Biogen Inc.’s experimental drug for Alzheimer’s disease failed to show a statistically significant cognitive benefit for patients on a closely watched dose, complicating the company’s quest to develop a treatment.
The findings, in data released Wednesday, leave unresolved questions about the appropriate dosage for the drug, even as Biogen moves into the next phase of trials. Investors have pinned their hopes on the treatment, driving shares up 33 percent since initial data was announced in December.
Earlier data had already demonstrated that the drug showed a better response at higher doses, though it also showed harsher side effects. The new results didn’t provide clear direction on whether a dose somewhere in the middle would be the answer.
Biogen shares dropped 3.9 percent to $393.35 at 9:37 a.m. in New York. The stock had gained 35 percent in the last year, as of Tuesday’s close.
At a dose of 6 milligrams per kilogram, patients on Biogen’s drug BIIB037 had a cognitive decline of 1.96 points on the Mini Mental State Examination scale, compared with 2.81 for people on a placebo -- suggesting cognitive decline was slower on the drug, though not enough to be statistically significant. And patients on a lower dose of 3 milligrams actually declined even less, with a change of 0.7 point.
On a different measure of cognitive function, called the Clinical Dementia Rating sum of boxes, patients deteriorated less on the 6 milligram dose than on the 3 milligram dose and those on a placebo. But those results also weren’t statistically significant.
Like other doses, the 6 milligram amount showed signs of reducing beta amyloid -- protein fragments linked to the memory-erasing disease.
The results were from an early-stage trial of 166 patients. The most recent data examined 30 of those patients.
The lack of significant cognitive effects in the patient group may stem from the small number of patients in the study, according to Alfred Sandrock, Biogen’s chief medical officer.
“With those small numbers it’s amazing that we have a statistically significant effect at all” in other doses, Sandrock said by phone. “I think this is pretty good and in fact it does nothing to slow us down.”
Biogen is pushing rapidly ahead into an area where other drugmakers have tried and fell short in final-stage trials. The medications solanezumab, from Eli Lilly & Co., and bapineuzumab, developed by Pfizer Inc., Johnson & Johnson and Elan Corp., both failed to show a significant effect on the disease in trials. Lilly is currently retesting solanezumab in earlier-stage patients, while bapineuzumab has been scrapped.
Some patients had brain swelling known as amyloid-related imaging abnormalities, or ARIA, that can cause headaches. Among patients carrying the ApoE4 gene, which is strongly linked with Alzheimer’s, 55 percent of patients taking the trial’s highest dose of 10 milligrams reported ARIA, compared with 43 percent in those who took 6 milligrams and 5 percent in the 1 and 3 milligram dose groups.
Biogen’s initial data in March was heralded as a significant advance in the field of Alzheimer’s, where no compound has successfully proven it can slow the course of the disease. It tests the hypothesis that amyloid beta is the target that Alzheimer’s drugs should be going after.
The trial may have avoided pitfalls that tripped up other drugmakers because it focused on patients in the early stage of Alzheimer’s disease, made sure they had beta amyloid in the brain and verified they had Alzheimer’s and not a different form of cognitive impairment.