Biogen, Ionis trumpet Alzheimer's data, but shares dip

Biogen and Ionis have revealed the first clinical results with tau-targeting Alzheimer's drug candidate diranersen, showing it was able to slow cognitive decline, but shares in both companies were affected by some misgivings about the data.

The phase 2 CELIA study in subjects with early Alzheimer's, presented at the Alzheimer's Association International Conference (AAIC) in London, revealed that treatment with diranersen was associated with a 26% slower decline in cognitive function compared to placebo at week 76.

That level of efficacy is in the same ballpark as the modest activity seen with current amyloid-targeting drugs for Alzheimer's, Eisai/Biogen's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab).

That raises the hope that combining a tau-acting drug with an amyloid drug could improve efficacy, particularly as other tau agents have struggled to show clinical efficacy in trials. Unlike other candidates that have focused on targeting extracellular tau, which forms the characteristic neurofibrillary tangles seen in Alzheimer's, diranersen is designed to reduce both intracellular and extracellular tau.

There was a ⁠50%-65% reduction in tau across all the doses studied in CELIA, based on brain imaging and spinal fluid measures, showing the drug was acting as intended.

Dose-response data draws attention

What seems to have concerned investors was the lack of a dose-response relationship in the data. The strongest response – measured using the CDR-SB scale – was seen with a dose of 60 mg administered intrathecally every six months.

Two other doses – 115 mg every six months and 115 mg every three months – resulted in a slowing in cognitive decline by 14% and 9%, respectively. That meant that one of the main objectives of the trial, demonstrating a dose response, was not met.

Shares in Biogen – which has just won a critical new FDA approval for a new Leqembi formulation – were trading down around 8% at the time of writing, while Ionis weakened by around 2.5%.

Ionis' chief development officer, Holly Kordasiewicz, said the results "provide important new insights into the potential of diranersen to markedly lower all forms of tau and meaningfully improve outcomes in early Alzheimer's disease."

Ionis and Biogen said they now intend to press ahead with a phase 3 programme for diranersen, which should get underway next year and could generate results around the end of the decade.

Biogen took an option on co-development rights to diranersen (also known as BIIB080 or IONIS-MAPTRx) in 2019, part of a wide-ranging neurology collaboration that has also generated spinal muscular atrophy (SMA) therapy Spinraza (nusinersen) and Qalsody (tofersen) for amyotrophic lateral sclerosis (ALS).

Photo by Pascal van de Vendel on Unsplash