AVP-923 for Agitation in Patients with Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia and is a progressive neurodegenerative disease eventually leading to death.  An estimated 5.4 million Americans have AD, this number has doubled since 1980, and is expected to be as high as 16 million by 2050.

AD is generally characterized by cognitive decline, impaired performance of daily activities, and behavioral disturbances.  Behavioral and psychiatric symptoms develop in as many as 60% of community-dwelling people with dementia and in more than 80% of patients living in nursing homes; the lifetime risk of such complications approaches 100%.

Frequent and severe dementia-related behavioral symptoms can be extremely distressing to the individual, the family, and caregivers. Agitation is defined as a state of poorly organized and purposeless psychomotor activity characterized by at least one of the following types of behaviors:

  • Aggressive verbal (e.g., screaming, cussing)
  • Aggressive physical (e.g., destroying objects, grabbing, fighting)
  • Non-aggressive physical (e.g., pacing)

These behavioral disturbances have been associated with more rapid cognitive decline, institutionalization, and increased caregiver burden.  Reduction or elimination of such disruptive agitated behaviors could therefore improve the ability of caregivers to manage patients at home, and perhaps postpone the need for institutionalization. With no currently approved drugs for treatment of agitation in Alzheimer’s disease, there remains a great unmet medical need for these patients.

Clinical Studies

In June 2012, Avanir initiated a Phase II clinical trial to investigate the efficacy, safety and tolerability of AVP-923 for the treatment of symptoms of agitation in patients with Alzheimer’s disease. Details on the clinical trials can be found on the NIH website or Avanir’s clinical study site.

AVP-923

AVP-923 is an investigational drug consisting of a combination of two well-characterized compounds: the active ingredient dextromethorphan hydrobromide (DM), an uncompetitive NMDA receptor antagonist and sigma-1 agonist and the enzyme inhibitor quinidine sulfate (Q), a CYP450 2D6 inhibitor, which serves to increase the bioavailability of dextromethorphan. Over 1,635 patients were exposed to AVP-923 in doses up to 60 mg of DM with 60 mg Q in 19 clinical trials in various diseases as well as healthy volunteers. Across this safety database, the most common adverse events reported were dizziness, headache and nausea which tended to improve within a few weeks of continued dosing in most patients. AVP-923 DM 20mg/Q 10 mg capsules was approved for treatment of pseudobulbar affect (PBA) in October 2010 under the trade name NUEDEXTA ® (dextromethorphan hydrobromide and quinidine sulfate).  NUEDEXTA is not approved for the treatment of agitation in Alzheimer’s patients.