Droxidopa Development Overview
Northera™ (droxidopa)* is an oral synthetic amino acid prodrug that crosses the blood-brain barrier and is converted both peripherally and centrally into norepinephrine. Because the converting enzyme, aromatic amino acid decarboxylase, is widely expressed throughout the body, administration of droxidopa is thought to replenish norepinephrine even if postganglionic sympathetic neurons are not intact.
Chelsea Therapeutics acquired the global development and commercialization rights to droxidopa (L-DOPS) from Dainippon Sumitomo Pharma Co., Ltd. in 2006, excluding Japan, Korea, China and Taiwan. Since that time we have conducted multiple clinical trials investigating the safety and efficacy of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension (nOH), our lead indication.
Symptomatic nOH occurs in patients with underlying neurodegenerative disorders such as Parkinson’s disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF). Treatment of nOH often poses a clinical challenge for clinicians since there is only one FDA approved medication and this option is associated with significant adverse events. Additionally, to date, this medication has been unable to demonstrate that it improves the symptoms (dizziness / lightheadedness) associated with this disorder. Clinicians often have to resort to using off-label treatments to help manage their patients’ nOH symptoms.
We believe Northera™ has the potential to be the first safe and effective drug that will treat symptomatic nOH without leading to significant supine hypertension, thereby improving the quality of life for patients suffering from this disorder. If approved, we believe, Northera™ will offer a significant advancement for patients relative to their current treatment options.
In January 2007, the FDA granted orphan drug status** for droxidopa for the treatment of nOH in patients with primary autonomic failure (PD, MSA, and PAF), dopamine-ß-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Later that same year, the drug was granted orphan medicinal product designation by the European Medicines Agency (EMA) for the treatment of patients with PAF and patients with MSA.
To date, we have completed three Phase III studies evaluating the efficacy and safety of Northera™ in the treatment of symptomatic nOH (Studies 301, 302, and 306). Additionally, we have completed two long term open-label extensions studies (Studies 303 and 304), a comprehensive thorough QTc study, and a 24-hour ambulatory blood pressure monitoring safety study (Study 305). Collectively, these data show that Northera™ significantly improves dizziness / lightheadedness (cardinal symptom of nOH) and appears to be safe and well tolerated.
The data generated through our nOH clinical development program is the foundation for Northera’s New Drug Application (NDA) resubmission that was sent to the FDA on August 14, 2013. The FDA has informed Chelsea that Northera will be reviewed by the Cardiovascular and Renal Drug Advisory Committee (CRDAC) and the meeting is tentatively scheduled for January 14, 2014. Northera’s Prescription Drug User Fee Act (PDUFA) goal date is February 14, 2014.
*Droxidopa is an investigational new drug not currently marketed in North America and the European Community. No claims on the safety and efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension are being made, implied, or intended by the resources contained here within.
**Orphan Drug Status is granted for rare diseases afflicting less than 200,000 patients per year in the United States and a similar population in Europe. Orphan designation provides us with seven years of marketing exclusivity in the United States and ten years in the European Union.