Alnylam, Biogen silence genes, building noise behind data on new approaches to Alzheimer's

Is gene silencing the future of Alzheimer’s disease treatment? Alnylam and Biogen presented first drafts of their answer to that question this week by publishing early-phase data on their respective RNAi and antisense approaches to treating the neurodegenerative disease. 

The two companies are using different technologies and pursuing different targets. Alnylam, through a partnership with Regeneron, is studying an RNAi candidate that is intended to suppress the production of amyloid precursor protein (APP) and thereby slow the formation of amyloid deposits. The program is the first to use an Alnylam technology that is designed to enable delivery to the central nervous system.

Biogen’s candidate is an antisense oligonucleotide that is designed to silence the gene encoding for tau, another protein implicated in Alzheimer’s. Since licensing the asset from Ionis in 2019, Biogen has begun to generate clinical data to show the treatment reduces total tau levels. 

Alnylam and Biogen used the Clinical Trials on Alzheimer’s Disease (CTAD) conference to share updated data on their candidates. The Alnylam presentation featured updated data on the 20 patients with early-onset Alzheimer’s who enrolled in the first part of a phase 1 trial of the RNAi candidate, ALN-APP. Alnylam shared earlier cuts of the data in April and July.

The updated data show the reductions in soluble APPα and soluble APPβ continued to tail off. Alnylam originally said median decreases of both biomarkers of 70% or more persisted for at least three months. By six months, the reductions in APPα and APPβ were greater than 55% and 65%, respectively. The latest, 10-month data show mean reductions in APPα and APPβ of 33% and 39%, respectively.

Alnylam saw those responses after administering a single dose. The multiple-dose part of the study is now underway in Canada and is cleared to start in the Netherlands and the U.K. However, that stage of the study remains on partial hold in the U.S. because of data from nonclinical chronic toxicology studies. 

Biogen used its session to present data from a phase 1b trial of its antisense oligonucleotide BIIB080. The drug candidate, which CEO Christopher Viehbacher has allocated more resources to, was the subject of a Nature Medicine paper earlier this year. The paper covered the main phase 1b results. 

In its CTAD presentation, Biogen shared a look at early data on measures of cognition and function. The trends favored BIIB080, with Biogen using the results of other studies as an external control to show the candidate may have positive effects on scores on the clinical dementia rating scale, mini mental state examination and functional activities questionnaire. Biogen is enrolling patients in a phase 2 trial.