In early April, Knopp Biosciences and Biogen Idec announced the enrollment of the first patient into a Phase III clinical trial of the experimental drug dexpramipexole, a novel treatment to extend the lives of individuals with ALS. It is an exciting development for the field, and we wanted to highlight some of the details and history of the drug for the blog.
The trial will enroll 804 patients who will be followed for 12-18 months. Half of this group will receive two doses per day of a 150mg oral tablet of the drug; the other half will receive a similarly dosed placebo.
In order to participate in the trial, patients must:
- Be 18 to 80 years old.
- Have a diagnosis of familial or sporadic ALS.
- Have experienced symptom onset within 24 months prior to beginning the trial.
- Meet World Federation of Neurology El Escorial criteria for a “possible,” “laboratory-supported probable,” “probable” or “definite” ALS diagnosis.
- Have lung function of 65 percent or more at screening, measured by a test called the upright slow vital capacity (SVC).
- Be able to swallow tablets at the time of study entry.
Participants must not:
- Have any other medically significant illness.
- Have any clinically significant abnormal laboratory values.
- Be pregnant or breastfeeding.
- Have prior exposure to dexpramipexole.
- Be currently taking pramipexole or other dopamine agonists.
The trial will be enrolling patients at 83 locations in 28 states and 10 countries (Australia, Canada, and several European countries). For more detailed enrollment information as well a list of study locations, visit the listing for the Phase III dexpramipexole trial at ClinicalTrials.gov. It should be noted that most sites have yet to start recruiting as of the publication of this post. Contact information for individual sites can be found at ClinicalTrials.gov, and the Medical Director of the study at Biogen can be reached at ALSclinicaltrials@biogenidec.com.
A brief history of dexpramipexole:
Early 2000’s – Dexpramipexole is first identified as a potential ALS therapy by Dr. James Bennett of the University of Virginia and first preliminary academic clinical studies are conducted using Dex to treat ALS patients.
2007 – Knopp Biosciences completes a formal Phase I trial of dexpramipexole that demonstrates the drug is safe and well-tolerated among healthy volunteers.
2009 – Results from a Phase II study of the drug again demonstrate safety and show a ‘dose-dependent trend in slowing the rate of disease progression’ in the first part of the study and a ‘trend toward a survival benefit’ among the highest-dosed patients in the second part of the study. Drug receives ‘fast-track’ designation from the US FDA.
2010 – Knopp Biosciences and Biogen Idec enter into an exclusive, worldwide license agreement to develop and commercialize dexpramipexole.
2011 – Knopp Biosciences and Biogen Idec enroll first patient in Phase III clinical trial of dexpramipexole.
So what is the expected benefit of dexpramipexole (colloquially known as dex)?
According to Michael Bozik, a neurologist and the President and CEO of Knopp Biosciences, “If we confirm in larger studies what we saw in earlier studies, we believe it has the promise to extend life [up to six months or more].”
Riluzole, the only currently available drug for ALS, extends life by about 2-3 months. Patients who are currently taking Riluzole are not disqualified from participating in the Phase III trial, though they must either have been taking a stable dose of the drug for at least 60 days or have discontinued the drug for at least 30 days.
Though the launch of this trial is an encouraging development, there are still several hurdles that must be cleared. The Phase III trial will enroll eight times the number of patients as previous Dex trials and will need to exceed the relatively ‘modest’ effect demonstrated in the Phase II trial. Additionally, the mechanism behind the drug is not well understood. According to Dr. Bozik, Knopp is still researching the underlying function of the drug in collaboration with Yale University. Finally, even if the trial demonstrates efficacy, the earliest an application for FDA approval could be submitted is 2013—assuming the study is completed on time (estimated end date of February 2013) and the FDA does not require a second round of Phase III trials.
Nevertheless, dexpramipexole provides cause for hope for the thousands of patients and families battling this disease. We will continue to closely follow and report on any developments related to this drug.