PRIME Trial Bumped to Phase 3 Following Positive Results

Amyloid plaque
Amyloid plaque
The phase 1b trial is being bumped to phase 3 after producing statistically significant reductions in amyloid plaque.

In what could be a significant event in the future of Alzheimer’s treatment, interim results from the PRIME study indicate that aducanumab reduces amyloid plaque in the brain and slows cognitive decline in people with prodromal or mild Alzheimer’s disease.

The results, which were presented at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in Nice, France, represent a snapshot of the progress being made in the ongoing Phase 1b randomized, double-blind, placebo-controlled, multiple-dose study that’s evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of aducanumab (BIIB037), which is being developed by Biogen Idec.

Following the statistically significant results, the clinical program is being moved to Phase 3 and will likely begin enrolling subjects within the year.

The interim results, which reflected data from 166 patients up to week 54 in the placebo (n=40), 1 mg/kg (n=31), 3 mg/kg (n=33) and 10 mg/kg (n=32) dose arms, and up to week 30 data for the 6 mg/kg (n=30) dose arm, showed a dose- and time-dependent reduction in amyloid plaque as well as a statistically significant slowing of clinical decline based on observations on the Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scales.

PET imaging was used to measure plaque levels at baseline, 26 weeks, and 54 weeks in the frontal, parietal, lateral temporal, sensorimotor, antierior and posterior cingulated regions of the brain. In placebo group, the standardized uptake value ratio (SUVR) was virtually unchanged at 26 and 54 weeks. Those treated with aducanumab saw a statistically significant reduction in amyloid plaque (3 mg/kg [average change of -0.087, p<0.01], 6 mg/kg [-0.143 (p<0.001)] and 10 mg/kg [-0.205 (p<0.001]) compared to placebo at 26 weeks. At 54 weeks, the 3 mg/kg and 10 mg/kg groups saw statistically significant reductions of amyloid plaque (3 mg/kg [-0.139 (p<0.001)] and 10 mg/kg [-0.266 (p<0.001)]. The 6 mg/kg group is ongoing.

MMSE scores for those in the placebo group worsened by an average of 3.14 at one year, compared to a decline of 2.21 in the 1 mg/kg group, 0.75 in the 3 mg/kg group, and 0.58 in the 10 mg/kg group. Slowing in the 3 mg/kg and 10 mg/kg groups was statistically significant compared to placebo (P-values <0.05).

CDR scores in the placebo group worsened by an average of 2.04 at one year, compared to a decline of 1.70 in the 1 mg/kg group, 1.33 in the 3 mg/kg group, and 0.59 in the 10 mg/kg group, which was statistically significant with a P-value of <0.05.

Overall, aducanumab showed an acceptable safety and tolerability profile, with the most frequent serious adverse event and adverse event being amyloid-related imaging abnormalities (ARIA). The incidence of ARIA-edema was dose- and APoE4 dependent, with 5% in the 1 mg/kg and 3 mg/kg arms, 43% in the 6 mg/kg arm, and 55% in the 10 mg/kg arm for APoE4 carriers. In ApoE4 non-carriers, the incidence of ARIA-E was 9%, 11% and 17% in the 3 mg/kg, 6 mg/kg and 10 mg/kg aducanumab groups. No cases were reported in the 1 mg/kg groups. Most patients with ARIA-E continued treatments at a lower dose. Besides ARIA, headache, which appeared to be dose-dependent, occurred in 22% of patients receiving aducanumab compared to 5% of the placebo group.