Blood Test for Amyloid in BAN2401 AD Prevention trial

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NF52
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Blood Test for Amyloid in BAN2401 AD Prevention trial

Post by NF52 »

Some encouraging news on blood tests that can accurately predict whether someone has amyloid in their brain (not yet at CVS, folks!) [See my disclosure at end of post]

New Blood Test To Identify People At Risk Of Developing Alzheimer's Symptoms Will Be Used In Clinical Trial Aiming To Prevent Memory Loss

For those of you who might be interested in this study, here's an excerpt from the news release link above:
"Blood-based screening is a giant leap forward in detecting changes in the brain among people who do not yet show memory loss symptoms," said Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women's Hospital, Harvard Medical School and co-principal investigator for the AHEAD Study. "New blood test technology can help identify those more likely to have Alzheimer's disease changes in their brains, which enables them to enroll in prevention or treatment trials as early as possible. This is a remarkable achievement that may lead to detecting and treating Alzheimer's much earlier, and hopefully one day, preventing the memory loss associated with this devastating disease."

Funded by the National Institutes of Health (NIH) and Eisai Inc., a U.S. subsidiary of Eisai Co., Ltd., the AHEAD Study is enrolling people between the ages of 55 and 80 to test whether removing amyloid plaques in the brain can delay or prevent the onset of Alzheimer's symptoms. The study will enroll 1,165 participants from North America, with research centers in 75 U.S. and Canadian communities. Researchers believe their use of a screening blood test will lower barriers to participating in clinical trials, especially among communities of color, which are historically underrepresented in Alzheimer's trials.
Study locations and eligibility requirements can be found at AHEAD Study
FYI: All clinical trials involve a visit for explanation of the trial and discussion of a lengthy consent form usually with a brief cognitive test. The next step, considered the first Screening visit, can last 3-5 hours and includes cognitive tests, blood tests, health history and medications list, a brief neurological or physical exam and an EKG, and participant and study partner questionnaires. All that is used to see if you meet the health and cognitive requirements, BEFORE scheduling an Amyloid PET scan, MRI and possibly tau PET scan.

Using a blood test FIRST to find those most likely to be amyloid positive on a PET scan reduces the time burden on the 75% or so of people who typically don't have amyloid beta if cognitively unimpaired and promotes access in rural, diverse and under-served communities. More diversity in participants means more knowledge of the factors that affect responses to drugs in different groups, at different ages, genders and stages of prevention.

At the 2021 CTAD conference last week, Dr. Reisa Sperling showed a chart of those screened so far for the AHEAD studies by ApoE status (ApoE 2/2, 2/3, 2/4, 3/3, 3/4, 4/4). The total of 304 ApoE4 carriers were almost perfectly divided between amyloid positive (153) and amyloid negative (151). BUT ApoE4 carriers were only 46.1% of all those screened, yet were 77% of the amyloid positive group!. Those most likely to have amyloid beta were above the age of 65.

[Full disclosure: I am an unpaid member of the Research Participant Advisory Board at the Alzheimer's Clinical Trial Consortium, an NIH-funded effort to improve AD clinical trials. The AHEAD studies of BAN2401 (lecanemab) are one of the public/private partnerships coordinated by ACTC. The Advisory Board's role is to "Provide guidance on study design including the following areas: ethical considerations, disclosure of personal and study research results, privacy, recruitment approaches that engage diverse communities and increase trial generalizability, burden for participants and study partners, and selection of therapeutics, balancing risk and potential benefit..." In other words, I'm glad to help anyone interested in info on clinical trials, but not on commission to find folks! ]
4/4 and still an optimist!
antimatter37
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Re: Blood Test for Amyloid in BAN2401 AD Prevention trial

Post by antimatter37 »

Thanks NF52 for this report. There is another trial, "Trailblazer-ALZ" that is also looking at using a monoclonal antibody as a preventative therapy for persons at high risk for Alzheimer's. The Trailblazer trial uses a Lilly drug called donanemab while the trial you refer to uses a drug called lecanemab. Here is a short explanation of these two drugs from Clinicaltrialsarena.com:

"Both drug candidates are intravenously administered mAbs that aim to reduce the formation of amyloid plaques in the brain of AD patients. Lecanemab targets soluble Aβ monomers while donanemab binds to a modified form of Aβ, N3pG, that is localized in amyloid plaques. Reduction of these toxic proteins is hypothesized to be of significant clinical value in AD and treating the disease in the early stages, and consequently slowing clinical decline."

I have looked at both trials myself (66 years old, APOE 4/4, cognitively normal). Both trials have clinics in the city where I live. The lecanemab trial is not yet recruiting at the clinic in my hometown, while the donanemab trial is. I called the clinic for the donanemab trial, and they agreed to see me. I passed a short cognitive test over the phone before the office visit. The primary purpose of the office visit is to draw blood to test for phosphorylated tau, or p-tau. The trial will use only those folks who are cognitively normal but test positive for p-tau. The blood results take 3-4 weeks, so I do not yet know where I stand as far as the trial goes.

It is interesting that the donanemab trial looks for p-tau while the lecanemab trial looks for Amyloid in the blood. If you are one that follows Dr. Rudolf Tanzi, the presence of p-Tau seems to be the more ominous of the two if found in the bloodstream. For those interested in these trials, you can look at clinicaltrials.gov in the U.S., and search for either LY3002813 (Trialblazer) or AHEAD 3-45 (Ahead).
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Re: Blood Test for Amyloid in BAN2401 AD Prevention trial

Post by NF52 »

antimatter37 wrote:Thanks NF52 for this report. There is another trial, "Trailblazer-ALZ" that is also looking at using a monoclonal antibody as a preventative therapy for persons at high risk for Alzheimer's. The Trailblazer trial uses a Lilly drug called donanemab while the trial you refer to uses a drug called lecanemab. Here is a short explanation of these two drugs from Clinicaltrialsarena.com:

"Both drug candidates are intravenously administered mAbs that aim to reduce the formation of amyloid plaques in the brain of AD patients. Lecanemab targets soluble Aβ monomers while donanemab binds to a modified form of Aβ, N3pG, that is localized in amyloid plaques. Reduction of these toxic proteins is hypothesized to be of significant clinical value in AD and treating the disease in the early stages, and consequently slowing clinical decline."

I have looked at both trials myself (66 years old, APOE 4/4, cognitively normal). Both trials have clinics in the city where I live. The lecanemab trial is not yet recruiting at the clinic in my hometown, while the donanemab trial is. I called the clinic for the donanemab trial, and they agreed to see me. I passed a short cognitive test over the phone before the office visit. The primary purpose of the office visit is to draw blood to test for phosphorylated tau, or p-tau. The trial will use only those folks who are cognitively normal but test positive for p-tau. The blood results take 3-4 weeks, so I do not yet know where I stand as far as the trial goes.

It is interesting that the donanemab trial looks for p-tau while the lecanemab trial looks for Amyloid in the blood. If you are one that follows Dr. Rudolf Tanzi, the presence of p-Tau seems to be the more ominous of the two if found in the bloodstream. For those interested in these trials, you can look at clinicaltrials.gov in the U.S., and search for either LY3002813 (Trialblazer) or AHEAD 3-45 (Ahead).
Thanks for this update! Donanemab is a VERY interesting drug and the Trailblazer-ALZ3 trial is doing several new methods to reach people, including having fewer cognitive tests (every 6 months, not 3 months), most tests done at home on computers or tablets, care partners able to participate remotely also, so they don't miss work or have to spend time waiting in a site, and sites that are in community health settings, including many in underserved communities, to build trust and make it easier for people to participate. I think they will also have infusion (IV) options at homes or in the community settings, to be easier for people who live in less populated areas.

AHEAD trials are also getting tau PET scans on people, although unlike donanemab they are not requiring a positive tau test for enrollment. The early evidence from both BAN2401 and Donanemab is that they reduce amyloid by a huge amount in 18-14 months (80% or more, moving most people below the "amyloid positive" threshold. More surprisingly, they also reduce tau, although by not as much. Finding that removing amyloid may also prevent tau, which may be an important "ominous" actor in neuron death and cognitive impairment would make it far easier to make a case that a change in biomarker is predictive of at least a likely change in trajectory of decline. I suspect most trials will be using blood tests for tau within a year as well in screening, since they seem to all be using FDA guidance that allows for "adaptive" trials based on new data and techniques.

Great that you are ready to be in the vanguard of a very different type of AD trial: one in which the target group is clearly defined, the mechanism of action is not primarily against amyloid plaques but against amyloid oligomers and with careful monitoring. Being empowered by knowledge seems to me a good thing and helping to find answers to tough questions even better. Keep us posted if you're comfortable doing that!

NF52
4/4 and still an optimist!
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