positive interim results from its Phase I/II clinical trial of the Company's proprietary HuCNS-SC® human neural stem cell platform in dry age-related macular degeneration (AMD) yesterday evening at the 12th annual meeting of the International Society for Stem Cell Research (ISSCR) in Vancouver, Canada.
Vascular Solutions, Inc. (Nasdaq:VASC) today announced the U.S. market launch of its Gel-Bead embolization spheres for the treatment of hypervascular tumors.