First patient enters phase III trial of Biogen's Alzheimer's drug

Biogen has enrolled the first patient in a phase III programme for aducanumab, its Alzheimer's disease candidate, despite a recent setback in an earlier trial.

The company is carrying out two late-stage trials of aducanumab, ENGAGE and EMERGE, which are designed to test the ability of the amyloid-targeting drug to slow the cognitive impairment seen in Alzheimer's patients.

During the summer, Biogen reported phase Ib data at the Alzheimer's Association International Conference (AAIC), which showed the drug was only able to show a modest effect in slowing cognitive decline in patients with mild or prodromal Alzheimer's.

The disappointment, which follows a series of failed trials for amyloid-busting drugs in Alzheimer's, lent support to those who argue that the formation of amyloid beta plaques in patients is a marker but not a driver for the neurodegeneration seen in the disease.

The results seem to have polarised opinion, with some claiming the drug is the first to show a real (and dose-responsive) impact on the disease, while others are more sceptical.

Biogen's study did show some effect of the drug at higher doses, and the promise of a drug treatment that could at last impact on the underlying mechanism in Alzheimer's – which Cowen analyst Eric Schmidt has put at a $20 billion potential market – has prompted the company to press on with its pivotal trials programme.

"Millions of people worldwide are living with Alzheimer's disease and no disease-modifying treatment options," said Biogen chief executive George Scangos in a recent investors' call.

"We believe that this important investment has the potential to be a significant future growth driver for Biogen," he added.

A key element of both ENGAGE and EMERGE will be toxicity assessment, as the phase Ib trial did reveal some safety signals, known as amyloid-related imaging abnormalities (ARIAs), including a leakage of fluid from the blood in the brain. However, analysts have suggested that the massive unmet need means that side effects will be acceptable with careful patient monitoring.

"We have accelerated our aducanumab clinical programme so that we can more fully characterise and confirm the benefit-risk profile of this investigational treatment for Alzheimer's disease," commented Biogen's chief medical officer Alfred Sandrock.

"Understanding the urgency to find effective treatments for this devastating disease, we are excited that we have enrolled our first patient in the phase III programme," he added.

ENGAGE and EMERGE are expected to include 1,350 subjects with early Alzheimer's disease, who will be screened by PET amyloid imaging to confirm elevated beta amyloid plaque levels in the brain. Study dosing will include an up-titration period in an effort to reduce ARIAs and maximise aducanumab's benefit/risk profile, according to Biogen.

Biogen is also working with Eisai on two other potential disease-modifying therapies for Alzheimer's, BAN2401 and E2609, which are in phase II trials with first data due next year. BAN2401 is an anti-beta amyloid antibody, while E2609 is an oral BACE inhibitor that seeks to block the production of amyloid plaques.

Meanwhile, the enrolment of the first patient into the trial is also a big event for Neurimmune, which stands to receive a $60 million milestone payment from Biogen under the terms of its licensing agreement for aducanumab.