Trial miss doesn't dent Biogen's faith in Alzheimer's drug

Biogen has decided to advance its tau-targeting Alzheimer's disease drug diranersen (BIIB080) into a phase 3 trial programme, despite a phase 2 trial missing its main efficacy measure.

In the 18-month CELIA trial, antisense-based diranersen achieved reductions in insoluble tau aggregates, which clump together to form characteristic neurofibrillary 'tangles' in the central nervous system of people with Alzheimer's, across all the doses tested, although there was no clear dose-response relationship.

The trial also pointed to a slowdown in cognitive decline, again evident across all doses of diranersen but without a dose-response relationship, as the greatest benefit was seen with the lowest dose tested. Moreover, it did not meet its primary endpoint, which looked at the change from baseline on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at week 76.

Undeterred, Biogen said this is the first randomised phase 2 trial of a tau-directed drug to deliver both "robust biomarker impact and cognitive benefit" in early Alzheimer's patients, adding that the data "give us the confidence to advance diranersen to registrational development."

There was no hard data in Biogen's statement on the results, so clinicians will be waiting for a presentation scheduled to take place at the Alzheimer's Association International Conference (AAIC), scheduled to take place in July in London, UK.

As with amyloid-targeting drugs – which saw dozens of failed trials before the first candidates made it through to market – anti-tau therapies have seen numerous setbacks in recent years.

Last November, for example, Johnson & Johnson reported that a phase 2b trial of its antibody candidate posdinemab failed to show any impact of the drug on cognitive decline and was abandoned.

Other tau-directed drugs that have delivered disappointing clinical results include Eli Lilly's antibody-based zagotenemab and small-molecule OGA inhibitor LY3372689, and Roche/AC Immune's semorinemab. Biogen also had a go at developing an antibody – gosuranemab – but abandoned that in 2021 after a phase 2 failure.

The CELIA results have been welcomed by the Alzheimer's Association, which said they represent "important progress" for the patient community.

"People living with Alzheimer's and their families deserve more treatment options, and the pace of progress is accelerating," said Joanne Pike, the organisation's president and chief executive.

While noting there is more to learn about what these results mean for people living with Alzheimer's, including the treatment's benefit and safety profile, she added: "We look forward to seeing additional data and results when they are presented."