Biogen’s Alzheimer’s Disease Drug Safe, Effective in Trial

Biogen recently announced that its Alzheimer’s disease drug, BIIB080, was safe and well-tolerated in patients with mild disease. The drug was developed in partnership with Ionis Pharmaceuticals.

The Phase 1, placebo-controlled clinical trial showed robust and dose-dependent lowering of tau protein in cerebrospinal fluid (CSF) over the three-month treatment period. These results were sustained for six-months post-treatment. 

Specifically, researchers found a 30 percent reduction in the low-dose group, a 40 percent reduction in the medium-dose group, and a 49 percent reduction in the high-dose group.

Total-tau in the CSF continued to decline 16 weeks post-last dose in patients treated with BIIB080 in high dose four-week and 12-week dose groups, researchers explained. Overall, patients experienced a 55 percent and 49 percent reduction from baseline, respectively. 

“Biogen is deeply committed to the development of novel treatments for patients with Alzheimer’s disease. This commitment extends across multiple modalities, including antisense oligonucleotides, as with BIIB080,” Alfred Sandrock, Jr, MD, PhD, head of research and development at Biogen, said in the announcement. 

“Biogen is encouraged by the results of this trial, and we look forward to our continued research in future clinical studies with this promising investigational asset,” Sandrock continued. 

BIIB080 is an investigational antisense therapy designed to target microtubule-associated protein tau mRNA and prevent tau protein production. Researchers explained that aggregated, hyperphosphorylated tau may be a key driver of neurodegeneration in Alzheimer’s disease.

The Phase 1b first-in-human study assessed the safety and tolerability of multiple intrathecal bolus administration of BIIB080. 

Part 1 of the study enrolled 46 patients with mild Alzheimer’s disease with a three-month treatment period and a six-month PT period, while the part 2 extension study has a 12- month treatment evaluation period and a four-or six-month PT period. 

In the first part of the study, all adverse events were mild to moderate, with no serious adverse events occurring in any patients that received BIIB080. Notably, there were no deaths, dose-limiting adverse events, or dosing discontinuations. 

Part 2 of the study is currently ongoing. 

“There is clearly an urgent need to develop and deliver effective treatments for Alzheimer’s disease. 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,” C. Frank Bennett, PhD, chief scientific officer and franchise leader for neurological programs at Ionis Pharmaceuticals, concluded. 

More than 11.3 percent of individuals 65 years of age and older has Alzheimer’s disease. Currently, there are a handful of FDA approved drugs to slow symptoms, including cholinesterase inhibitors and glutamate regulators.

In June, FDA approved Biogen’s Alzheimer’s disease drug, Aduhelm, to slow clinical decline in individuals living with the disease. 

The approval came after long speculation about the drug’s efficacy and after Biogen discontinued its ENGAGE and EMERGE trials in 2019 based on analysis results that showed that ENGAGE did not meet its primary endpoints. 

Overall trial results showed that Aduhelm administered as a monthly infusion was not better at slowing memory loss and cognitive impairment than placebo

Therefore, some doctors and scientists see FDA’s approval as premature because they aren’t convinced the drug actually works, given the mixed trial results over the years. 
Soon after the approval, three experts resigned from the FDA’s advisory committee, claiming that there was not enough evidence to support the approval and that FDA did not listen to the committee’s input and concerns before making its decision.