Eltoprazine

Phase Preclinical Phase 1 Phase 2 Phase 3 Market
Eltoprazine Parkinson's PD-LID
Preclinical Phase completed
Phase 1 Phase completed
Phase 2 Phase in progress
Phase 3 Phase not started
Market Phase not started
Eltoprazine Adult ADHD
Preclinical Phase completed
Phase 1 Phase completed
Phase 2 Phase in progress
Phase 3 Phase not started
Market Phase not started
Eltoprazine Alzheimer's Aggression
Preclinical Phase completed
Phase 1 Phase in progress
Phase 2 Phase not started
Phase 3 Phase not started
Market Phase not started

Eltoprazine is a small molecule 5HT1A/1B partial agonist in clinical development for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID) and adult attention deficit hyperactivity disorder (ADHD). Eltoprazine has been evaluated in over 680 human subjects to date, and has a well-established safety profile. Eltoprazine was originally developed by Solvay Pharmaceuticals for the treatment of aggression. Upon Solvay's merger with Abbott Pharmaceuticals, the eltoprazine program was out-licensed to PsychoGenics. PsychoGenics licensed eltoprazine to Amarantus following successful proof-of-concept trials in PD-LID and adult ADHD.

Parkinson's disease is a chronic, progressive neurodegenerative disorder that causes motor symptoms such as tremors, rigidity and slowed movements as well as non-motor symptoms including cognitive impairment, mood disorders and autonomic dysfunction. The Parkinson's Disease Foundation estimates that there are approximately one million people living with Parkinson's disease in the United States and seven to 10 million PD patients worldwide. The most commonly prescribed treatments for Parkinson's disease are levodopa-based therapies. In the body, levodopa is converted to dopamine to replace the dopamine loss caused by the disease. As dopamine neurons in the brain are lost the therapeutic efficacy of levodopa attenuates, and increased use is associated with a side effect of dyskinesias. These are involuntary, uncontrollable and often exaggerated and jerky movements. They are distinct from the static, rhythmic tremor as a symptom of Parkinson's disease. Levodopa-induced dyskinesia can be severely disabling, rendering patients unable to perform routine daily tasks.

Attention deficit hyperactivity disorder (ADHD), is a psychiatric disorder of the neurodevelopmental type in which there are significant problems of attention, hyperactivity, or acting impulsively that are not appropriate for a person's age.

SUMMARY OF THE DATA WITH ELTOPRAZINE:

  • The data produced demonstrated that at both 5mg and 10 mg, the study met its Primary endpoint as measured by change from baseline in ADHD-RS-IV score in 5mg (p=0.003) and 10mg (p=0.037) doses which were statistically significantly superior to placebo with approximately 25% greater efficacy compared to placebo. Total ADHD-RS-IV scores improved by 13.6, 17.9 and 17.4 points from baseline for placebo, 5mg and 10mg of eltoprazine, respectively. Inattention, Hyperactivity, and Impulsivity ADHD-RS-IV subscales were also analyzed.
  • For the Inattention subscale, both 5mg and 10mg groups showed a statistically significant benefit over placebo (0.003 and 0.039, respectively).
  • For the Hyperactivity subscale, the 5mg dose showed a statistically significant benefit in favor of eltorprazine treatment compared to placebo (p=0.008); the 10mg dose was superior to placebo, however the difference was not statistically significant (p=0.130).
  • For the Impulsivity subscale, no significant benefit was observed for either drug dose compared to placebo.
  • Both 5mg and 10mg demonstrated significantly greater improvement over placebo for CGI-I scores (p=0.023 and 0.004, respectively).
  • The percentage of subjects who were considered improved by the investigator was 57.9% for placebo, 68.4% for 5mg, and 81.1% for 10mg. The percentage difference was significant between 10mg and placebo (0.029), but it was not between 5mg and placebo (p=0.342).

The results indicate the overall positive outcomes reported on the ADHD-RS-IV were largely driven by the Inattention and Hyperactivity subscales. This phenomenon was expected because most enrolled subjects had primary deficit in Inattention at baseline. Significant benefits of the active treatments were also observed for the following secondary efficacy variables:

Profile of Mood States (POMS):

  • The 5mg dose was statistically significantly better than placebo for POMS total score (p=0.006)
  • Both the 5mg and 10mg groups were statistically significantly better than placebo for anger-hostility score (p<0.001 and p=0.036, respectively)
  • The 5mg group was also statistically significantly better than placebo for tension anxiety score (p=0.046)

Barnes Akathisia Scale (BAS)

  • Both 5mg and 10mg groups showed a reduction in restlessness and were statistically significantly better than placebo for BAS (p=0.029 and p=0.007, respectively)
  • Both 5mg and 10mg groups were statistically significantly better than placebo for Awareness of Restlessness subscore (p=0.003 and p<0.001, respectively).
  • The 10mg group was also statistically significantly better than placebo for Distress Related Restlessness subscore (p=0.047)

Abnormal Involuntary Movement Scale (AIMS)

  • 10mg showed a significantly greater reduction in abnormal movements than placebo (p<0.001)