- A phase 3, approximately 800-person trial of a molecule called dexpramipexole (formerly KNS-760704) has launched; it will be conducted at multiple locations in 28 states and 10 other countries.
- Earlier results from a two-part phase 2 clinical trial showed that dexpramipexole is safe and well-tolerated. Additionally, the experimental treatment showed a trend toward dose-related slowing of functional decline, and a trend at the highest dose toward extending survival.
- Dexpramipexole's early development was conducted by Knopp Neurosciences (now Knopp Biosciences). In August 2010, the biotech firm Biogen Idec licensed the compound from Knopp and will lead the development of dexpramipexole for ALS.
Update 8/31/11: Enrollment screening for this study has closed to new prospective participants.
"EMPOWER," a large-scale, global phase 3 clinical trial of a molecule called dexpramipexole in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease), has begun recruiting participants. The trial will be conducted at study sites in 28 U.S. states and 10 other countries, under the auspices of the biotech firm Biogen Idec, headquartered in Weston, Mass.
The molecule, which has demonstrated favorable effects in phase 1 and 2 human clinical trials, received "orphan drug" designation from the U.S. Food and Drug Administration in October 2007, and "fast-track" designation in September 2009.
Dexpramipexole, also known as (R+) pramipexole, was developed under the name KNS-760704 by Knopp Biosciences (then called Knopp Neurosciences) of Pittsburgh.
Dexpramipexole's chemical structure is the mirror image of Mirapex, a prescription drug approved for the treatment of Parkinson disease and restless legs syndrome. The structural difference between the two molecules results in significantly different pharmacological effects.
Mirapex, also known as (S-) pramipexole, mimics the actions of a neurotransmitter called dopamine, which would be an undesirable strategy for ALS.
Although its mechanism of action in ALS remains unclear, dexpramipexole has demonstrated neuroprotective properties in multiple studies involving cell cultures and laboratory animals. It may work by improving the function and efficiency of cellular "energy factories" called mitochondria. In ALS, mitochondria endure a cell-damaging process called oxidative stress. It's suspected that dexpramipexole may help maintain energy production in stressed mitochondria within motor neurons. (See Knopp Neurosciences to Pursue Development of 'Mirror-Image' Molecule.)
About the phase 1 and 2 trials
Dexpramipexole was reported in 2007 to be safe and well-tolerated in three phase 1 studies conducted in healthy volunteers, who received the experimental treatment in single or multiple doses for up to four-and-a-half days.
Encouraging results from a two-part phase 2 trial of dexpramipexole were announced December 9, 2009, at the 20th International Symposium on ALS/MND in Berlin. Study investigators reported that the drug proved to be safe and well-tolerated. Additionally, it appeared to confer benefits — including a trend toward dose-related slowing of functional decline and another trend, at the highest dose, toward extending survival — in 102 people with ALS who took it for a total of nine months.
Biogen Idec and Knopp entered into an agreement Aug. 18, 2010, to continue development of dexpramipexole as an experimental treatment for ALS. (See Biogen Idec and Knopp Neurosciences Announce License Agreement for Late-Stage ALS Drug Candidate.)
About the new phase 3 trial
This phase 3 trial in the United States, Canada, Europe and Australia is slated to include approximately 800 people with ALS, who will be randomly assigned to one of two groups. In the treatment group, trial participants will receive 150 milligrams twice daily of dexpramipexole; those in the control group will receive a placebo. Everyone enrolled in the study will be followed for a period of 12-18 months.
Researchers will assess trial participants using the ALS Revised Functional Rating Scale (ALSFRS-R), a validated ratings scale used by physicians to monitor the progression of disability in individuals with ALS. They also will assess effects on survival and functional decline, and will characterize the molecule's pharmacokinetics (how the body handles the drug).
A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur. MDA has no ability to influence who is chosen to participate in a clinical trial. To learn more, see Understanding Clinical Trials and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to www.clinicaltrials.gov.
Trial participants are required to undergo monthly evaluations, but will be required to visit the clinic only every other month. On alternate months, functional assessments will be conducted over the phone and a nurse will visit the participant's home to draw blood for lab tests. In cases where travel to the clinic becomes too difficult, individuals can continue to participate in the trial, with all monthly assessments conducted via phone and by a home health nurse.
- be aged 18 to 80;
- have a diagnosis of sporadic or familial 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); and
- be able to swallow tablets at the time of study entry.
Special considerations exist for those taking or not taking riluzole (Rilutek), a standard ALS treatment. Those who never have taken riluzole are eligible; those who currently are taking the drug must have been on a stable dose for at least 60 days; and those who have discontinued riluzole must have stopped taking it for at least 30 days.
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; or
- currently be taking pramipexole or other dopamine agonists.
For additional details and a list of trial locations, see Phase 3 Study of Dexpramipexole in ALS (EMPOWER).
Contact the medical director for the EMPOWER study at ALSclinicaltrials@biogenidec.com; or call Biogen Idec Patient Services at (877) 312-9676 and select option 2 from within the United States. If calling from outside the United States, use +1 (919) 993-7311 and selelct option 2.
Editor's note: This story was updated 06/23/2011 to include the new Biogen Idec Patient Services phone numbers.
Editor's note: This story was updated 08/31/2011 to indicate that recruitment of new participants for the EMPOWER study formally closed on Aug. 30, 2011.