Eli Lilly recently revealed more than promising clinical trial results for its Alzheimer’s candidate, donanemab, showing that the drug slows Alzheimer’s by as much as 60 percent in mild cases. While safety concerns about the drug remain, Lilly is hoping for an FDA approval by the end of the year. But how does donanemab measure up against other Alzheimer’s-fighting monoclonal antibodies, namely Biogen and Eisai’s lecanemab?
Since the company revealed the encouraging results of its global 1,736-person, phase III trial at the recent Alzheimer’s Association International Conference (AAIC), the media have been heralding Eli Lilly’s Alzheimer’s drug candidate donanemab as a major breakthrough. The study results are indeed promising, showing that donanemab slowed disease progression by about a third, a rate that doubled to 60 percent in patients who are mildly impaired. The trial results also demonstrated that improvements continued to grow over time, even after patients had stopped taking the drug, findings that support the idea that treatment with donanemab would not necessarily be continual.
If approved, we believe donanemab can provide clinically meaningful benefits for people with this disease
Anne White, executive VP, Eli Lilly and president, Lilly Neuroscience
However, Lilly’s trial results were less conclusive for later-stage patients, making a case for early diagnosis and treatment, and for patients with higher levels of tau, a protein linked to Alzheimer’s progression. Moreover, a number of safety concerns remain. The study showed that brain swelling occurred in more than 40 percent of patients, brain bleeding occurred in 31 percent and as a result, three trial participants died.
The company published the complete study results in JAMA after initially revealing partial results in May and filed for a traditional FDA approval it expects by the end of the year. “If approved, we believe donanemab can provide clinically meaningful benefits for people with this disease and the possibility of completing their course of treatment as early as 6 months once their amyloid plaque is cleared,” said Anne White, executive vice president of Eli Lilly and Company and president of Lilly Neuroscience.
Lilly is seeking other global approvals and has already begun submissions to additional regulators.
Slowing disease progression
According to the World Health Organisation (WHO) dementia effects more than 55 million people worldwide and Alzheimer’s disease as the most common form of dementia is estimated to contribute to 60–70 percent of those cases. The fact that there is no cure for Alzheimer’s and treatments such as Eisei and Pfizer’s cholinesterase inhibitor, donepezil, have focused mainly on managing symptoms have led researchers to pursue treatments aimed at stopping or at least delaying the progression of the disease.
Along these lines, drugmakers have been looking to target the clumps of the protein beta-amyloid known as plaques that are a characteristic sign of the disease with medicines known as monoclonal antibodies like Lilly’s donanemab. These drugs mimic the antibodies the body naturally produces as part of the immune system’s response to foreign invaders or vaccines.
When the FDA granted accelerated approval in 2021 for Biogen and Eisai’s aducanumab, the first therapy to demonstrate that removing beta-amyloid from the brain can actually reduce cognitive and functional decline in people living with early Alzheimer’s, the director of the FDA’s Center for Drug Evaluation and Research Patrizia Cavazzoni expressed the hope placed on this new kind of therapy: “Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
But aducanumab’s side effects, namely asogenic oedema of the brain leading to microbleeds, and its exorbitant cost have led to disappointment and controversy and the drug has never gained market traction. Administered in the form of monthly infusions, initially had an estimated cost of about USD 56,000 per year, later reduced to USD 28,000, a price tag which is still too high for most.
The key contender to Lilly’s Alzheimer’s candidate is Biogen and Eisai’s second monoclonal antibody effort, lecanemab (Leqembi), a treatment that reached the finished line first. Approved under the FDA’s accelerated approval pathway at the beginning of this year, earlier this month lecanemab became the first Alzheimer’s treatment shown to reduce the rate of disease progression to gain a traditional approval from the American regulatory body.
Although Biogen and Eisai managed to get there first, trial results for lecanemab showed that it reduced cognitive decline by 27 percent as opposed to Lilly’s 35 percent and while the price of donanemab is still unknown, treatment with lecanemab remains costly with annual treatment averaging at around USD 26,500 per patient.