New data on Eli Lilly’s experimental Alzheimer’s drug, solanezumab, leave open the possibility that it and similar drugs might slow the progression of the dreaded disease if researchers can figure out how to catch patients soon enough.
But proving that will require large-scale clinical trials and it will be many years before the research will result in a medicine that will help patients who are at-risk for Alzheimer’s disease. And the potential for failure is still very very real.
Is this drug effective? “Definitely maybe,” says Sam Gandy, director of the Center for Cognitive Health at the Mount Sinai Medical Center in New York. “It’s neither a definite success, nor is it a definite failure. I think it’s enough encouragement to focus on the earliest stages of Alzheimer’s and see if something that’s really compelling can come from the next trial.”
Solanezumab is an antibody drug designed to block amyloid beta, a protein thought to be key in the process that destroys the brain in Alzheimer’s. Pfizer, Johnson & Johnson and Elan recently scrapped another beta amyloid antibody when it failed to have efficacy. The solanezumab results are better, but are still muddy.
Lilly announced in August that in one 1,040-patient clinical trial and in a second 646-patient study, there were no statistically significant benefits for giving patients solanezumab for eighteen months, compared to placebo, on either the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), a test used to measure patients symptoms, or the Activities of Daily Living Inventory, a measure of how well patients are functioning. (A statistically significant result is unlikely to be due to chance; results that are not statistically significant are looked on by researchers as mere accidents.)
Combining the two studies to increase statistical power resulted in a statistically significant reduction in how fast patients’s cognitive function worsened, measured by the ADAS-cog scale; the patients on solanezumab got a bit more than 6 points worse, while those on placebo got a little less than 8 points worse. There was still no evidence that the drug helped patients function better, though.
What really made the data look better was eliminating the sickest patients. In the 1,040-patient study, patients with milder disease had a 42% lower reduction in how fast they declined on one version of the ADAS-cog test. Sola still didn’t slow their decline on the test of how well they were functioning.
In the 646-patient study, there were no statistically significant benefits even in this milder group. But there were hints of efficacy: a 20% reduction in how fast patients declined on a different version of the ADAS-cog, and a 19% reduction on the Activities of Daily Living Inventory.
When the mild patients from both studies are pooled together, the benefit of ADAS-cog is still significant, at a 34% reduction, and the benefit on the daily living inventory comes close to being statistically significant, a 17% decrease in how much worse patients got.
This is promising because so far no drug has been able to reduce the speed at which Alzheimer’s worsens. But it will almost certainly require that Lilly conduct a second set of large, long clinical trials before seeking approval from regulators such as the Food and Drug Administration. And it’s worth noting that we’re still talking about a very small difference in how fast patients get worse – a few points on a test of cognitive ability.
“One would have hoped that if we had a treatment that arrested Alzheimer’s pathology, that we would see more than a marginal difference in this many subjects over such a long period of time,” says Marc L. Gordon, M.D., Chief of Neurology at Zucker Hillside Hospital in Glen Oaks, NY. “It suggests that in this population we may be doing too little too late.”
The promise of this study is that Lilly may be able to run a second set of trials that test the drug only in mild patients. It might be necessary to do tests at the beginning of the study to show that patients actually do have buildup of beta-amyloid in their brains; Eli Lilly has an approved drug, Amyvid, that might be used for this purpose. It’s possible that Lilly might have a shot at approval in several years. Bernstein analyst Timothy Anderson, who recommends Lilly shares, wrote in a note to investors that he models a 2016 approval for solanezumab and that today’s results are “very good” relative to what investors were expecting. It’s worth cautioning that any data that have to be massaged this much to yield a positive result should not be looked at as giving a definitive answer.
The history of Alzheimer’s research so far is made up of products that seemed to show promise, then failed. It’s not impossible that when larger studies are done, solanezumab will fade away as well.