Complicated News from a New Clinical Trial
The goal of Alzheimer’s research is to find a treatment that slows, stops or reverses the progression of the disease. Last Friday, Biogen Idec – as of this morning now Biogen – reported the results of preliminary studies that suggest that such a treatment may be in the works, although it will have to clear some significant hurdles.
The drug, called aducanumab, has just finished its Phase 1 clinical trial, the phase which tests the drug’s safety and appropriate dosage. There were 166 subjects in this trial who had been diagnosed with mild Alzheimer’s disease or who had amyloid plaque build up without symptoms. The subjects were divided into roughly 5 groups. One group received a placebo. The other four groups received doses of 1 mg, 3 mg, 6 mg or 10 mg, respectively, for a period of 54 weeks. (Those taking the 6 mg dosage have not yet completed the 54 week course, and their data are still be collected.)
All subjects underwent PET scans to map amyloid build up at the start of the study, and they were repeated mid-way and again at the completion of the study. The subjects also took a battery of tests that measured cognition and functionality at base line and at the study’s completion.
The Good News
Researchers are encouraged by the fact that the PET scans showed that those who received the drug had statistically significant reductions in the amount of amyloid in their brains. Further, their cognitive and functional decline was less than those who received the placebo. These improvements were linked to the dosage that they received: those who received the highest doses of the drug had the most amyloid reduction and experienced the least cognitive decline. The fact that the responses were dose-related strongly suggests that these changes are directly related to the drug itself.
The Bad News
Side Effects. The drug has some troubling side effects, most notably swelling of the brain. This adverse effect seems also to be dose related. It is known that people with a specific genetic variation, APoE4, are at a higher risk of developing Alzheimer’s than those without this variation. Those with APoE4 were far more likely to experience the brain swelling than other subjects; over half the subjects with APoE4 who took the highest dosage experienced brain swelling.
Functionality. Although the subjects receiving the drug performed better than the placebo subjects on the functionality tests, the differences in function were only statistically significant for those who received the highest doses of the drug. Other drugs that have shown promise have ultimately failed due to the inability to produce meaningful functional improvement. So the low impact on functionality may be an issue.
Small Sample Size. This study is a very preliminary one. Only 166 people were tested. Therefore, if only a few of the subjects had tested differently, the data may not have been so promising. Many other drugs have shown promise at this stage as well, only to fail larger trials.
Biogen has announced its intention of moving this drug forward to a Phase 3 trial, which will involve up to 1,000 people in different research centers. There should be more information forthcoming about where these trials will be held and how people can volunteer to participate.
During this trial, much more will be discovered about the optimum dosage, the extent and severity of adverse side effects, and the drug’s efficacy. So while this news offers encouragement, we are far from having a proven treatment for Alzheimer’s. Industry observers opine that if this drug successfully completes its Phase 3 trial, the drug will not be available until 2020.