Michael J. Fox powerfully describes the challenges associated with the variability of his medication in a recent NPR Interview.
Over one million people in the US and six million people worldwide suffer from Parkinson's disease, a neurodegenerative disorder caused by the diminished production of dopamine, a key neurotransmitter, resulting in progressive impairment of motor function including tremors, rigidity and difficulty in moving. The unreliability of available medications for symptomatic treatment of Parkinson’s disease remains a significant unmet need. Even when treated with the current standard of care, the majority of Parkinson’s patients continue to experience motor fluctuations where the symptoms return rapidly and unpredictably. These unpredictable OFF episodes reduce patients’ ability to lead productive, independent lives and are recognized by patients, care givers and healthcare professionals as one of the most troubling and debilitating issues associated with the disease.
L-dopa remains recognized as the most efficacious and widely used treatment for Parkinson’s disease symptoms in spite of this intrinsic unreliability. Oral L-dopa, used for chronic symptom management, is administered to maintain dopamine levels in the brain above the therapeutic threshold; however, the effectiveness of oral L-dopa formulations is significantly compromised by delayed and unpredictable absorption and excessive variability in circulating plasma drug concentrations inherent to the oral delivery route, which results in OFF episodes.
CVT-301 is being developed as an adjunct on-demand (PRN) therapy to standard oral L-dopa therapy to address OFF episodes as they emerge and enable patients to reliably manage their symptoms. By delivering L-dopa through the pulmonary route, it is anticipated that CVT-301 will rapidly and precisely increase the patients’ L-dopa plasma levels to alleviate sudden and unpredictable OFF episodes and bridge them to their next scheduled dose of oral medication. The ease of use of the simple ARCUS®
inhaler will allow patients to use CVT-301 wherever and whenever their oral Parkinson’s medications begin to fail them in between their regularly scheduled doses. The ARCUS®
platform is uniquely able to deliver the required large precise dose to the deep lung for rapid and predictable L-dopa absorption using a simple breath-actuated inhaler that has been shown to be easy for Parkinson’s patients to use.
A Phase 1 study in healthy volunteers showed that CVT-301 rapidly achieved target L-dopa plasma levels with a pharmacokinetic (PK) profile supportive of its therapeutic potential. The recently completed Phase 2a double blind placebo controlled dose finding study (CVT-301-002) recapitulated the PK profile in patients, produced rapid and durable improvement in motor function when administered to patients in the OFF state, and was generally safe and well tolerated at all doses tested. Civitas is currently conducting a Phase 2b study to evaluate the efficacy and safety of CVT-301 in treating emergent OFF episodes during one month of continued use. Data from the ongoing Phase 2b study is expected in the first half of 2014.
CVT-301 clinical studies conducted to date have been funded in part by grants from The Michael J. Fox Foundation for Parkinson’s Research.