Chelsea Therapeutics International, Ltd.,a biopharmaceutical development company, has announced the results from an integrated dataset of two phase III studies, Study 301 and Study 302, which showed that patients treated with Northera (droxidopa) experienced improvements in their symptoms of Neurogenic Orthostatic Hypotension (also known as NOH or Neurogenic OH) as measured by the Orthostatic Hypotension Questionnaire (OHQ) composite score (p=0.001) and a number of individual symptoms, including dizziness (p=0.004).

These results were presented by Christopher Mathias, MD at the 16th International Congress of Parkinson's Disease and Movement Disorders in Dublin, Ireland.

The results, which include data from over 250 patients with symptomatic Neurogenic OH and diagnoses of Parkinson's disease, multiple system atrophy (MSA), pure autonomic failure (PAF), dopamine beta hydroxylase deficiency or nondiabetic autonomic neuropathy.

Investigators also presented data from a number of subgroups of patients from this integrated dataset.

Gregor Wenning, MD presented data showing that patients with pure autonomic failure and MSA showed statistically significant improvement in the OHQ composite score following droxidopa treatment versus placebo (p=0.022 and p=0.018, respectively). The data also showed that age is an important contributor to improvements seen in patients with Parkinson's disease. Parkinson's disease patients younger than 65 treated with droxidopa showed greater improvements versus placebo than those over 75 (1.63 units vs. -0.04 units).

Phillip Low, MD presented data from a post-hoc analysis which showed that 94 patients taking midodrine at screening presented with more severe condition at baseline as measured by OHQ composite score (6.7 vs. 5.8), yet after treatment with droxidopa, all patients had improvement in OHQ regardless of previous midodrine use. Those patients previously taking midodrine had lesser improvement in OHQ scores compared to placebo than those not previously taking midodrine. Among the patients taking midodrine at screening, there was a significantly higher incidence of supine hypertension (SBP > 200mmHg) compared with after the washout period (8.5 per cent vs. 0 per cent). When treated with droxidopa, these patients experienced a lower incidence of supine hypertension (SBP > 200mmHg) at the end of the study compared to while on midodrine (3.3 per cent vs. 8.5 per cent).

“When we look at the combined data from Study 301 and Study 302, one of the largest combined datasets in this rare condition, there continues to be clear evidence of the efficacy of droxidopa in patients with symptomatic Neurogenic OH,” commented Christopher Mathias, MBBS DPhil DSc FRCP FMedSci, Professor of Neurovascular Medicine at Imperial College London and University College London, University of London. “We see that many of these patients responded well to droxidopa treatment and may now be able to resume various activities in daily life that they previously were incapable of carrying out.”

Additional data from Dr Mathias' integrated analysis showed that droxidopa-treated patients experienced improvements in their symptoms of Neurogenic OH as measured by the Orthostatic Hypotension Symptom Assessment (OHSA) score (p=0.007); 3 of the 6 items of the OHSA (dizziness, p=0.004; weakness, p=0.004; fatigue, p=0.013); the Orthostatic Hypotension Daily Activity Scale (OHDAS) composite score (p < 0.001); and all 4 individual items of the OHDAS (standing a short time, p=0.001; standing a long time, p < 0.001; walking a short time, p=0.004; walking a long time, p=0.009). Treatment with droxidopa showed low rates of supine hypertension.

Robert Hauser, MD presented a preliminary post-hoc analysis on patients who were repeat fallers (more than one fall during the course of the study, in study 306A, a phase III study of droxidopa in patients with Parkinson's disease. Overall, patients treated with droxidopa (n=24) experienced fewer falls compared to placebo (n=27), 79 total falls versus 197. The majority of falls occurred in a smaller group of patients who fell more frequently. The repeat fallers group (n=22) showed greater benefit from droxidopa therapy than the non-repeat fallers group (n=29) by a number of clinical measures, including dizziness (the difference favoring droxidopa over placebo was 2.1 units among repeat fallers, compared with 0.1 among non-repeat fallers).

Droxidopa (droxidopa), the lead investigational agent in Chelsea Therapeutics' pipeline, has been studied in two phase III clinical trials for the treatment of symptomatic neurogenic orthostatic hypotension in patients with primary autonomic failure -- a group of diseases that includes Parkinson's disease, multiple system atrophy (MSA) and pure autonomic failure (PAF). Droxidopa is a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally. The most common adverse event (greater than or equal to 5%) during placebo controlled trials was headache. Droxidopa is also being investigated for and completed phase II trials in intradialytic hypotension and adult attention deficit hyperactivity disorder and fibromyalgia.

Neurogenic OH is a chronic neurogenic disorder resulting from deficient release of norepinephrine, the neurotransmitter used by sympathetic autonomic nerves to send signals to the blood vessels and the heart to regulate blood pressure. This deficiency results in lightheadedness, dizziness, blurred vision, fatigue, poor concentration and fainting episodes when a person assumes a standing position. Symptoms of chronic Neurogenic OH can be incapacitating, not only putting patients at high risk for falls and associated injuries, but also severely affecting the ability to perform activities of daily living that require standing or walking.

Chelsea Therapeutics is a biopharmaceutical development company that acquires and develops innovative products for the treatment of a variety of human diseases, including central nervous system, rheumatoid arthritis, psoriasis and other inflammatory diseases.