FDA Approves Lilly’s Kisunla™ (donanemab-azbt) for Early Symptomatic Alzheimer’s Disease Treatment

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As a company also involved in research for Alzheimer’s disease both from the DDS and API perspective, we cheer for this news!

The U.S. Food and Drug Administration (FDA) has approved Kisunla™ (donanemab-azbt), a once-monthly injection (350 mg/20 mL) for IV infusion developed by Eli Lilly and Company.

Kisunla is designed to treat adults with early symptomatic Alzheimer’s disease (AD), which includes mild cognitive impairment (MCI) and mild dementia stages of AD, with confirmed amyloid pathology. This is the first and only amyloid plaque-targeting therapy that allows stopping treatment when amyloid plaques are cleared, potentially reducing costs and the number of infusions needed.

FDA approves new drug to treat Alzheimer’s disease  (nbcnews.com)

FDA-Approved Alzheimer’s Medications

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⚫ Alzheimer’s disease takes a toll on not just the people suffering from the disease but also on their loved ones and caregivers in a way that almost no other illness does.

⚫ The Alzheimer’s disease market is projected to experience robust growth at a compound annual growth rate of 20% from $2.2 billion in 2020 to $13.7 billion in 2030!

🔶 Drug Development Pipeline:
🔸 187 current trials assessing 141 unique drugs
🔸 Phase 3: 36 drugs
🔸 Phase 2: 87 drugs
🔸 Phase 1: 31 drugs

🔷 Phase 3 has 36 agents in 55 trials:
🔹 DMT*-Biologics: 9 (25%)
🔹 DMT*-Small molecules: 15 (42%)
🔹 Putative cognitive-enhancers: 5 (14%)
🔹 Neuropsychiatric symptoms: 7 (19%)
*DMT stands for disease-modifying therapies

🔶 Most Common Targets:
🔸 Transmitter receptors, amyloid, synaptic function, and inflammation

🔷 58 new drugs have entered the pipeline in the past year!
🔷 28% of candidate therapies are repurposed from other diseases!

⚫Despite the hype, controversy, and occasional scandal surrounding the approval of Alzheimer’s drugs, and the disappointing reports of the ineffectiveness of recently approved drugs, many companies are still dedicating time and resources to finding a potential cure for this debilitating disease. This gives hope that the future is bright for those living with Alzheimer’s.

🔶 Learn more:
🔸 Alzheimer’s disease drug development pipeline: 2023 – Cummings – 2023 – Alzheimer’s & Dementia: Translational Research & Clinical Interventions – Wiley Online Library
🔸 Alzheimer’s Drug Market To Hit $13B As FDA Approvals And Insurance Coverage Escalate (forbes.com)

Great collection from Maryam Daneshpour

US FDA grants standard approval of Eisai/Biogen Alzheimer’s drug

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Eisai and Biogen’s Leqembi won a coveted standard approval nod from the U.S. Food and Drug Administration on Thursday, the first Alzheimer’s treatment to achieve that goal, clearing the way for wider insurance coverage of the drug.
The FDA decision marks a new milestone for a fatal disease that has eluded drugmakers’ efforts for decades. Trial data showed that the treatment slows the progression of the brain-wasting disease by 27% for patients in the earliest stages of Alzheimer’s.
The FDA also placed its strongest “boxed” safety warning on Leqembi’s label, flagging the risk of potentially dangerous brain swelling for Alzheimer’s drugs in the same class.
Leqembi is an antibody designed to remove sticky deposits of a protein called amyloid beta from the brains of Alzheimer’s patients.
Leqembi received “accelerated” FDA approval in January based on its amyloid-clearing ability, but the U.S. government’s Medicare health plan for people aged 65 and over had restricted coverage only to patients in a clinical trial.
Standard approval means that Leqembi will now be covered, although the Centers for Medicare and Medicaid Services (CMS) is linking reimbursement to patient participation in a health agency database, known as a registry. Since Alzheimer’s is a disease of aging, most U.S. patients are insured by Medicare.

The official announcement is on reuters.com!

Effect of Cosolutes on the Aggregation of a Tau Fragment: A Combined Experimental and Simulation Approach

carbohydrates

Having an interest in the applications of novel carbohydrates in neurodegenerative diseases, we applaud this paper on the aggregation of Tau fragments in the presence of different cosolutes, including urea, TMAO, sucrose, and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD).
The intrinsically disordered protein Tau represents the main component of neurofibrillary tangles that are a hallmark of Alzheimer’s disease and is considered to be important for the formation of the β-structure core of the fibrils. 
The remarkable ability of HPβCD to inhibit aggregation represents an extremely promising result for future applications, especially considering the widespread use of this molecule as a drug carrier to the brain and as a solubilizer/excipient in pharmaceutical formulations.
Andrea Arsiccio, Xikun Liu, Pritam Ganguly, Steve Buratto, Michael Bowers, and Joan-Emma Shea

See the full article here: Effect of Cosolutes on the Aggregation of a Tau Fragment: A Combined Experimental and Simulation Approach

Lilly drug slows Alzheimer’s by 35%, bolstering treatment approach

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Lilly’s Alzheimer’s drug donanemab slows cognitive decline by 35% in PhIII
An experimental Alzheimer’s drug developed by Eli Lilly and Company slowed cognitive decline by 35% in a late-stage trial, providing what experts say is the strongest evidence yet that removing sticky amyloid plaques from the brain benefits patients with the fatal disease.
Lilly’s drug, donanemab, met all goals of the trial: It slowed the progression of Alzheimer’s by 35% compared to a placebo in 1,182 people with an early-stage disease whose brains had deposits of two key Alzheimer’s proteins, beta-amyloid as well as intermediate levels of tau, a protein linked with disease progression and brain cell death.

See the article on reuters.com: Lilly drug slows Alzheimer’s by 35%, bolstering treatment approach

Cyclo Therapeutics Announces First Patient Dosed in Phase 2b Study of Trappsol® Cyclo™ for the Treatment of Early Alzheimer’s Disease

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Cyclo Therapeutics, Inc. announces first patient dosed in Phase 2b study of Trappsol® Cyclo™ for treating early Alzheimer’s disease.

Trappsol® Cyclo™ is the Company’s proprietary formulation of hydroxypropyl beta-cyclodextrin. In multiple clinical studies, it has shown encouraging results in effectively managing the transportation of cholesterol, a known defect in neurodegenerative diseases. Many known risk factors for Alzheimer’s disease are associated with cholesterol metabolism.

Cyclo Therapeutics is currently testing the same investigational Trappsol® Cyclo™ drug in Phase 3 clinical trial (TransportNPC™) and a long-term extension study for the treatment of Niemann-Pick disease Type C1, a rare, fatal, and progressive genetic disorder. Taking the place of the defective NPC1 protein, Trappsol® Cyclo™, with its cyclic structure, facilitates the transport of accumulated cholesterol out of cellular lysosomes so it can be further processed and excreted out of cells. With the biological similarities demonstrated between Niemann-Pick disease Type C1 and Alzheimer’s disease, including cholesterol accumulation in regions of the brain, elevated levels of Tau in cerebrospinal fluid (“CSF”), and amyloid plaques in the brain, the Company believes Trappsol® Cyclo™ has significant potential to be an effective treatment option for Alzheimer’s disease.

Read the full announcement here

APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

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Understanding the mechanism of action is crucial in order to develop truly efficient cyclodextrin-based actives. Massachusetts Institute of Technology’s study on Alzheimer’s disease reveals correlations between APOE4, cholesterol transport, and therapeutic opportunities for CDs.
Important study Joel Blanchard, Li-Huei Tsai et al.

See the full article on nature.com

Effects of Hydroxypropyl-Beta-Cyclodextrin on Cultured Brain Endothelial Cells

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Heartwarming to see such important findings published by Hungarian researchers on the effects of Hydroxypropyl-beta-cyclodextrin on Cultured Brain Endothelial Cells. Cytotoxicity, permeability, and cellular internalization of HPBCD on primary rat and immortalized human (hCMEC/D3) brain capillary endothelial cells were investigated, which can help to develop new strategies for improved HPBCD effects after systemic administration.

See the full article

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New clinical trial upcoming using cyclodextrin as active

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Cyclo Therapeutics, Inc. sponsors Phase II trial for early Alzheimer’s disease. The study will enroll approximately 90 male and female patients aged 50 to 80 years who will be given a minimum active dose of 500 mg/kg of Trappsol Cyclo (equivalent to 18,500 mg/m2) as an intravenous (IV) infusion once every 28 days for 6 months.
We wish the best of success to our colleagues at Cyclo Therapeutics and hope this therapy will prove useful for the benefit of these patients.
Having programs ourselves in developing NCEs for neurodegenerative diseases, we find this study particularly essential.

Read more about the clinical trial here