Photo: MRI brain scan background, magnetic with blue tones/iStock, DedMityay
After decades of setbacks and failures, the Alzheimer’s disease market is poised to offer two disease-modifying treatments. Biogen and Eisai’s Requembi received full approval last July, and FDA approval for Eli Lilly’s donamab is an immediate approval after the company recommended that a decision be expected by the end of 2023. There is a possibility that
The anti-amyloid field got off to a rocky start after Aduhelm won history-making but controversial approval in 2021. Biogen has since decided to stop marketing the embattled therapy and end post-approval studies. Several other companies are currently seeking to bring investigational drugs to market.
“Alzheimer’s disease treatment is still in its early stages,” said Greig Svannabej, senior biopharmaceutical and biotech equity research analyst at Mizuho Americas. Many of the candidates currently in development target specific parts of the Alzheimer’s disease puzzle, such as trigger receptors expressed on the myeloid cell 2 (TREM2) and hepatocyte growth factor (HGF) systems. Ms. Swannavage said. biospace He said he believes combination approaches, like those seen in cancer treatment, are where the field is ultimately headed.
Here are five Alzheimer’s assets and data readouts that Suvannavejh expects to see in 2024.
1. Alector/AbbVie AL002
Alector Therapeutics’ monoclonal antibody AL002 contains a novel target, TREM2. Dysfunction of this receptor is thought to cause Alzheimer’s disease and other dementias, according to the company’s website. AL002 activates TREM2 signaling and improves cell survival and activity.
The injected antibodies are currently in Phase II trials, with data readouts that will determine the future of the program expected in the fourth quarter of 2024, Suvannavej said. AbbVie has full opt-in rights to Phase III development if the results are sufficiently convincing.
2. Phosgonimethone from Athira Pharma
According to Attila, this potential first-in-class therapy is designed to modulate the HGF system to activate neuroprotective and anti-inflammatory pathways in the central nervous system. In December, Phosgonimeton failed in a Phase II trial in Parkinson’s disease dementia, or dementia with Lewy bodies. However, when Athira reduced the modified intent-to-treat population to her five patients, she saw statistically significant improvements in cognitive scores.
Athira has now completed enrollment in a Phase II/III trial in mild-to-moderate Alzheimer’s disease, with topline data expected to be released later this year. Suvarnavej said he finds phosgonimeton “interesting” despite controversial data collected so far, suggesting HGF may improve neuronal function and anti-amyloid therapy. He added that it is a unique drug target that could potentially be used in combination with anti-tau therapies.
3. Algeon ALZ-801
The first oral disease-modifying treatment for Alzheimer’s disease could emerge from Framingham, Massachusetts-based Alzion’s lab. ALZ-801 is designed to prevent the formation of amyloid oligomers, the toxic amyloid species that ultimately form plaques. At least he has been tested on patients with one copy. APOE4 These people tend to accumulate more amyloid beta in their brains, which could be due to a genetic mutation. Topline results from the ongoing Phase II trial show that after two years, ALZ-801 preserved the hippocampus without increasing the risk of ARIA, a side effect sometimes seen with anti-amyloid therapies such as Rekenbi and Donamab. Indicated.
ALZ-801 is currently in Phase III trials, with results expected to be announced around the middle of this year, Suvannavej said. Algeon is currently privately held, but Suvannavej believes a positive reading of the data could lead to a deal with a larger company or even an IPO.
4. Prothena PRX012
Protena’s next-generation anti-amyloid antibody, which has received FDA Fast Track designation, has the potential to be best-in-class, Suvannavej said. PRX012’s key differentiator is that it is administered subcutaneously, as opposed to intravenously like Rekenbi and donanemab.
Although the candidate is still in Phase I trials, investor interest was evident last year, resulting in a rise in stock prices due to the convenient formulation, efficacy and potential to avoid ARIA, Suvannavej said. Ta. However, Suvannavej noted that delays in publishing clinical results have dampened some of the excitement. Prothena reported in a January press release that its ongoing Phase 1 clinical trial is “continuing as planned” and that an update is expected later this year.
5. Axum Therapeutics AXS-05
Unlike the other drugs on this list, this drug candidate is a symptom-treating therapy rather than a disease-modifying therapy. Axum is repurposing a currently marketed drug as an antidepressant and testing it against the agitation associated with Alzheimer’s disease. Agitation is reported in about 70% of Alzheimer’s patients and is associated with functional decline, early nursing home placement, and increased mortality, according to Axsum’s website.
Already on track with positive Phase II and III data, Axum’s second pivotal Phase III trial is expected to be announced in the second quarter of 2024, Suvannavej said. Stated. Last year, Otsuka and Lundbeck won approval for Rexulti for Alzheimer’s disease agitation, but the drug comes with a black box warning for older patients with dementia-related psychosis. Suvannavejh said that if Axsome is successful, it will be the only drug on the market that is indicated for Alzheimer’s disease agitation without such warnings.
As of January 2023, there are 187 trials evaluating 141 drugs for Alzheimer’s disease. With these results, and more he expects in 2024, an attractive option for Alzheimer’s patients is poised to be added.
“In my opinion, this is a very exciting place for innovation and Alzheimer’s disease,” Suvarnavej said.
Kate Goodwin is a freelance life sciences writer based in Des Moines, Iowa. Contact her at kate.goodwin@biospace.com and on LinkedIn.
