Lilly’s Latest Alzheimer’s Drug Fails to Live Up to Hope in Phase III Trial

Eli Lilly has had a tough time in its search for an Alzheimer’s disease treatment this year, as the latest data released from the Phase III A4 study revealed that solanezumab was unable to slow cognitive decline in preclinical Alzheimer’s patients. Despite the setback, the company remains determined to make a breakthrough in the treatment of this debilitating condition.

John Sims, head of medical, global brand development at Lilly, announced in a statement that the company is halting clinical development of its asset, solanezumab. This decision comes after careful consideration of the current state of the asset.

The ground-breaking A4 trial enrolled more than 1,100 participants with evidence of amyloid plaque build-up in their brains but no clinical impairment. Its primary outcome was cognitive decline, as evaluated by the Preclinical Alzheimer Cognitive Composite (PACC), a tool that assesses episodic memory, timed executive function and global cognition. This was the first time a secondary prevention trial of this kind had been conducted, and the results could pave the way to earlier interventions and treatments for Alzheimer’s disease.

Solanezumab treatment had a slight, yet insignificant, effect on patients’ PACC scores, with an average drop of 1.69 points compared to placebo counterparts’ 1.4-point decrease.

Lilly’s candidate was unable to show a substantial improvement in secondary efficacy markers, including progression from preclinical to symptomatic Alzheimer’s disease. Despite the lack of success, Lilly remains optimistic in their pursuit of creating treatments for this debilitating condition.

Solanezumab is a revolutionary monoclonal antibody that has been developed to target amyloid proteins in order to combat early onset Alzheimer’s disease. Unlike other treatments currently in development such as donanemab and remternetug, solanezumab is uniquely designed to only bind to soluble monomeric forms of amyloid β, meaning it can only have an effect on amyloid proteins before they have a chance to form plaques in the brain.

In A4, participants in both the solanezumab and placebo arms saw a rise in amyloid plaques, with the former accumulating 12.1 centiloids and the latter 17.5 centiloids over the course of the study. This increase in deposits suggests that further investigation is needed to determine the effectiveness of solanezumab in combating the accumulation of amyloid plaques.

Reisa Sperling, M.D., neurologist at the Brigham and Women’s Hospital and A4 project director, believes we need to take a more aggressive approach to amyloid removal in preclinical Alzheimer’s, based on results suggesting it is a key driver of cognitive decline. “We may need to be more aggressive with amyloid removal even at this very early stage of disease,” she said in a prepared statement.

A Rough Three Months 

Lilly’s latest setback in its mission to create a successful Alzheimer’s treatment has been the failure of Phase III of its solanezumab trials. Despite the disappointment, the company remains determined to continue its search for a breakthrough to help those affected by this devastating disease.

In January, the FDA rejected the company’s attempt to gain accelerated approval of donanemab, its most advanced Alzheimer’s asset. The regulator’s complete response letter pointed to a need for more data to establish the antibody’s safety and efficacy, leaving the company’s plans in limbo.

Lilly stood behind donanemab’s expedited regulatory application with their Phase II TRAILBLAZER-ALZ study, boasting over a hundred participants. However, the trial allowed participants to cease treatment once their brain amyloid plaques had reached a certain level, resulting in fewer than a hundred individuals being treated with donanemab for a full twelve months.

In the upcoming months, Lilly is set to receive topline data from the TRAILBLAZER-ALZ 2 trial, which it will use to apply for traditional approval of donanemab – a promising breakthrough in Alzheimer’s treatment.

The FDA’s decision to approve donanemab for clinical trials has been met with mixed reception, with some experts praising the decision for allowing more research into the drug’s effects on overall function, despite the resulting dip in Lilly’s stocks. Although the drug has demonstrated the ability to clear amyloid plaques, its effects on overall function have yet to be established.

Lilly is taking the fight against Alzheimer’s disease to the next level with their new remternetug molecule. Through clinical trials, the molecule has been found to effectively bind to amyloid deposits in the brain, and is now entering Phase III for early stage treatments. This exciting development could revolutionize the way we tackle this devastating disease.

Leave a Comment