{"id":363386,"date":"2023-11-30T04:00:00","date_gmt":"2023-11-30T09:00:00","guid":{"rendered":"https:\/\/platohealth.ai\/could-an-alzheimers-vaccine-make-treatment-more-affordable\/"},"modified":"2023-11-30T06:30:14","modified_gmt":"2023-11-30T11:30:14","slug":"could-an-alzheimers-vaccine-make-treatment-more-affordable","status":"publish","type":"post","link":"https:\/\/platohealth.ai\/could-an-alzheimers-vaccine-make-treatment-more-affordable\/","title":{"rendered":"Could an Alzheimer\u2019s vaccine make treatment more affordable?","gt_translate_keys":[{"key":"rendered","format":"text"}]},"content":{"rendered":"
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Alzheimer\u2019s research has come a long way since the disease was first identified more than a century ago. Now, as treatments have been developed to reduce the harmful proteins in the brain that are associated with Alzheimer\u2019s, vaccine trials are underway to eliminate these proteins. But how far along are these vaccines in the clinic?<\/strong><\/p>\n

One of the awaited Alzheimer\u2019s vaccines is American company Vaxxinity\u2019s UB-311. Found to be well tolerated in the clinic, the candidate targets toxic forms of aggregated amyloid beta in the brain, a hallmark of the disease.<\/p>\n

Vaxxinity\u2019s Alzheimer\u2019s vaccine in phase 2 trials<\/h2>\n

UB-311 is a synthetic, peptide-based active immunotherapy that is based on the biotech\u2019s Vaxxine Platform. The platform aims to combat chronic diseases by creating peptides that are designed to detect the presence of unfavorable molecules, and induce a target-specific antibody response to them.\u00a0<\/p>\n

These peptide vaccines are administered in smaller doses to elicit an immune response, as opposed to monoclonal antibodies \u2013 targeted drugs for certain chronic diseases \u2013 which are far more expensive too. Vaccines also last longer since they induce the body to create its own antibodies, unlike monoclonal antibodies, which are made in a lab and injected into the bloodstream.<\/p>\n

With the help of the platform, Vaxxinity\u2019s peptide activates T-helper cells, which in turn alerts B cells to generate antibodies against the B cell epitope. The peptide is connected to a linker, which attaches to the B cell epitope, optimizing the presentation of the target to the immune system. Since this is a targeted approach, the process fends off inflammation, which is typical when an immune response is triggered.\u00a0<\/p>\n

In a phase 2a trial<\/a> that involved 43 participants, the vaccine showed that it was safe and tolerable, plus, it prompted an immune response in nearly all the patients. Although the company had been looking to do a larger trial to further confirm the results through collaboration, the funding environment didn\u2019t seem to embrace the idea behind Alzheimer\u2019s vaccines for a few years, according to a Reuters report<\/a>. Until the U.S. Food and Drug Administration\u2019s (FDA\u2019s) approval of LEQEMBI<\/a>, a few months ago.<\/p>\n

LEQEMBI approval clears way for Alzheimer\u2019s vaccines<\/h2>\n

Owned by Japanese healthcare company Eisai and its American multinational partner Biogen, LEQEMBI, which works by reducing amyloid plaques to slow disease progression, sparked interest among investors, which has led to more funding for Alzheimer\u2019s research<\/a>. While the breakthrough drug is the first one to slow cognitive decline in patients with early-stage Alzheimer\u2019s disease, the $26,500-per year price tag attached to it, poses a barrier to gaining access to it in the first place.<\/p>\n

Moreover, drugs like Leqembi have to be administered every two weeks, whereas a vaccine would be given a few times a year, potentially cracking the affordability barrier for millions.<\/p>\n

\u201cImagine expanding the addressable patient population of beta-amyloid immunotherapies by multiple orders of magnitude, potentially over 1,000x, and delivering life-changing medicine at a fraction of the cost. That is our vision for UB-311, and the potential power of active immunotherapies,\u201d said Mei Mei Hu, chief executive officer (CEO) of Vaxxinity, in a press release<\/a>.<\/p>\n

And it\u2019s not just Vaxxinity that is in the running to potentially slash these prices. Spanish company and Grifols subsidiary Araclon Biotech, is developing a vaccine that is designed to target the C-terminal end of amyloid beta 40 (\u0391\u03b240). This can improve the safety profile of the vaccine candidate ABvac40 as antibodies can only bind to it when the peptide is separated from the cell membrane, to prevent harmful reactions.<\/p>\n

The candidate slowed disease progression up to 38% compared with placebo in a phase 2 trial, although it wasn\u2019t a study meant to assess its efficacy. There were also no instances of swelling, although some cases of micro-hemorrhages were reported \u2013 none that led to its discontinuation \u2013 which have been of concern in the past.<\/p>\n

For instance, Elan Pharmaceuticals had pulled the plug on its candidate owing to patients experiencing meningoencephalitis, a life-threatening condition that causes inflammation in the brain.<\/p>\n

In fact, the first ever vaccine candidate for Alzheimer\u2019s was abandoned more than two decades ago, when 6% of the patients in the trial experienced brain inflammation caused by meningoencephalitis. This was because of an inflammatory T-cell response generated by the candidate AN1792. Although A\u03b2 levels and plaque counts were lowered during treatment, the adverse side effects posed a significant threat to patients.<\/p>\n

With nobody to pick up the pieces of the failed trial at the time, monoclonal antibodies then stole the limelight. A research paper<\/a> published in the National Library of Medicine, suggested that the reason why a vaccine for the neurodegenerative condition was struggling to get past clinical trials<\/a>, was because they either set off excessive immune reactions or the adjuvant-free vaccine therapies which tried to step around the side effects, simply weren\u2019t effective enough.<\/p>\n

AC Immune candidate offers hope to Down\u2019s syndrome community<\/h2>\n

So now, this renewed interest in vaccines to treat or prevent Alzheimer\u2019s disease, seems to pivot towards creating a safety profile. Yet, like with most Alzheimer\u2019s research, the Down\u2019s syndrome community isn\u2019t included in trials.\u00a0<\/p>\n

Down\u2019s syndrome or trisomy 21, is a genetic disorder caused by the presence of three copies of the 21st chromosome. People with Down\u2019s syndrome have an increased risk of developing Alzheimer\u2019s disease, often at a young age. As 90% of people with Down\u2019s syndrome will develop Alzheimer\u2019s, they make up the largest population of genetically determined Alzheimer\u2019s disease in the world. While some researchers have said that it is \u201cchallenging\u201d to find people to take part in trials, according to a Reuters report<\/a>, AC Immune is challenging this rhetoric.<\/p>\n

The Swiss company\u2019s phase 1\/2 ABATE trial is testing its Alzheimer\u2019s vaccine candidate ACI-24.060 in patients with Down\u2019s syndrome. The candidate is designed to generate antibodies that target misfolded \u0391\u03b2 to prevent its accumulation and clear out amyloid plaques. Preclinical studies have shown that the candidate could induce a broad immune response, but to find out how the ongoing trial pans out, we will have to wait until next year.<\/p>\n

More Alzheimer\u2019s vaccine trials in progress<\/h2>\n

Meanwhile, there are various trials underway for Alzheimer\u2019s vaccine. Having discovered the \u201cAchilles heel of the tau protein,\u201d AXON Neuroscience, based in Slovakia, is developing a vaccine that will train the immune system to attack it<\/a>. Like amyloid beta, tau protein is another protein that is linked to cognitive decline in Alzheimer\u2019s, and Axon has located the region where tau proteins interact with each other to form aggregates.\u00a0<\/p>\n

Its vaccine immunotherapy AADvac1 underwent a phase 2 trial<\/a>, a few years ago. This first-in-human tau vaccine was found to be safe, while having induced a robust antibody response in patients with mild Alzheimer\u2019s. However, the company has yet to begin a phase 3 study for the candidate.\u00a0<\/p>\n

Furthermore, just yesterday, Swedish company Alzinova announced<\/a> encouraging phase 1b results for its vaccine candidate ALZ-101. The vaccine, which is designed to stimulate the production of antibodies against toxic A\u03b2, met its primary endpoint of safety and tolerability after 20 weeks. While no cases of amyloid-related imaging abnormalities (ARIA) were identified with regards to brain swelling (ARIA-E), one case of microbleeding (ARIA-H) was noted. The patient, who had entered the study with a history of ARIA-H, was observed to have had a symptom-free increase in size.\u00a0<\/p>\n

As the trial has met its endpoints, it will begin an extension of the study, which will evaluate ALZ-101\u2019s long-term safety, tolerability and immune response, as well as further data on how the vaccine affects cognitive function.<\/p>\n

As researchers race to develop vaccines that eliminate adverse side effects like hemorrhaging and cut treatment costs, this offers hope for patients with Alzheimer\u2019s disease. And since this revived interest in Alzheimer\u2019s vaccines has been anchored by Vaxxinity\u2019s and AC Immune\u2019s candidates, among others so far, clinical trials for these vaccines might be ones to look out for in the next few years.<\/p>\n<\/div>\n

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