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Announcements

Statement on discontinuation of BACE 1 inhibitor CNP520 in the Alzheimer's Prevention Initiative Generation Study 1

NIA Office of Communications & Public Liaison, 301-496-1752, nianews3@mail.nih.gov

Like our trial partners, we too are profoundly disappointed about the news of the need to discontinue the BACE 1 Inhibitor CNP520 arm of the Alzheimer’s Prevention Initiative (API) Generation Study 1. We understand that this will be disheartening to the study participants and investigators; however, the safety of participants is the primary concern leading to this decision. We are grateful to the participants and their study partners for their time and valuable contributions to this research.

The Generations Study 1 was designed to test the safety and effects of CNP520, a BACE 1 inhibitor, and CAD106, an immunotherapy, in cognitively normal older adults who are at risk of developing dementia based on their age, genetic status, and brain amyloid levels. Given the assessment showing a worsening of cognitive function in the CNP520 arm, the decision was made to discontinue treatment. The CAD106 treatment arm will continue. We will wait for the data to undergo further analysis and for study investigators to share a clearer picture of the results, before determining what implications this finding will have going forward. Once the data are available and analyzed, we will know more about the effects of this BACE 1 inhibitor and will apply this information to all relevant studies in the future.

We appreciate the commitment that has been made to share the data broadly, providing the research community with a better understanding of this disease and treatment targets, even when the results are disappointing. The preliminary information from this trial will shape our future efforts. For example, all safety information will be considered before moving forward on trials testing similar treatments, an essential practice that we always pursue.

It is also important to note that BACE 1 inhibitors are a potential treatment because they prohibit the production of amyloid-beta, the plaques that are one of the hallmarks of Alzheimer’s disease. Other treatments targeting amyloid work by different mechanisms of action and still warrant investigation. For example, a class of immunotherapies focus on providing antibodies that target the elimination of amyloid-beta.

Importantly, as a result of recent advances in understanding the pathology of Alzheimer’s disease, multiple therapeutic interventions are now being studied that target aspects of the disease beyond amyloid and tau.

Despite this setback, we remain at a point in Alzheimer’s disease research where we know more about potential targets than ever before, as the result of advances in genetics, the analysis of vast datasets in projects such as the Accelerating Medicine Partnership (AMP) for Alzheimer’s Disease, the AD neurotherapeutics program, and other areas of research that have emerged over the last several years.

Richard J. Hodes, M.D.
Director, National Institute on Aging, NIH

Funding for the API Generations Study 1 was provided in part by NIA grant UF1AG046150, Novartis, and Amgen.