AstraZeneca to work with Lilly on Alzheimer's drug

AstraZeneca has enlisted the help of Lilly in the development of its new Alzheimer's candidate AZD3293.

The drug is an oral beta secretase cleaving enzyme (BACE) inhibitor, which the companies plan to bring into phase 2/3 trials to test in patients with early Alzheimer's disease.

The new alliance is the latest chapter in Lilly's dogged 25 year pursuit of a breakthrough in Alzheimer's disease – an area in which it and other companies have seen failure after failure of drug candidates.

AstraZeneca will receive $500 million from Lilly in development and regulatory milestone payments, and the companies will share all costs equally for the development and commercialisation of AZD3293, as well as any net global revenues post-launch.

Lilly will lead clinical development of AZD3293, working with researchers from AstraZeneca's Innovative Medicines Unit for neuroscience, while AstraZeneca will be responsible for manufacturing.

The alliance makes sense for AstraZeneca, which has limited experience in the Alzheimer's field, and for Lilly, which has seen billions in R&D funding on the disease come to nought so far.

Lilly halted development of its own BACE inhibitor LY2886721 in June 2013 because of abnormal liver tests in some patients in phase 2 trials. However it is thought that the problems were not related to the BACE mechanism, and Lilly has been keen to pursue the class.

Lilly and AZ have a rival in the BACE field – Merck's MK-8931 is currently in a phase 2/3 study treating patients with mild to moderate Alzheimer's.

BACE offers hope

Big pharma companies are hoping that BACE could offer a breakthrough where other mechanisms for tackling the disease have failed.

Lilly's gamma secretase inhibitors semagacestat was a high profile failure in August 2010, with data suggesting that it even worsened the disease: trial data showed patients taking it experiencing greater decline in cognitive function than those on placebo.

Bristol-Myers Squibb's avagacestat came to a similar dead end in December 2012. Other candidates – including Pfizer and J&J's amyloid-targeting antibody bapineuzumab have crashed out of development in the last few years.

Lilly's solanezumab is in the same class as Pfizer and J&J's drug, but despite failing to hit its primary endpoints, the company has kept the development programme alive. Analysis of the data showed it helps some patients with mild Alzheimer's, leading scientists believe that the drug could be effective when the disease is caught in its earliest stages.

The only other molecule Lilly has in its clinical pipeline is in phase I, and is called N3p-G-Aβ, another monoclonal antibody targeting beta amyloid.

Alzheimer's disease is characterised by the accumulation of amyloid plaque in the brain, which is comprised of peptides called amyloid beta. BACE is an enzyme associated with the development of amyloid beta. Inhibiting BACE is expected to prevent the formation of amyloid plaque and eventually slow the progression of the disease.

"Alzheimer's disease is one of the biggest challenges facing medical science today and BACE inhibitors have the potential to target one of the key drivers of disease progression," said Mene Pangalos, executive vice president, Innovative Medicines & Early Development at AstraZeneca.

Pangalos said that the combining of scientific expertise and sharing of risks and cost would allow them to accelerate AZD3293's development.

"What's more, this alliance will enable AstraZeneca to further sharpen our strategic focus on core therapeutic areas, while leveraging external collaborations to maximise the potential of the strong science we have in our growing pipeline," he concluded.

"Lilly has been committed to research in Alzheimer's disease for more than 25 years, and we're dedicated to developing new medicines that can change and modify the course of this devastating disease," said David Ricks, president, Lilly Bio-Medicines.

"Lilly's pipeline of potential medicines and diagnostic agents targeting the known hallmarks of the disease has been bolstered today by this alliance with AstraZeneca, which shares our passion to bring new medicines to patients suffering from this debilitating illness. This alliance moves us one step closer to achieving our goal of making Alzheimer's dementia preventable by 2025."

The US company's drive to find a breakthrough in Alzheimer's has a personal element for its head of R&D, Jan Lundberg, who wrote in pharmaphorum in July about how he lost his mother to the illness.

There remains considerable debate about whether the 'amyloid hypothesis' can ever yield a viable treatment for the disease, especially as the condition's exact mechanism remains a mystery. Other companies are pursuing different routes, including the small biotech TauRx, which is investigating the role of tau protein in the brain.