Lilly touts new Kisunla regimen that reduces side effects

Eli Lilly says a new starting dose regimen for its Alzheimer's disease therapy Kisunla reduces the risk of side effects that have stood in the way of approvals and reimbursement decisions for drugs in its class.

Simply shifting one vial of the anti-amyloid antibody from the first infusion to the third infusion of the titration phase of dosing – the period used to achieve therapeutic levels in the body – is enough to lower the incidence of a potentially serious side effect known as ARIA-E, according to the company.

The data comes from the phase 3b TRAILBLAZER-ALZ 6 study, which showed that the modified Kisunla (donanemab) regimen reduced the risk of ARIA-E over 24 weeks to 14% from 24% in the pivotal trial that supported the approval of the current dosing regimen – a 41% reduction.

There was no difference between the two dosing regimens in their ability to reduce amyloid plaques and levels of tau protein (P-tau217), suggesting efficacy is not affected by the change, said Lilly in a statement.

ARIA-E (amyloid-related imaging abnormalities with oedema/effusion), as well as a related side effect to do with small bleeds in the brain known as ARIA-H, tend to occur early on in treatment with Kisunla and other anti-amyloid drugs and can be life-threatening.

In the new study, there was also a larger 67% reduction in ARIA-E among patients with a pair of APOE4 mutations, a group considered to be at a higher risk of these side effects.

Kisunla has been approved in several countries, including the US, Japan, and GB, but failed to get the go-ahead for coverage by the NHS in the latter market because its modest efficacy was considered to be outweighed by its risks and the costs associated with managing them.

Similar concerns have also been raised with rival anti-amyloid drug Leqembi (lecanemab) from Eisai/Biogen and have blocked its approval in the EU and Australia, as well as reimbursement approval in GB.

Lilly will be hoping that the new titration regimen for Kisunla could tip the risk:benefit balance for its drug in favour of authorisations and help to drive uptake in the markets where it is already available. Meanwhile, it could also help offset concerns that the rate of ARIA-E and ARIA-H are a little higher with Kisunla than with Leqembi.

The company said it plans to submit the TRAILBLAZER-ALZ 6 data to regulators in the hope of updating the label for Kisunla.

"Lilly is committed to continuing research to optimise therapy for patients with Alzheimer's disease," commented Mark Mintun, head of neuroscience R&D at the pharma group.

"The modified titration could offer continued convenience of once-monthly dosing and limited duration treatment, while also reducing ARIA-E and maintaining similar amyloid plaque removal," he added.