Tag Archives: APOE4 trial

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Banner Alzheimer’s Institute gets $10M in new funding

The Alzheimer’s Association, GHR Foundation and Fidelity Biosciences Research Initiative announced $10 million in new research funding to Banner Alzheimer’s Institute (BAI), Phoenix, Arizona, to support a groundbreaking Alzheimer’s disease prevention trial that will launch later this year.

The funding, to be paid over five years as part of a broad public/private partnership, supports and extends the Alzheimer’s Prevention Initiative (API) APOE4 trial. The study is focused on determining whether therapies targeting amyloid proteins in the brain may prevent or delay the emergence of Alzheimer’s symptoms in people at particularly high genetic risk for developing the disease at older ages.

The new funding will support three aspects of the API APOE4 trial that otherwise would not be possible: (1) brain PET imaging at the start of the trial and two-year follow-up in 125 participants each year, (2) a sub-study to evaluate two remote genetic counseling approaches, and (3) expansion of the Alzheimer’s Prevention Registry for the APOE4 trial.

“The goal is to accelerate the global effort to eliminate Alzheimer’s disease,” said Maria Carrillo, Ph.D., Alzheimer’s Association Chief Science Officer. “Through efforts such as API, the Alzheimer’s Association envisions a time when we will have effective treatments to slow or stop Alzheimer’s in its tracks; plus preventive strategies and gold-standard care for all people affected by Alzheimer’s.”

The Alzheimer’s Association led the effort to bring the three funding organizations together. The award to API includes a $5 million lead gift from the GHR Foundation, a private family foundation.

API is led by BAI’s executive director, Eric Reiman, M.D., its director, Pierre Tariot, M.D., and one of its principal scientists, Jessica Langbaum, Ph.D.

“We are extremely grateful to these three organizations for their extraordinary support,” said Dr. Reiman. “These funds will not only help make it possible to evaluate two promising Alzheimer’s prevention therapies, but to do so in a way that will help the field find treatments that work as soon as possible.”

API was established to rapidly evaluate potential new treatments in people prior to developing clinical symptoms of Alzheimer’s who, based on their age and genetic background, are at highest risk of developing symptoms of the disease, including the API APOE4 trial and the Autosomal Dominant Alzheimer’s Disease Trial. That study is evaluating an investigational anti-amyloid therapy in 300 cognitively normal members of an extended family in Colombia, South America that includes carriers of a rare genetic mutation causing them to develop Alzheimer’s by about age 45. API is committed to sharing trial data and biological samples with the research community to help find better ways to test prevention therapies in the future, and to clarifying the role of APOE genetic testing and disclosure.

The API APOE4 trial is focused on how two investigational anti-amyloid therapies may prevent or delay the development of Alzheimer’s symptoms in a population known to be at high risk for the disease because of their age and genetic status. Specifically, participants in the trial must be age 60-75 and carry two copies of the APOE-e4 gene that greatly increases their risk for developing Alzheimer’s.

The trial will test two different potential therapies to see if one or both can prevent the development of memory and thinking symptoms of Alzheimer’s. The first treatment is an active immunotherapy aimed at triggering the body’s immune system to produce antibodies that block different forms of the amyloid protein, which many researchers believe plays a critical role in the development of Alzheimer’s. The second drug is designed to prevent the production of amyloid protein that accumulates in the brain to form plaques, one of the hallmarks of Alzheimer’s. The trial will involve about 1,300 research participants. Pending regulatory approval, the study is planned to begin in the late 2015/early 2016 in sites in North America and Europe, and last five years.

The new funding will support three aspects of the API APOE4 trial:

• Tau PET imaging, amyloid PET imaging, and FDG-PET imaging at baseline and two-year follow-up in 125 participants each year to determine if the two treatments change tau PET measurements and are associated with a therapeutic benefit. Tau protein helps maintain normal cell structure. In people with Alzheimer’s, tau in the brain becomes abnormal and forms tangles, one of the characteristic features of Alzheimer’s.

• The expansion of the Alzheimer’s Prevention Registry, which provides information about Alzheimer’s prevention research and is intended to support enrollment in the APOE4 trial and other prevention trials.

• Evaluation of two remote genetic counseling approaches using telephone versus real-time videoconference counseling. This will include measuring the psychological, behavioral and cognitive effects of APOE genotype disclosure in people who underwent both types of genetic counseling.

“Because participation in the API APOE4 trial requires knowledge of one’s genetic status, we need to determine how to best communicate the genetic risk for developing Alzheimer’s as well as how to counsel individuals on what this risk means,” said Dr. Tariot.

In September 2013, the U.S. National Institutes of Health (NIH) announced an initial commitment of $33.2 million in partial support for the API APOE4 trial. In July 2014, BAI announced a partnership with Novartis, which is providing its two investigational treatments and financial support. In its NIH grant applications, BAI committed to obtaining $15 million in philanthropic and in kind contributions. To support the API APOE4 trial, $5 million has been obtained through donations to the Banner Alzheimer’s Foundation. The $10 million award from the Alzheimer’s Association, GHR Foundation and Fidelity Biosciences Research Initiative completes Banner’s commitment for this trial.

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Banner Alzheimer’s Institute partners with Novartis

Jessica Langbaum, Ph.D.

Jessica Langbaum, Ph.D.

Researchers from the Banner Alzheimer’s Institute (BAI) today announced a partnership with Novartis in a pioneering medical trial to determine whether two investigational anti-amyloid drugs—an active immunotherapy and an oral medication—can prevent or delay the emergence of symptoms of Alzheimer’s in people at particularly high risk for developing the disease at older ages.

The five-year APOE4 trial will involve more than 1,300 cognitively healthy older adults, ages 60 to 75, at high risk of developing symptoms of Alzheimer’s because they inherited two copies of the apolipoprotein E (APOE4) gene—one from each parent. About 2 percent of the world’s population carries two copies of this gene and one in four people carry one copy of the APOE4 gene, which is strongly linked to late-onset Alzheimer’s.

The trial—subject to regulatory authority approval—will begin in 2015 at approximately 60 sites in Europe and North America, including BAI’s headquarters in Phoenix, Ariz. Participants will receive either the active immunotherapy or the oral medication or a placebo.

The study is partially funded by a $33.2 million grant commitment from the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services, awarded in 2013, and
more than $15 million in philanthropic and in-kind contributions by Banner Alzheimer’s Foundation. It is part of the Alzheimer’s Prevention Initiative (API), an international collaboration led by BAI to accelerate the evaluation of promising prevention therapies.

Today’s announcement of the partnership with Novartis, a Swiss pharmaceutical company, and the selection of the drugs to be studied, represent a dramatic investment in novel approaches to Alzheimer’s prevention research.

“We hope Novartis’s substantial investment of resources and expertise will lead to a significant breakthrough in Alzheimer’s research,” said Dr. Pierre N. Tariot, study director for BAI, an arm of Banner Health, one of the largest nonprofit healthcare systems in the United States. “We are taking clinical trials to a critical new stage. This approach shifts the research paradigm from trying to reverse disease damage to attacking and preventing its cause, years before symptoms could surface.”

The active immunotherapy is aimed at triggering the body’s immune system to produce antibodies that attack different forms of the amyloid protein, which many researchers have suggested plays a critical role in the development of Alzheimer’s. The oral medication is a BACE (beta-secretase1) inhibitor, designed to prevent the production of different forms of the amyloid protein.

The two drugs, which will be tested separately, are intended to stop the accumulation of amyloid in ways that differ from the anti-amyloid antibody therapies now being tested in API’s Autosomal Dominant Alzheimer’s Disease (ADAD) trial in Colombia, and in two other prevention trials. The drugs are being introduced even before amyloid accumulates in some of the participants’ brains. The trial will increase the chance of finding treatments that will prevent, slow or delay the loss of memory and other cognitive abilities associated with Alzheimer’s.

The new study marks the second major trial associated with API. In 2012, NIH announced the long-term ADAD study of cognitively healthy individuals who are destined to develop Alzheimer’s at an unusually early age because of their genetic history. The $100 million study—funded by NIH, BAI and Genentech, a biotechnology company—is focused on approximately 300 members of an extraordinarily large family from Colombia who share a rare genetic mutation that typically triggers Alzheimer’s symptoms around age 45.

The ADAD study, a partnership of BAI, Genentech and the University of Antioquia in Colombia, is evaluating the amyloid antibody agent crenezumab.

“There are no guarantees that any of these investigational treatments will prevent the clinical onset of Alzheimer’s disease,” said Dr. Eric M. Reiman, one of the study directors for BAI. “But we are grateful for these opportunities to find out.”

The APOE4 and ADAD trials will be critical in determining whether anti-amyloid treatments are likely to show benefit for Alzheimer’s. Both trials include the best-established cognitive and biological measures of the disease, and a strategy that might make it possible to substantially shorten the time needed to conduct future prevention trials. Both trials also include precedent-setting agreements for the sharing of study data and biological samples after the studies conclude.

Volunteers for the APOE4 study will receive either active immunotherapy injections or a BACE inhibitor in pill form or a placebo. Participants will be recruited via multiple venues, including the Alzheimer’s Prevention Registry website created by BAI in 2012. The registry (www.endALZnow.org) currently has more than 37,000 potential volunteers and is aiming to recruit more than 250,000.

The APOE4 study’s new website, which will launch in 2015, will create a platform to explain the study, register potential participants and provide disclosure information and consent forms. Volunteers who meet the study criteria will be asked to mail a sample of their genetic material (such as a cheek swab) to a laboratory. The volunteers will learn the results of that test in the context of possibly enrolling in the trial.

“This web research platform creates a powerful tool for any additional Alzheimer’s research,” said Jessica Langbaum, Ph.D., co-director of the study at BAI. “This infrastructure enables us to create more than just a single drug trial, but rather a template for testing a variety of treatments for many years to come.”

Volunteers who are selected will receive genetic counseling, as will others who are not chosen but who seek more information on their vulnerability. “We are keenly aware of the extreme sensitivity and emotional impact of disclosing genetic information,” Dr. Langbaum said. Volunteers accepted into the trial will already know they are at high risk, while others may learn of a lesser but still increased risk. For both of these groups, BAI will be providing more detailed information and genetic counseling in person, by phone or possibly through video-conferencing or telemedicine.

“We are excited about the chance to partner with Novartis, which has a longstanding commitment to the fight against Alzheimer’s and promising investigational treatments. They will conduct this study in a way that will be helpful to all stakeholders in the field,” said Dr. Tariot.

“We are now coming to believe that attacking Alzheimer’s disease, before clinical signs of memory loss and cognitive impairment become evident, may provide our best chance for effective therapies,” says Dr. Neil Buckholtz, Director of the Division of Neuroscience at the NIA. “These studies will be important in helping to determine if and how that can be done.”

Alzheimer’s is a debilitating and incurable disease that affects as many as 5 million Americans age 65 and older, according to a number of estimates. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to nearly triple by 2050.