AstraZeneca and Eli Lilly’s collaboration in Alzheimer’s disease continues to make progress, as their AZD3293 drug is granted a fast-track review by the US FDA.
The amyloid-targeting BACE inhibitor drug has started a second late-stage trial and – if successful – could be the first treatment for Alzheimer’s that targets an underlying mechanism in the disease.
The FDA’s fast-track programme is designed to make effective drugs for serious diseases available more quickly and can speed up the review process.
AZ and Lilly are already carrying out one phase II/III placebo-controlled trial of AZD3293, called AMARANTH, that will enrol more than 2,000 patients with early-stage Alzheimer’s and should generate final results in 2019.
The new trial – called DAYBREAK-ALZ – will study the safety and efficacy of AZD3293 (also known as LY3314814) in around 1,900 people with mild Alzheimer’s dementia and will compare the BACE inhibitor to placebo over a three-year period, with results once again due in 2019.
BACE or beta-secretase is an enzyme involved in the conversion of amyloid precursor protein (APP) into amyloid beta, which is deposited as plaques in the brains of patients with Alzheimer’s disease.
Inhibitors of BACE are designed to interrupt this process, prevent the formation of plaques and – assuming the amyloid hypothesis of Alzheimer’s is correct – interrupt the cascade of events that lead to the degeneration of neurons in the disease.
Given the lengthy list of failed amyloid-targeting drugs for Alzheimer’s there is still a lot of risk in the development of BACE inhibitors but – for now at least – they have the best chance of becoming a new treatment class for the disease.
AZ and Lilly are in a race to market with Eisai/Biogen, Merck & Co and Amgen/Novartis, which all have BACE inhibitors in the clinic, but Lilly, Roche and Boehringer Ingelheim/Vitae Pharm have all scrapped candidates in recent years.
Merck’s MK-8931 (verubecestat) candidate is currently leading the pack as it started phase III in 2013, with interim data due in 2017 and final results in 2019. Eisai and Biogen’s E2609 has just started its pivotal trials programme. Amgen and Novartis are a little behind as their CNP520 compound is in phase I/II testing.