Editor’s Note: This is part 2 of a two-part package on the pipeline for Alzheimer’s disease drugs. Check out part 1.
While the controversy surrounding the FDA’s approval of Biogen’s adumanucab for Alzheimer’s disease continues, several other drug companies are developing their own therapies to prevent or slow the progression of the disease.
One of those new drugs, ALZ-801, began National Institute of Aging-funded Phase 3 trials on June 4. Unlike aducanumab or other drug candidates from Eisai, Eli Lilly and Roche, which attack amyloid plaque after it forms in the brain, biotech startup Alzheon, Inc. aims to help people with AD who have two copies of the ε4 allele of the apolipoprotein E gene (APOE4/4), a known risk factor for Alzheimer’s disease. The goal is to prevent plaque from forming in the first place or prevent additional plaque from forming in those who already show clinical symptoms of Alzheimer’s. ALZ-801 is also the only drug currently under investigation administered orally and which uses precision medicine strategy (factoring in individual genetics and lifestyle), according to the company. Continue reading
Eli Lilly recently announced that the FDA had granted a breakthrough therapy designation for donanemab, its investigational antibody therapy for Alzheimer’s disease. The designation means the FDA will expedite the drug’s development and review because it treats a serious condition, and early evidence has shown enough improvement on key clinical measures compared to other drugs on the market. This should mean it has a good chance of being effective in treating the condition.
Donanemab, also called N3pG, is an investigational antibody that targets a modified form of beta-amyloid, aiming to clear out plaques that have built up in the brain. Lilly’s Phase 2 trial, TRAILBLAZER-ALZ, studied the efficacy and safety of donanemab in patients with early, symptomatic Alzheimer’s. The results, which appeared in the May 6 New England Journal of Medicine, concluded that “donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed.” Continue reading
Part two of two parts; the first ran Thursday, June 10.
There’s still a great deal we don’t yet understand about aducanumab (brand name Aduhelm) or its longer-term effects. If early-stage Alzheimer’s disease is diagnosed in time for someone to begin taking the drug, are the potential adverse effects cumulative? Could long-term toxicity build up over time? How long might the drug stave off development of the plaque, and how long might it slow down the process of cognitive decline, if at all, and how will clinicians assess its benefit in patients? Continue reading
National Institute on Aging/National Institutes of HealthBeta-amyloid plaques and tau in the brain.
Part one of two parts; the second runs tomorrow, Friday, June 11.
You might think that the first new drug to treat Alzheimer’s in 18 years — and the first to treat underlying disease and not just symptoms — would be heralded by patients, families, and medical professionals alike. After all, the FDA’s approval on Monday of aducanumab (brand name Aduhelm) sounds like a tremendous breakthrough for the estimated 6 million Americans, and 50 million people globally, who suffer from the disease.
However, because of the supporting clinical data on its effectiveness, the drug has been controversial from the start. Drug maker Biogen actually halted its parallel Phase 3 studies, ENGAGE and EMERGE, because they failed to meet their primary endpoints. Those original endpoints were a change in the Clinical Dementia Rating-Sum of Boxes (CDR-SB), which is similar to a composite endpoint because it assesses improvement in multiple different domains. Continue reading