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INDIANAPOLIS , July 17, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) presented full results from the Phase 3 TRAILBLAZER-ALZ 2 study showing that donanemab significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer's disease (AD). The data were shared at the 2023 Alzheimer's Association International Conference (AAIC) as a featured symposium and simultaneously published in the Journal of the American Medical Association (JAMA) . "The positive TRAILBLAZER-ALZ 2 data bring hope to people with Alzheimer's disease who urgently need new treatment options. This is the first Phase 3 study of a disease-modifying therapy to replicate the positive clinical results observed in a previous study," said Anne White , executive vice president of Eli Lilly and Company and president of Lilly Neuroscience. "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. We must continue to remove any barriers in access to amyloid-targeting therapies and diagnostics in an already complex healthcare ecosystem for Alzheimer's disease." Lilly previously announced that donanemab met the primary and all cognitive and functional secondary endpoints in the Phase 3 study. Submission to the U.S. FDA for traditional approval was completed last quarter with regulatory action expected by the end of the year. Submissions to other global regulators are currently underway, and the majority will be completed by year end. The TRAILBLAZER-ALZ 2 results support Lilly's application for regulatory approval to treat people with amyloid-positive early symptomatic Alzheimer's disease (either mild cognitive impairment or mild dementia), regardless of their baseline level of tau. TRAILBLAZER-ALZ 2 enrolled participants with a broader range of cognitive scores and amyloid levels than other recent trials of amyloid plaque-targeting therapies. Participants in TRAILBLAZER-ALZ 2 were stratified by their level of tau, a predictive biomarker for disease progression, into either a low-medium tau group (sometimes referred to as intermediate tau) or a high tau group, which represented a later pathological stage of disease progression. All participants were then assessed over 18 months using scales that measure both cognition and function, including the integrated Alzheimer's Disease Rating Scale (iADRS) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). As previously reported, among participants with low-medium levels of tau (n=1182), donanemab treatment significantly slowed decline by 35% on iADRS and 36% on CDR-SB. Among all amyloid-positive early symptomatic AD study participants (n=1736), treatment with donanemab significantly slowed decline by 22% on iADRS and 29% on CDR-SB. Additional data presented at AAIC reinforced that regardless of baseline clinical or pathological stage of disease, treatment with donanemab resulted in cognitive and functional benefits relative to placebo: A pre-specified subpopulation analysis of low-medium tau participants based on clinical stage showed greater benefit of donanemab in those at earlier stage of disease: In participants with mild cognitive impairment (n=214), donanemab slowed decline by 60% on iADRS and 46% on CDR-SB (for those with mild dementia due to AD, n=534, donanemab slowed decline by 30% on iADRS and 38% on CDR-SB, respectively). Similarly, a post-hoc subgroup analysis of low-medium tau participants based on age showed greater benefit of donanemab in patients under the age of 75: In participants under the age of 75 (n=542), donanemab slowed decline by 48% on iADRS and 45% on CDR-SB. In participants aged 75 or greater (n=551), donanemab slowed decline by 25% on iADRS and 29% on CDR-SB. Results were similar across other subgroups, including participants who carried or did not carry an ApoE4 allele. The overall treatment effect of donanemab continued to grow throughout the trial, with the largest differences versus placebo seen at 18 months. "These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer's disease may lead to greater clinical benefit," said Liana Apostolova , M.D., distinguished professor in Alzheimer's Disease research and professor in neurology, radiology, medical and molecular genetics at Indiana University School of Medicine , where she is associate dean for Alzheimer's disease research and directs the clinical core of the Alzheimer's Disease Center. "The delay of disease progression over the course of the trial is significant and will give people more time to do such things that are meaningful to them." Donanemab specifically targets deposited amyloid plaque and has been shown to lead to plaque clearance in treated patients. Treatment with donanemab significantly reduced amyloid plaque levels regardless of baseline pathological stage of disease. Among all participants, treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for participants on placebo. Participants were able to stop taking donanemab once they achieved pre-defined criteria of amyloid plaque clearance.* Approximately half of participants met this threshold at 12 months and approximately seven of every ten participants reached it at 18 months. In the earlier pathological stage of disease in participants with low-medium tau, treatment with donanemab resulted in 47% of participants with no progression at one year on the CDR-SB assessment, versus 29% on placebo. Those participants treated with donanemab also had a 39% lower risk of progressing to the next clinical stage of disease over the 18-month trial. This delay in progression meant that, on average, participants treated with donanemab had an additional 7.5 months before they reached the same level of cognitive and functional decline on CDR-SB compared to those on placebo. "People living with early, symptomatic Alzheimer's disease are still working, enjoying trips, sharing quality time with family – they want to feel like themselves, for longer," said Mark Mintun , M.D., group vice president Neuroscience Research & Development at Lilly, and president of Avid Radiopharmaceuticals. "The results of this study reinforce the importance of diagnosing and treating disease sooner than we do today." The incidence of amyloid-related imaging abnormalities (ARIA) and infusion-related reactions was consistent with the previous TRAILBLAZER-ALZ study. ARIA occurs across the class of amyloid plaque clearing antibody therapies. It is most commonly observed as temporary swelling in an area or areas of the brain (ARIA-E) or as microhemorrhages or superficial siderosis (ARIA-H), in either case detected by MRI, and these may be serious and even fatal in some cases. This risk should be managed with careful observation, monitoring with MRIs, and appropriate actions if ARIA is detected. Serious infusion-related reactions and anaphylaxis were also observed. Adverse Events Donanemab Group (n=853) Placebo Group (n=874) Any serious adverse event 17.4 % 15.8 % Overall death 1.9 % 1.1 % Death related to treatment 0.4 % 0.1 % Infusion-related reaction (IRR) 8.7 % 0.5 % Any ARIA (-E or -H) 36.8 % 14.9 % ARIA-E (asymptomatic) 17.9 % 1.9 % ARIA-E (symptomatic) 6.1 % 0.1 % ARIA-H 31.4 % 13.6 % For full TRAILBLAZER-ALZ 2 results, see the publication in JAMA. About TRAILBLAZER-ALZ 2 Study and the TRAILBLAZER-ALZ program TRAILBLAZER-ALZ 2 (NCT04437511) is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants ages 60-85 years with early symptomatic Alzheimer's disease (MCI or mild dementia due to Alzheimer's disease) with the presence of confirmed Alzheimer's disease neuropathology. The trial enrolled 1736 participants, across 8 countries, selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by PET imaging. Lilly previously announced and published in the New England Journal of Medicine (NEJM) results from the Phase 2 TRAILBLAZER-ALZ study in 2021. In addition, Lilly shared data from TRAILBLAZER-ALZ 4, the first active comparator study in early symptomatic Alzheimer's disease, at the 15th Clinical Trials on Alzheimer's Disease (CTAD) conference in 2022. Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, which is focused on preventing symptomatic Alzheimer's disease in participants with preclinical AD; TRAILBLAZER-ALZ 5, a registration trial for early symptomatic Alzheimer's disease currently enrolling in China; and TRAILBLAZER-ALZ 6, which is focused on expanding our understanding of ARIA through novel MRI sequences, blood-based biomarkers, and different dosing regimens of donanemab. About Lilly Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn. * Participants completed their course of treatment with donanemab once they reached a pre-defined level of plaque clearance. Average baseline amyloid levels were ~100 Centiloids for participants with early symptomatic Alzheimer's disease. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about donanemab as a potential treatment for people with early symptomatic Alzheimer's disease and the timeline for future readouts, presentations, and other milestones relating to donanemab and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study findings to date, that donanemab will prove to be a safe and effective treatment, or that donanemab will receive regulatory approval. For further discussion of these and other risks and uncertainties, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. SOURCE Eli Lilly and Company Posted: July 2023 Donanemab FDA Approval History

A closely watched experimental drug for Alzheimers disease slowed the decline patients typically experience by about half a year in a key clinical trial, according to new results released Monday.The drug, called donanemab, is being developed by Eli Lilly and works in a similar way as two other medicines recently approved in the U.S. to treat Alzheimers. These therapies are designed to break up clusters of amyloid beta, a mutated protein that forms toxic brain plaques and has long been viewed as a root cause of the disease.In May, Lilly announced donanemab succeeded in a large, late-stage study that enrolled more than 1,700 people with early forms of Alzheimers. The drug effectively cleared amyloid from the brain, and patients treated with it declined around 35% slower on a disease rating scale than those given a placebo. Encouraged by the results, Lilly said it would submit an approval application to the Food and Drug Administration before the end of June.On Monday, the company provided a more detailed look at the trial data during a presentation at the Alzheimer's Association International Conference, an annual research meeting. After a year and a half of treatment, donanemab delayed disease progression by roughly five to seven months in certain patients.We agree this is a starting point, but wow, what a starting point, Mark Mintun, Lillys head of neuroscience research and development, said during a press conference Monday.John Sims, another Lilly neuroscience executive, compared these initial amyloid-targeting therapies to drugs for diabetes. Diabetes doesnt have a cure, either, but it doesnt mean you cant have meaningful treatments, he said at the press conference.Along with its presentation, Lilly disclosed it had completed its approval application to the FDA and expects a verdict by the end of the year. The results were also published in the medical journal JAMA.Until recently, there were no medicines approved in the U.S. to treat the underlying cause of Alzheimers. That changed in mid-2021 with the conditional clearance of Biogen and Eisais Aduhelm, though use of the drug has been extremely limited due to conflicting data and controversy surrounding its high price.Biogen and Eisai have since secured full approval of another amyloid-targeting therapy, Leqembi, which is backed by more consistent clinical trial results and is expected to have much broader use.Donanemab, should it gain approval, would help affirm the prominent theory that mutated amyloid is a main driver of Alzheimers. This so-called amyloid hypothesis has faced increased scrutiny in recent years, due to the many failures of other experimental therapies.Lilly also examined the role played by tau, another protein tied to Alzheimers. Tangles of this protein usually grow in the brain as the disease advances, and Lilly focused its study analysis on people with low or intermediate levels.It was just a short year ago we were still arguing about how removing amyloid and tau might not have any benefit, Maria Carrillo, the Alzheimers Associations chief science officer, said during Mondays press conference. Now theres evidence that really will propel the entire field into looking into these other markers [of disease]. Its important to double down and not slow down.Though donanemab could become a valuable new option for some of the estimated 6 million Alzheimers patients in the U.S., it doesnt work for everyone. Participants who entered Lillys study with high amounts of tau, for example, didnt benefit from the drug, the fuller data showed.In the JAMA paper, the studys authors wrote that this outcome supports the hypothesis that a greater benefit from amyloid-lowering therapies may occur when initiated at an earlier disease stage.The degree of benefit offered by donanemab is also a matter of debate, particularly as Lillys drug, like Aduhelm and Leqembi, comes with the risk of brain swelling and bleeding. Three participants in Lillys trial with serious signs of these so-called ARIA side effects later died.Slowing progression by a quarter to a half a year as seen with donanemab allows for someone to remain in [mild cognitive impairment] or mild-stage dementia for just that much longer, wrote three physicians in an editorial published alongside the data.The modest benefits would likely not be questioned by patients, clinicians, or payers if amyloid antibodies are low risk, inexpensive, and simple to administer, they added. However, they are none of these.Alzheimers experts have argued that testing for amyloid and, in the case of donanemab, tau will add further costs to treatment and may stretch the resources of smaller treatment centers.Additionally, Lillys results are hindered by how few people of color were enrolled in its trial, and the cap on participants age of 85 years, limiting the data available for groups heavily impacted by the disease.Similar to previous trials of [Leqembi] and [Aduhelm], this donanemab trial does not provide sufficient evidence of safety or efficacy among people racialized as American Indian or Alaska Native, Asian, Black, or Hispanic, wrote Jennifer Manly, of Columbia University, and Kacie Deters, of the University of California, Los Angeles, in another JAMA editorial.Jonathan Gardner contributed reporting '