Sometimes the medicine can be as difficult to swallow as the illness. Such is the case for many of the 15 million patients suffering depression in the U.S., who today have a variety of FDA-approved medications to choose from, but finding the right one at the right dose can be intolerable, to the point of abandoning therapy.
Data from a study sponsored by Aspect Medical Systems (Newton, Massachusetts) could help guide physicians in choosing the best drug at the optimum dosage. Using its EEG-based Antidepressant Treatment Response (ATR) indicator, Aspect reported study results from the Biomarkers for Rapid Identification of Treatment Effectiveness (BRITE) trial in major depression during a Tuesday conference call to investors and the media.
The trial, which was completed by 282 patients who sat for several EEG tests over the course of 90 days, sought to:
• Validate Aspect’s ATR indicator as a biomarker of clinical response to selective serotonin reuptake inhibitors (SSRI).
• Determine the best treatment option for patients who are predicted to be non-responders to a SSRI.
• Assess whether the technology can identify worsening of adverse events, e.g. suicidal ideation.
• Expand EEG database to allow further refinements of Aspect’s algorithms and product offering.
“In the final analysis, 52% of subjects in the escitalopram arm and 47% across all study arms met the definition for response in week seven,” said Andrew Leuchter, MD, professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at the University of California Los Angeles.
All patients were initially started on escitalopram (Lexapro). One group continued on that drug, and the dosage was increased if Hamilton Depression Rating Scale (HAM-D) scores were greater than seven. A second arm was switched to bupropion XL (Wellbutrin) and the dosage was increased if the HAM-D score was greater than seven. A third group received a combination of both drugs and the clinician had the choice to increase dosages depending on HAM-D scores.
Throughout the 90-day trial, patients had seven EEG tests across the SSRI challenge, initial response and dose escalation phases.
“Subjects were considered responders to treatment if they experienced a 50% reduction or significant improvement in HAM-D scores and they were considered remitters if they achieved a HAM-D score less than or equal to seven at the seven-week primary endpoint,” said Leuchter. “This means they recovered from their depressive episodes.”
The study found that ATR is a significant predictor of response and remission after one week of treatment in depressed subjects receiving seven weeks of escitalopram. It also found that ATR-predicted non-responders to escitalopram experienced significantly higher response rates if switched to bupropion after one week of escitalopram, suggesting that a one-week biomarker of treatment response could have important clinical benefits.
Nassib Chamoun, Aspect Medical’s president/CEO, said, “These results give us the confidence to move forward to the next pivotal trial, which we are currently designing with feedback from the FDA and our advisors. We plan to initiate the trial in the second quarter of 2008. This will be half the size of BRITE and will focus on prediction accuracy as the primary endpoint. If this next trial is successful, it will lead to a filing seeking FDA clearance in 2009.”
Assuming positive outcomes, Aspect said it plans to launch the product to a group of about 8,000 psychiatrists in a Phase I launch that would last 18 to 24 months to get a market foothold while gaining evidence for reimbursement.
As market opportunities grow, Aspect plans to seek a commercialization partner, Chamoun said.
“We believe the development of our technology is well timed to take maximum advantage of the trend toward personalized medicine and has the potential to be extremely attractive to patients, clinicians and payers alike, particularly in psychiatry where the trial and error approach still predominates,” he said.
Chamoun added that the need for biomarkers is even more acute when more costly and invasive approaches to treatment are used, such as neurostimulation. He said that for that reason, Aspect is allocating additional resources to the development of biomarkers for use in neurostimulation.
The study is an effort to build on Aspect’s BIS Monitoring System for central nervous system uses other than its initial purpose: to monitor brain activity during surgery or sedation. In that technology, sensors are placed on the patient’s forehead to measure electrical activity in the brain via EEG and translate it into a number between 100 (wide awake) and zero (absence of brain electrical activity).
In addition to aiding physicians in medication choices, the ATR system can predict remission. “We were very pleased to see ATR also emerging as a predictor of remission, which is extremely important from a clinical standpoint because the goal of treatment is to achieve remission,” said Leuchter. “Remission is a much less frequent occurrence than response in antidepressant treatment and can take a very long time to achieve. So to be able to predict this outcome would be particularly valuable to physicians.
“Practically speaking, ATR could potentially provide the greatest clinical benefit for those patients who might be kept on a medication that is unlikely to help them,” he added.