Lilly awaits results for alternative amyloid drug in Alzheimer’s

In the next few weeks, Eli Lilly will report the first clinical data on a drug that represents a new approach to the treatment of Alzheimer’s disease (AD).

The data for LY3002813 will be the first test of the potential for antibodies as a passive immunisation against pyroglutamate- amyloid beta (pGlu-Abeta), a target that relates to but diverges from the prevailing amyloid hypothesis of Alzheimer’s pathology.

While the conventional amyloid hypothesis holds that the formation of amyloid plaques is a primary cause of the neuronal destruction in AD – with other features of the disease such as the formation of neurofibrillary tangles stemming from that – there is another school of thought emerging.

Some scientists believe the amyloid pathway outside the cell is a consequence of disruption that occurs within neurons, and interrupting this intracellular pathway could provide an alternative to current amyloid-targeting drugs that have had disappointing results in clinical trials.

pGlu-Abeta peptides tend to be found within neurons and accumulate in the brain at the earliest stages of AD, even before the appearance of clinical symptoms. They are also thought to be much more toxic to neurons than other amyloid-beta peptides.

The Lilly data is from a phase I trial, so will be aimed mainly at showing the safety of LY3002813 at various doses. It does however include both healthy people and patients with mild cognitive impairment due to AD, so could provide some clues about the drug’s activity.

The trial started in May 2013 and is due to complete in September 2016, with an interim look at data due before the end of the year, according to analysts at Edison. Lilly is also looking at combining LY3002813 with its BACE inhibitor LY3314814, which is in Phase II/III trials and is partnered with AstraZeneca.

The results will have a direct relevance to other companies working on pGlu-Abeta and particularly Germany’s Probiodrug, which has an antibody called PBD-C06 in preclinical development.

Probiodrug’s lead candidate PQ912 also targets pGlu-Abeta but via a different mechanism – it is a small-molecule inhibitor of glutaminyl cyclase, an enzyme involved in the formation of the pyroglutamate form. This drug has already been shown to be safe in a Phase I trial and Phase II results are due in the middle of 2016, according to Edison.

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