Biogen (BIIB) Presents New Data from Long-Term Extension of Phase 1b Study

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Biogen Presents New Data from Long-Term Extension of Phase 1b Study of Investigational Alzheimer’s Disease Treatment Aducanumab

Biogen (BIIB) will present new data from the long-term extension (LTE) of its ongoing Phase 1b study of aducanumab, the company’s investigational treatment for Alzheimer’s disease, at the Clinical Trials on Alzheimer’s Disease (CTAD) meeting, Boston, November 1 – 4.

The data include results from patients in the Phase 1b study who were treated with a gradually increased dose of aducanumab for up to 24 months and those who were treated with a fixed dose of 3, 6 or 10 mg/kg aducanumab for up to 36 months. The results are consistent with previously reported analyses from the Phase 1b study and support the design of the ongoing Phase 3 studies of aducanumab for early Alzheimer’s disease.

“We now have up to three years of results from the Phase 1b study of aducanumab and during this time period we continued to observe reduction of the biomarker, amyloid plaque,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “The results also suggest there is a benefit on clinical decline for patients in the Phase 1b study, especially at the highest doses of aducanumab. Our Phase 3 studies of aducanumab are ongoing to determine whether it may be a potential treatment for early Alzheimer’s disease.”

About the Phase 1b study
The Phase 1b study is a randomized, double-blind, placebo-controlled, multiple-dose study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of aducanumab in patients with prodromal or mild Alzheimer’s disease. The study includes fixed dosing at 1, 3, 6 and 10 mg/kg as well as an arm with a titration regimen in which patients received a gradually increased dose of aducanumab until they reach a maximum dose of 10 mg/kg.

The new analyses presented at CTAD include 143 patients in these groups:

  • Patients (n=18) initially randomized to titration dosing that gradually increased aducanumab from 1 to 3 to 6 then 10 mg/kg in the 54-week placebo-controlled period and treated up to 24 months
  • Patients (n=69) randomized to aducanumab 3, 6 or 10 mg/kg in the 54-week placebo-controlled period and treated up to 36 months
  • Patients (n=48) who were randomized to placebo or aducanumab 1 mg/kg in the 54-week placebo-controlled period who were switched to aducanumab 3 mg/kg or to a 3 to 6 mg/kg titration regimen in the LTE and treated up to 24 months
  • Patients (n=8) who were randomized to placebo in the 54-week placebo-controlled period who were switched to titration dosing that gradually increased their dose from 1 to 3 to 6 then 10 mg/kg in the LTE and treated up to 12 months

In the Phase 1b LTE, the most commonly reported adverse events were headache, fall and amyloid-related imaging abnormalities (ARIA). Of the 185 patients dosed with aducanumab in the Phase 1b study, 46 patients experienced ARIA-E (edema). There were no new cases of ARIA-E in patients who continued on the same dose of aducanumab.

The incidence of ARIA-E in patients switching from placebo to aducanumab in the LTE was consistent with the incidence reported in the placebo-controlled portion of the Phase 1b study. Six patients experienced more than one episode of ARIA-E. These recurrent events were consistent with other ARIA events reported to date; they were typically asymptomatic, and most patients continued in the study.

24-Month Data
Patients who completed the 54-week, placebo-controlled period of the Phase 1b study had the option to continue in the LTE. Of the 196 patients who received placebo or aducanumab treatment in the placebo-controlled period of the Phase 1b study, 143 continued into the LTE. All patients who continued in the LTE were switched to or continued on aducanumab treatment.

Amyloid plaque levels were measured by positron emission tomography (PET) using the standardized uptake value ratio1 (SUVR) and continued to decline in those who remained on treatment for 24 months.

The Clinical Dementia Rating sum of boxes (CDR-SB) and the Mini-Mental State Examination (MMSE), which measure aspects of cognitive and physical function that can be affected by Alzheimer’s disease, were exploratory endpoints of the Phase 1b study. The results of these assessments suggest a continued benefit on the rate of clinical decline during the second year of treatment with aducanumab.

By 24 months, patients treated in the titration treatment group had an expected average dose of 7.6 mg/kg.

At 24 months, the mean change from amyloid plaque levels at the start of the Phase 1b study was:

  • -0.170 in those who switched from placebo to aducanumab treatment at 12 months
  • -0.149 in those who switched from 1 to 3 mg/kg at 12 months
  • -0.197 in the 3 mg/kg treatment group
  • -0.280 in the 6 mg/kg treatment group
  • -0.322 in the 10 mg/kg treatment group
  • -0.271 in the titration treatment group

At 24 months, the average decline from the start of the Phase 1b study on the CDR-SB was:

  • 3.25 points in those who switched from placebo to aducanumab treatment at 12 months
  • 3.52 points in those who switched from 1 to 3 mg/kg at 12 months
  • 2.32 points in the 3 mg/kg treatment group
  • 2.98 points in the 6 mg/kg treatment group
  • 1.69 points in the 10 mg/kg treatment group
  • 2.65 in the titration treatment group

At 24 months, the average decline from the start of the Phase 1b study on the MMSE was:

  • 4.28 points in those who switched from placebo to aducanumab treatment at 12 months
  • 3.65 points in those who switched from 1 to 3 mg/kg at 12 months
  • 2.81 points in the 3 mg/kg treatment group
  • 5.20 points in the 6 mg/kg treatment group
  • 1.97 points in the 10 mg/kg treatment group
  • 1.95 in the titration treatment group

36-Month Data
In patients treated up to 36 months, amyloid plaque as measured by PET using SUVR, continued to decrease in a dose- and time-dependent manner, with amyloid plaque levels in the 10 mg/kg fixed-dose treatment group reaching and remaining at a level considered below the quantitative cut-point that discriminates between a positive and negative scan.2

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