What is the biological target and mechanism of action of solanezumab?

What is the biological target and mechanism of action of solanezumab?

Mechanism of action Solanezumab binds the amyloid-β peptides that aggregate and form plaques in the brain that are an early pathological feature of Alzheimer’s disease. Solanezumab binds the central epitope of monomeric amyloid-β, KLVFFAED, (PDB ID 4XXD) with picomolar affinity.

How does Gantenerumab work?

Gantenerumab preferentially interacts with aggregated brain Aβ, both parenchymal and vascular. The antibody elicits phagocytosis of human Aβ deposits in AD brain slices co-cultured with human macrophages. It also neutralizes oligomeric Aβ42-mediated inhibitory effects on long-term potentiation in rat brains.

When will BAN2401 be available?

The trial is set to run until 2024. In February 2020, the Alzheimer’s Therapeutic Research Institute announced that the Alzheimer’s Clinical Trial Consortium (ACTC) would conduct a large BAN2401 study co-funded by the NIH and Eisai (press release). Called AHEAD 3-45, this Phase 3 study started in July 2020.

What are BACE inhibitors?

Expert commentary: BACE inhibitors inhibited robustly, and dose-dependently, Aβ formation in cerebrospinal fluid of AD patients, but without cognitive, clinical, or functional benefit in large RCTs. BACE inhibition may be not sufficient to decrease brain Aβ plaques and aggregates.

What is Elenbecestat?

Elenbecestat is a small-molecule inhibitor of BACE, aka the β-secretase enzyme. It was developed with the rationale of interfering with the amyloid cascade upstream of Aβ peptide generation.

What is LMTX?

LMTX (methylthioninium, also known as TRx0237 and LMTM) is an investigational therapy being developed by TauRx Pharmaceuticals to treat the symptoms of Alzheimer’s disease.

What is the cause of Aria?

Amyloid-related imaging abnormalities (ARIA) have been reported in Alzheimer’s disease (AD) patients treated with bapineuzumab, a humanized monoclonal antibody to amyloid-β. ARIA includes MRI signal abnormalities suggestive of vasogenic edema and sulcal effusions (ARIA-E) and hemosiderin deposits (ARIA-H).

Who makes Lecanemab?

Eisai and Biogen are collaborating on the joint development and commercialization of AD treatments. Eisai serves as the lead in the co-development of lecanemab and Biogen serves as the lead in the co-development of aducanumab, an anti-Aβ antibody.

What is PACC5?

PACC5 includes CAT, LMDR, DSC, MMSE, and FCSRT96. Abbreviations: CAT, category fluency; DSC, Digit-Symbol Coding Test; FCSRT96, Free and Cued Selective Reminding Test; LMDR, Logical Memory Delayed Recall; MMSE, Mini–Mental State Examination.

What kind of disease is solanezumab used for?

Solanezumab. Solanezumab is a monoclonal antibody being developed by Lilly as a potential therapy for people with mild cognitive impairment caused by Alzheimer’s disease (AD), preclinical AD, and dominantly inherited AD.

When did solanezumab go into Phase 3 trials?

Solanezumab has gone through a large development program that began in Phase I in 2004 and Phase III trials were completed and results announced in September 2012. Solanezumab is a monoclonal antibody that selectively binds to soluble Aβ to promote Aβ clearance.

When was solanezumab filed for patent in the US?

It is covered under the patent US 7,195,761 B2, which was filed in 2002 by Eli Lilly, Indianapolis, IN, and Washington University, St. Louis, MO. In 2011, TPG-Axon Capital funded part of the phase 3 trials. It will receive an estimated $70 million of based on sales milestones after the launch of the product.

How does solanezumab work in the cerebrospinal fluid?

Solanezumab binds free amyloid beta which causes amyloid beta42 to solubilize to reestablish the equilibrium in the cerebrospinal fluid. Solanezumab is expressed in Chinese Hamster Ovary cells. The produced antibodies are extracted and purified according to the standard procedures of the art.

Are there any clinical trials of solanezumab yet?

One study ( NCT01953601) is focusing on people with mild memory impairment, while another ( NCT01739348) has enrolled patients with mild to moderate Alzheimer’s disease. So, the final word on the amyloid theory’s validity is not yet out — and will likely not be determined until more trials have concluded.

Which is monoclonal antibody does solanezumab work against?

Solanezumab is a monoclonal antibody against Aβ and, like flecanide, may also remove Aβ. Lilly was not alone in its attempt to target Aβ. Bapinezumab, funded by Pfizer and by Johnson & Johnson, failed in Phase III trials. From: Foods and Dietary Supplements in the Prevention and Treatment of Disease in Older Adults, 2015

When did Eli Lilly start solanezumab Phase 3 trial?

Prespecified analysis of a subgroup of patients with mild cognitive impairment within phase 3 trials showed significant stabilization of cognition, which prompted Eli Lilly to conduct a third phase 3 trial that started in 2013 to further confirm whether solanezumab is able to slow cognitive and functional decline in patients with mild AD.

Are there any immunotherapy that recognizes soluble Aβ?

Another anti-Aβ immunotherapy treatment currently being tested in clinical trials is solanezumab. This antibody, developed by Eli Lilly, is an mAb that recognizes a linear epitope in the middomain of the Aβ peptide and recognizes only soluble Aβ.