WASHINGTON — One of the most highly anticipated new drugs to treat Alzheimer’s disease in development, Biogen’s aducanumab, failed to demonstrate a statistically significant effect in slowing progression of the disease in patients who were taking a mid-level dose of the biologic medication.
At the Alzheimer’s Association International Conference 2015, Biogen released data from a cohort of a phase 1b trial in 30 patients who were taking 6 mg/kg of aducanumab for 54 weeks. Back in March, the biotech shared data from patients taking 1 mg/kg, 3 mg/kg, and 10 mg/kg doses.
While results from Biogen’s PRIME study indicate that higher doses were associated with greater impact in helping to destroy toxic beta amyloid plaque, results for inhibiting the progression of Alzheimer’s was less clear. Based on the Mini Mental State Examination, a cognition test, the 6 mg/kg dose did not do as well as the 3 mg/kg dose. Patients taking a 6 mg/kg dose declined by an average of 1.96 points, compared to an average 0.70 point decline for the 3 mg/kg cohort.
On another measure, the Clinical Dementia Rating Sum of Boxes (CDR-SB), the 6 mg/kg dose did a little better, with a 1.11 point average decline, compared to a 1.37 point decline for the 3 mg/kg group.
Biogen has already said it is moving forward with two phase 3 trials, ENGAGE and EMERGE, which have begun enrolling patients, and will measure aducanumab’s efficacy in people with early-stage Alzheimer’s.
The big question now is what doses will Biogen test in phase 3, given that while higher doses were associated with better efficacy, it also led to more troublesome side effects. For example, the 10mg/kg dose appears to be the most effective, yet 55% of patients on this dose experienced edema in the brain. Even worse, 35% of patients who had the APOE E4 genetic variant, a known biomarker for increased Alzheimer’s risk, stopped taking aducanumab.
The company also reported that 20% of patients on the biologic had headaches, and the likelihood went up with higher doses. A Biogen spokesperson told Xconomy.com that only two doses will be examined in phase 3, but declined to say what those doses would be.
Sevigny J, et al. Oral Presentation #O4-04-05. Aducanumab (BIIB037), An Anti-Amyloid Beta Monoclonal Antibody in Patients With Prodromal or Mild Alzheimer’s Disease: Interim Results of a Randomized, Double-Blind, Placebo-Controlled, Phase IB Study. Presented at: Alzheimer’s Association International Conference 2015; July 18-23, 2015; Washington, D.C.