Biogen Props Up Aduhelm's Controversial Win with New Data at Alzheimer's Conference

Biogen_Dina Rudick/The Boston Globe

Dina Rudick/The Boston Globe via Getty Images

One of the eagerly anticipated presentations at the Alzheimer’s Association International Conference being held this week in Denver, Colo., and virtually is Biogen and its partner Eisai on their controversial drug ADUHELM™ (aducanumab). Biogen is also presenting new data on a different Alzheimer’s drug with another partner, Ionis Pharmaceuticals.

Biogen and Eisai presented four posters about ADUHELM, which received accelerated approval by the U.S. Food and Drug Administration (FDA) on June 7. One of the posters presented item-level data from the EMERGE Phase III trial, meaning that it was looking at data on individual domains that made up the trial’s pre-specified endpoints of cognition, function, and behavior. The data demonstrated consistency of high-dose aducanumab treatment effects across all six domains, three cognitive and three functions, as measured by Clinical Dementia Rating-Sum of Boxes, which was the primary endpoint of the study.

The drug was also associated with a decrease in the behavioral and psychiatric symptoms of Alzheimer’s as measured by the Neuropsychiatric Inventory-10 (NPI-10), which was a tertiary efficacy endpoint of the EMERGE study.

Another poster presentation looked at the decrease in amyloid beta plaques and downstream biomarkers of Alzheimer’s in the aducanumab cohorts in the PRIME, EMERGE and ENGAGE clinical trials. A second set of analyses looked at the relationship between treatment effects on brain AB plaque levels, and the third demonstrated a smaller magnitude of clinical decline in the PRIME, EMERGE and ENGAGE studies whose brain AB plaque levels dropped to a threshold considered to be “amyloid negative relative to patients who did not reach this threshold.”

Two additional posters described subgroup analyses of the amyloid PET substudies from EMERGE and ENGAGE and considerations of real-world management of amyloid-related imaging abnormalities from EMERGE and ENGAGE in patients on the high-dose (10 mg/kg) of aducanumab.

“Our presentations to the dementia research community at AAIC of this robust set of clinical trial data will allow us to engage directly with scientists and neurologists on in-depth analyses of our findings,” said Alfred Sandrock Jr., head of Research and Development at Biogen.

Biogen and Ionis Pharmaceuticals announced topline results from a Phase Ib clinical trial of BIIB080/MAPTRX. The drug is an investigational antisense therapy that targets microtubule-associated protein tau mRNA and prevents production of tau protein.

There are two primary abnormal proteins associated with Alzheimer’s disease. One is beta-amyloid, which typically occurs early in the disease, and which is the target of aducanumab. The second is tau, which often appears later in the disease.

The Phase Ib study of BIIB080/MAPTRX hit the primary objective of safety and tolerability in mild Alzheimer’s. It also showed robust time and dose-dependent decreases of tau protein in cerebrospinal fluid (CSF) in these patients over the three-month treatment period as well as sustained reductions in the six-month post-treatment period.

Patients receiving the drug demonstrated dose-dependent decreases in total-tau concentration in CSF eight weeks after the last dose with a mean percentage reduction of 30%, 40% and 49% in the low, medium and high dose cohorts who were treated every four weeks, and 42% in the cohort treated every 12 weeks.

“There is clearly an urgent need to develop and deliver effective treatments for Alzheimer’s disease, a devastating disorder for which there currently are limited therapeutic options,” said C. Frank Bennett, Ph.D., chief scientific officer and franchise leader for neurological programs at Ionis. “We are encouraged by the topline results from this study of BIIB080, which demonstrate the potential of Ionis’ antisense technology to successfully target what we believe is a root cause of Alzheimer’s disease.”

Antisense therapies use short DNA-like molecules called antisense oligonucleotides. They selectively attach to target sequences in messenger RNA (mRNA), which can then inhibit or redirect splicing and inhibition of protein synthesis.

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