Lilly restates Alzheimer's disease pipeline hopes

US-based pharmaceutical Eli Lilly & Co has revealed its hopes for two experimental treatments for Alzheimer's disease (AD), which it says could significantly augment profits derived from its current central nervous system (CNS) portfolio.

Lilly's CEO Sidney Taurel said he was excited about the pipeline drugs, which are currently in phase II trials. They work by dissolving amyloid plaques, which are structural abnormalities found in the brains of AD patients.

A successful AD drug has yet to materialise on the world market. If such a treatment did eventually materialise, however, it would not only benefit the growing elderly population in industrialised nations, but also rack up huge profits for the company in question, hence Lilly's excitement

One of Lilly's drugs, LY2062430, is undergoing a multiple-dose safety study in subjects with mild-to-moderate AD and single-dose safety in healthy volunteers. The study is expected to complete in March 2008. It is a long way from phase II to marketed status, however, and much can and often does go wrong.

Competitors
Other companies are not standing by passively, of course. A phase III study sponsored by US-based Martek Biosciences and the US National Institute on Aging is testing whether the omega-3 fatty acid, docosahexaenoic acid, can slow cognitive and functional decline in people with mild to moderate AD.

Also, a phase II study instigated by Memory Pharmaceuticals is testing whether its investigational compound MEM 1003, which helps regulate brain calcium levels, is potentially useful in mild-to-moderate AD.

Myriad Genetics is currently evaluating a phase III trial of its compound, Flurizan, which the company calls the first in a new class of drugs known as selective amyloid-lowering agents, or SALAs, which are also under investigation at other companies.

While new treatment avenues are causing some excitement, existing treatments are also being revisited to boost their efficacy. The five currently FDA-approved AD drugs are Eisai and Pfizer's Aricept; Novartis' Exelon patch; J&J's Razadyne; and Forest Lab's Namenda. Despite gaining first approval from the FDA, First Horizon Pharmaceutical's Cognex is rarely prescribed because it is associated with increased risk of liver damage.

The first four drugs are cholinesterase inhibitors, which work by preventing the breakdown of acetylcholine. Namenda works by regulating the activity of glutamate in the brain and nervous system.

Vaccines offer promise
US-based Wyeth and Ireland headquartered Elan initially teamed up to conduct a clinical trial of a vaccine which stimulates beta-amyloid antibodies in the hope that they will prevent the formation of AD plaques.

The trial was abandoned when several of the participants developed severe inflammation of the brain. Researchers noticed, however, that patients did show a significant slowing of cognitive decline. Both firms are now testing a revised version of the vaccine which is hoped will not cause inflammation.

Merck is testing an AD vaccine (V950) in a phase I trial. The aim is to prevent the build-up of beta-amyloid before it damages the brain's neuronal communication system.

Evidence-based medicine must support new treatments
The recent decision by the National Institute for Clinical Excellence (NICE), the cost-effectiveness watchdog organisation for the UK's National Health Service (NHS), to restrict use of AD drugs in all but the most seriously ill patients, has upped the stakes to make sure that new AD drugs deliver by using evidence-based medicine criteria to prove effectiveness.

As NICE's CEO, Andrew Dillon, said at the time: "We have to be honest and say that based on all the evidence, including data presented by drug companies, our experts have concluded that these drugs do not make enough of a difference for us to recommend their use for treating all stages of AD."