Amarantus BioScience Holdings, Inc. (AMBS-OTC) provided investors with an important update today regarding the company's plans to initiate a Phase 2b clinical study of Eltoprazine in Parkinson's Disease Levodopa-Induced Dyskinesia, or PD-LID.
"We have spent the last six months evaluating the historical Eltoprazine data and laying out the clinical program going forward," said Dr. Charlotte Keywood, Chief Medical Officer of Amarantus' therapeutics division. "We have designed a robust Phase 2b study based upon a thorough evaluation of state of the art trial designs for drugs in the PD LID indication. We will be engaging with the FDA in the coming weeks to commence the regulatory process for the initiation of the PD LID clinical program in the US."
In Wednesday's press release, Amarantus listed the following required steps for moving Eltoprazine into a Phase 2b trial in the U.S. by late 2014/early 2015:
1. Request pre-IND meeting with the FDA
2. Submit IND to the FDA
3. Obtain IND approval
4. Start enrollment for the Phase 2b PD LID clinical trial in the U.S.
5. Submit Phase 2b design to EMEA (European Medicines Agency)
6. Obtain agreement on Phase 2b trial design with EMEA
7. Start enrollment for the Phase 2b PD LID clinical trial in Europe
For a discussion of the progress that Amarantus has already accomplished with Eltoprazine since in-licensing the candidate earlier this year, please refer to our Executive Informational Overview (EIO) published on the company on September 8, 2014. Details include existing data supporting the use of the compound in PD-LID as well as Adult ADHD and other indications, as well as its manufacturing qualifications, intellectual property acquisition, and Phase 2b trial design, potential target markets, and so on.
Excerpts from the EIO
What is Eltoprazine?
Eltoprazine is being developed to treat the primary side effects from Parkinson’s Levodopa-Induced Dyskinesia (PD-LID), a condition linked to PD medication levodopa, as well as Adult ADHD. A small molecule drug candidate, Eltoprazine is a selective partial agonist on the 5-HT1a/1b receptors of the serotonergic system in the brain (with the serotonergic system linked to a wide range of motor and behavioral disorders, including aggression, cognition, attention, and control). Over 700 patients to date have been given Eltoprazine at varying doses as high as 30mg, with the active dose in both PD-LID and Adult ADHD being 5mg. Primary and secondary endpoints have been met in past Phase 2 trials for both PD-LID and Adult ADHD, with the drug being well tolerated during the study and no serious adverse events reported.
What is the PD-LID that Eltoprazine seeks to treat?
Parkinson's disease (PD) treatment was revolutionized in the 1960s by the introduction of a medicine called levodopa. Following its discovery, however, patients undergoing continuous treatment with levodopa reported side effects now known as "choreoathetoid movements" and "off episodes." Today these complications of levodopa treatment are termed Levodopa-Induced Dyskinesia (LID), which is characterized by a variety of hyperkinetic and abnormal involuntary movements, involuntary muscle contractions, and other types of tics and uncontrolled movements. LID typically begins in the lower extremity ipsilateral (occurring on the same side of the body) to the side first affected by PD. In the beginning, patients may not notice subtle hyperkinetic movements; though, as it progresses, LID may interfere with activities, leading to functional impairment, disability, and poor quality of life. The risk for developing LID has been linked to the disease’s severity, younger age of onset, female sex, duration of levodopa treatment, and total levodopa exposure. A literature survey of more than 2,000 publications identified LID in roughly 40% of PD patients treated with levodopa for four to six years. An alternative review found a prevalence of LID in up to 85% of patients with PD (noting that different methods to recognize LID have resulted in disparities in its frequency rate [as reported in literature]).
Are there additional indications that Eltoprazine may be able to treat? Yes, Adult ADHD.
ADHD is a psychiatric disorder of the neurodevelopmental type (impairments of the growth and development of the brain or central nervous system), where there are significant problems of attention, hyperactivity, or acting impulsively that are not appropriate based on a person’s age. Symptoms of ADHD include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity (over-activity). As one of the most common childhood disorders, ADHD can continue through adolescence and adulthood with roughly 7.8% of all U.S. school-age children, or about 4.4 million children aged 4 to 17 years, diagnosed at some point in their lives (Source: U.S. Centers for Disease Control and Prevention [CDC]). In addition, over eight million U.S. adults have exhibited symptoms of ADHD, with only about 600,000 receiving treatment. Adult ADHD is marked by difficulty maintaining attention, as well as hyperactivity and impulsive behavior, which can lead to a number of problems, including unstable relationships, poor work or school performance, and low self-esteem.
Amarantus plans to initiate a Phase 2b clinical development program for Eltoprazine in Adult ADHD after the PD-LID program is underway.