Solanezumab Shows Potential Disease-Modifying Effect in AD

Megan Brooks

July 22, 2015

WASHINGTON ― Study results released today show potential disease-modifying effects of the antiamyloid solanezumab (Eli Lilly and Company), with the drug showing some benefits in cognition and function when started early in the course of the disease.

"The results support the potential benefit of starting treatment with solanezumab earlier rather than later in disease progression and suggest there is persistence of treatment effect even after the delayed-start patients are given the drug," Paul Aisen, MD, director of the Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, said in a statement.

Dr Aisen presented the results of the EXPEDITION extension study here at the Alzheimer's Association International Conference (AAIC) 2015. The results were simultaneously published in Alzheimer's and Dementia: Translational Research and Clinical Investigations.

In the phase 3 companion EXPEDITION 1 and EXPEDITION 2 studies, patients with mild to moderate AD received placebo or solanezumab 400 mg infused intravenously every 4 weeks for 18 months.

Analyses from the two original trials did not show a significant benefit of solanezumab for the original coprimary end points: the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living inventory in the population with mild to moderate AD.

However, there was evidence of benefit in cognition and function in the subgroup with mild AD, which has now been confirmed in the EXPEDITION-EXT study.

In the ongoing EXPEDITION-EXT study, patients who had been receiving placebo in the first two studies were offered solanezumab; those who had been receiving solanezumab continued to take it. Patients and site personnel remain blinded to original treatment assignment, "preserving the randomized, double-blind nature of the entire 3.5-year delayed-start design," the researchers explain in a meeting abstract.

Altogether, 1322 patients with mild AD were allocated to either the delayed-start (n = 663) or the early-start (n = 659) group. Of the 1024 patients who completed the placebo-controlled period (pooled EXPEDITION 1 and EXPEDITION 2), 95.2% (n = 975) entered the delayed-start period (EXPEDITION-EXT); 58.2% of the delayed-start (n = 286) and 61.0% of the early-start patients (n = 295) completed 2 years in the delayed-start period.

This study tested whether there was a potential disease-modifying effect of solanezumab using a delayed-start analysis by applying a noninferiority test framework to see whether the delayed- start patients caught up with the early-start patients, Eli Lilly explains in a news release.

The researchers found that treatment differences at 28 weeks in EXPEDITION-EXT between the early-start and the delayed-start groups for cognition and function were similar to differences at the end of the placebo-controlled period, within a predefined margin. In other words, the delayed-start group did not "catch up."

They also found that treatment differences between the early-start and the delayed-start groups for cognition and function remained significant through 52 weeks.

"We are particularly excited about these data because this is the first time the delayed-start methodology has been implemented for an Alzheimer's disease clinical trial," study investigator Hong Liu-Seifert, PhD, from Eli Lilly, said in the company news release.

"This new analytical method enabled us to assess if solanezumab had an effect that is consistent with slowing progression of disease by modifying the underlying disease progression, which, up until now, has not been studied. These results support the trial design and delayed-start analysis plan of EXPEDITION 3, which is expected to have the last patient visit in October 2016," Dr Liu- Seifert said.

The study was funded by Eli Lilly. Dr Aisen is a research collaborator for the company.

Alzheimer's Association International Conference (AAIC) 2015. Abstract F4-03-02. Presented July 22, 2015.

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