Lilly's tau drug for Alzheimer's flunks phase 2 test
Eli Lilly is still celebrating the FDA approval of its amyloid-directed Alzheimer's therapy Kisunla but has had less fortune with a candidate against tau, another well-established drug target for the disease.
In the company's second-quarter results call, Lilly's chief scientific officer Daniel Skovronsky revealed that orally active anti-tau drug LY3372689 – an O-GlcNAcase (OGA) inhibitor – failed a phase 2 study in early symptomatic Alzheimer's.
The experimental therapy didn't meet the primary endpoint of decreasing the change from baseline measured by the integrated Alzheimer's Disease Rating Scale (iADRS) compared to placebo, for either of the two doses tested.
"While this negative outcome is disappointing, we remain committed to tau as a high-conviction target in Alzheimer's disease and plan to continue studying tau biology," said Skovronsky on the call. At the moment, there are no other tau-directed candidates in Lilly's clinical-stage pipeline.
LY3372689 was designed to slow the accumulation of hyper-phosphorylated, insoluble tau aggregates in the central nervous system, which clump together to form neurofibrillary 'tangles', one of the hallmarks of Alzheimer's alongside the beta-amyloid plaques targeted by Lilly's recently approved Kisunla (donanemab) and Eisai/Biogen's Leqembi (lecanemab).
Tau tangles are also a feature of other neurodegenerative diseases, including Parkinson's and amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND).
Other companies looking at OGA inhibitors include Asceneuron, which raised $100 million in a Series C backed by Novo Holdings last month that will be used to fund mid-stage trials of its candidate ASN51. Biogen meanwhile reported phase 1 data with its BIIB113 candidate in healthy volunteers earlier this year and MSD/Alectos have an inhibitor called MK-8719 in preclinical testing.
Tau remains a popular target among Alzheimer's drug developers, although like the amyloid class has seen a lot of mixed clinical trial results. Lilly abandoned antibody-based tau inhibitor zagotenemab in 2021while earlier this year Roche handed back rights to its AC Immune-partnered candidate semorinemab both decisions coming after disappointing phase 2 results.
The wider tau-targeting pipeline meanwhile includes a handful of phase 3 candidates, including Eisai's antibody-based E-2814 and small-molecule drugs from Annovis Bio (buntanetap), BioVie (bezisterim), and TauRx (HMTM). The latter drug was filed for approval in the UK in July for the treatment of mild cognitive impairment and mild to moderate Alzheimer's.
Image by congerdesign from Pixabay
