Lilly sets out its stall on donanemab as filing approaches

The FDA's approval of Biogen's Aduhelm for Alzheimer's disease has emboldened Eli Lilly to move forward plans to file its own candidate donanemab later this year, although it acknowledges it will have to overcome reservations about anti-amyloid drugs.

Lilly's chief scientific officer Dan Skovronsky said on the company's second-quarter results call that the results of the phase 2 TRAILBLAZER-ALZ study reported earlier this year, combined with safety data from the ongoing phase 3 TRAILBLAZER-ALZ 2 trial, should support a filing for accelerated approval before the end of the year.

Moreover, rapid progress in recruiting patients into the phase 3 study means that dosing could start within a few weeks and complete 18 months later, with "potential replicated clinical efficacy results expected in 2023".

"Replication is important to overcome scepticism in the field," said Skovronsky as he detailed a string of reasons why donanemab is a compelling candidate for Alzheimer's, and why using amyloid clearance as a surrogate marker for clinical efficacy – one criticism levelled at the Aduhelm (aducanumab) approval – is a valid approach.

"We believe donanemab clears plaque faster and deeper than previously seen with other therapies," he said on the call, adding that new TRAILBLAZER-ALZ data presented at last week's Alzheimer's Association International Conference (AAIC) showed a relationship between amyloid plaque reduction and slowing of cognitive decline.

The earlier readout from the trial showed a statistically significant reduction in cognitive decline with plaque reduction, although there did not seem to be a correlation between the degree of reduction and the cognitive benefit. At AAIC, it showcased a "more sophisticated" statistical analysis that showed a correlation.

Skovronsky also pointed to evidence that donanemab not only clears amyloid but also slows down the formation of tau protein clumps which has been linked to clinical benefit in previous studies.

Taken together, that "strongly supports the efficacy of donanemab and gives us confidence that the remarkable levels of amyloid plaque clearance achieved by donanemab could translate into a meaningful breakthrough for patients", he added.

The FDA has already awarded the drug with a breakthrough designation, meaning it will get a shorter review time after filing.

Lilly, Biogen and just about everybody with an interest in Alzheimer's care is now waiting with bated breath for the outcome of the Centres for Medicare & Medicaid Services (CMS) national coverage determination (NCD) for Aduhelm, amid concerns that the drug's $56,000 a year pricing could put a heavy burden on the US health system.

Lilly's chief executive David Ricks would not be drawn on Lilly's pricing plans for donanemab, saying merely that the company intends to "make sure that all of the people millions in the US who could qualify for it could access it on day one".

Skovronsky meanwhile said the NCD "is a clear opportunity to focus treatment on the patients most likely to benefit from amyloid plaque-reducing therapies".

"We hope that each drug will be evaluated by payers and prescribers based on its own data," he added.