Parkinson's Disease Psychosis

Disease and Market Overview

Parkinson's disease is a chronic, progressive neurological disorder that results from the degeneration of neurons in a region of the brain that controls movement. This degeneration creates a shortage of an important brain signaling chemical, or neurotransmitter, known as dopamine, rendering patients unable to initiate their movements in a normal manner. Parkinson's disease is characterized by a number of symptoms including tremors, limb stiffness, slowness of movements, and difficulties with posture and balance. The severity of Parkinson's disease symptoms tends to worsen over time.

According to the American Parkinson's Disease Association, over 1.5 million people in the United States suffer from this disease. Parkinson's disease is more prevalent in people over 60 years of age, and the incidence and prevalence of this disease is expected to increase as the average age of the population increases. In 2004, approximately $2.5 billion was spent on drug therapy worldwide to treat Parkinson’s disease.

Parkinson's disease patients are currently treated with dopamine replacement therapies such as levodopa, commonly referred to as L-dopa, and dopamine agonists, which are molecules that mimic the action of dopamine. These therapies are relatively effective in controlling the symptoms of the disease in most patients and the use of these agents normally is required throughout the course of the disease. Studies have suggested that up to 40 percent of patients with Parkinson's disease will develop psychotic symptoms, commonly consisting of visual hallucinations and delusions. The development of psychosis in patients with Parkinson's disease often disrupts their ability to perform many of the activities of daily living that keep them independent and active. As a result, Parkinson's disease psychosis is associated with increased caregiver burden, nursing home placement, and increased mortality.

Currently, there is a large unmet medical need for new therapies that will effectively treat Parkinson's disease psychosis without impairing motor function. There is no approved therapy in the U.S. for Parkinson's disease psychosis.

Our Parkinson's Disease Psychosis Program

Pimavanserin for Treatment of Parkinson's Disease Psychosis

Pimavanserin, a proprietary small molecule discovered by ACADIA, is in Phase III development for treatment of Parkinson's disease psychosis. Pimavanserin is given orally and blocks the activity of the 5-HT_2A receptor, a drug target that plays an important role in the treatment of various neuropsychiatric disorders.

ACADIA is currently conducting two Phase III pivotal trials in its program with pimavanserin as a treatment for Parkinson’s disease psychosis. The Phase III trials are designed to evaluate the safety and efficacy of pimavanserin as a treatment for Parkinson's disease psychosis.

ACADIA is also currently conducting an open-label safety extension study under which patients who have completed either of the Phase III Parkinson’s disease psychosis trials will have the opportunity to enroll if, in the opinion of the physician, the patient may benefit from continued treatment with pimavanserin.

In March 2006, we announced results from a multi-center, double-blind, placebo-controlled Phase II study that showed that pimavanserin demonstrated motoric tolerability, antipsychotic effects, and safety in patients with Parkinson's disease psychosis. The trial enrolled 60 patients at multiple clinical sites in the United States. The study involved once-daily oral administration of either pimavanserin or placebo for a 28-day period to patients who also received their stable dopamine placement therapy.

In conjunction with the aforementioned Phase II trial, ACADIA is conducting an open-label extension study designed to determine the safety of pimavanserin during long-term administration. The study involves the extended use of pimavanserin in patients with Parkinson's disease psychosis who have completed the aforementioned Phase II trial and may, in the opinion of the treating physician, benefit from continued treatment with pimavanserin.

In a double-blind, placebo-controlled Phase Ib/IIa clinical trial completed in 2004, ACADIA assessed the safety and tolerability of pimavanserin in 12 patients with Parkinson's disease on standard dopamine replacement therapy. Pimavanserin was well tolerated in these patients. Importantly, the motor skills of these patients did not deteriorate, an effect commonly seen with other antipsychotic drugs. In addition, patients who entered this trial with treatment-induced dyskinesias exhibited indications of antidyskinetic activity after pimavanserin administration.

In 2003, we completed two Phase I clinical trials that assessed the safety, tolerability and blood drug levels of pimavanserin following oral administration in a total of 57 healthy volunteers. The results showed that pimavanserin was well tolerated at plasma levels of 229 nanograms per milliliter and below. No serious adverse events were reported at any plasma level of pimavanserin. In addition to our Phase I clinical trials with pimavanserin, we conducted drug receptor occupancy studies in healthy volunteers using positron emission tomography, or PET, with various single doses of pimavanserin. This study demonstrated that even low acute doses of this drug candidate produced significant occupancy of 5-HT_2A receptors in the human brain.

ACADIA is also developing pimavanserin as a co-therapy for schizophrenia and for the treatment of sleep maintenance insomnia. For more information on these programs, click here.

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