New data from an early-stage study of Biogen’s Alzheimer’s drug aducanumab has demonstrated a clear impact on deposits of amyloid beta, the toxic tangles in the brain suspected of triggering the memory-wasting ailment. And while they couldn’t precisely prove it, the researchers spotlighted additional evidence that the drug might also be slowing the steady cognitive decline of the people taking the drug.
The evidence — a detailed retread of results that have already been reviewed — immediately triggered the kind of relentless hype that has surrounded aducanumab from the first early signs of its ability to have an impact on the disease. But there are some important caveats that enthusiasts nevertheless need to keep in mind.
First, while amyloid beta deposits are a well defined target, it’s also not universally accepted as the sole cause of Alzheimer’s. There are some who believe it may not be involved at all, pointing to patients who have the clusters in their brains but no symptoms of dementia. In addition, the researchers carefully noted that the study with 165 patients was not powered to provide clear evidence of efficacy.
The enthusiasm among the execs and researchers involved, though, was palpable. And Biogen, which badly needs to whip up some excitement for the company’s pipeline, was not in the least bit reluctant to pump the latest data set that has now been published in Nature. Chief Medical Officer Al Sandrock remarked:
“These early studies of aducanumab show its effectiveness in removing amyloid plaque from the brain as well as its potential effect on the slowing of cognitive decline in patients suffering from Alzheimer’s disease. Publication in Nature is an achievement we share with the many scientists and clinical investigators who conducted this research as well as the patients who volunteered to participate in our clinical trial; we are grateful to all of them.”
There is, however, a long way to go from a successful Phase Ib study to a pivotal win, which is where Biogen is now focused.
Shares of Biogen remained down slightly for the day.
In addition to the positive signs that the high dose was most effective, there were also some concerns.
Checking on safety, 38% of the patients in the high, 10 mg kg arm of the study dropped out, many citing side effects, compared to 25% of the placebo arm.
Biogen’s progress on Alzheimer’s has helped whip up fresh enthusiasm for the amyloid beta hypothesis, even spurring Roche to keep one of its failed drugs, gantenerumab, in the pipeline. Several late-stage drugs, including solanezumab at Eli Lilly, also attack a-beta, looking to prove their effectiveness in very early-stage patients, before the disease causes serious brain damage. New imaging techniques are also better able to identify patients who are most likely to benefit.
Lilly is expected to deliver pivotal data from its second Phase III program later in the year. But it’s also been backing away from a key endpoint on daily function, signaling that it expects to be able to prove an impact on cognition.
Biogen, meanwhile, is seeing off CEO George Scangos at a time the biotech company has been under heavy pressure to do something now to prove it has important new drugs in the pipeline that can make up for flagging sales of its flagship drug, Tecfidera. Still some ways from their pivotal read out, and unable so far to come up with the kind of deal that can generate some cheers from Wall Street analysts, Biogen will settle for trumpeting another early snapshot for aducanumab.
Jefferies’ Brian Abrahams noted:
Much of the clinical details, sub-analyses and preclinical data have all been extensively presented, and we didn’t detect anything materially new in the article; it did cite caution in interpreting cognitive endpoints given lack of powering for these measures and no imputation for missing values, and pointed out the possibility the need for MRIs in patients developing ARIA could have unblinded the study. Still, the dose-dependent plaque reductions and correlation between plaque clearance and cognitive benefits continue to look most compelling to us, and we continue to see a 45% probability of ultimately generating $2B+ revenues to BIIB by 2025.
The best place to read Endpoints News? In your inbox.
Comprehensive daily news report for those who discover, develop, and market drugs. Join 24,000+ biopharma pros who read Endpoints News by email every day.Free Subscription