I recently returned from San Diego and from the Alzheimer’s Association International Conference (AAIC). AAIC represents the best combination of scientific research, community contributions, and collaboration that are essential to making progress against this devastating disease. It was great to see friends, colleagues, community members, and researchers I’ve long admired share what I’ve learned from the Alzheimer’s cohort research programs.
Through my talks and scientific presentations at the meeting, I was struck by the scale, the excitement – and if I’m honest – the tense anticipation we all feel at this pivotal time in Alzheimer’s research. As we look forward to a number of results from the much-anticipated phase III amyloid antibody clinical trials in the coming months, this is the perfect time to reflect on how much we’ve learned about the disease and how our ongoing work, research, and even setbacks, have built the foundation of the field today.
The delicate and important task of interpreting and translating lessons learned from the findings of previous research programs has advanced our understanding, and even our definition of, Alzheimer’s disease. We listened closely to clinicians and people with Alzheimer’s disease as well as their loved ones and patient advocacy groups–and most importantly, we carefully incorporated insights from clinical setbacks, which are reflected in the way we design and run our clinical trials. How our medicines are dosed and the ways we work to provide support other than our medicines. We hope that by using this knowledge and a purposeful approach, we get closer to being able to answer important scientific questions that translate into meaningful learning in the field – with our ultimate goal of making a positive impact for people living with Alzheimer’s disease. illness.
For us at Genentech and Roche, our approach to Alzheimer’s is driven by our commitment to transforming how the disease is detected, diagnosed and treated. Over the course of more than two decades of dedication to Alzheimer’s disease, we have made contributions to the field–from leading the understanding of the biology and pathophysiology of the disease, to advancing the identification and application of biomarkers in neuroscience research, and to improving study group selection and optimization. Clinical trial design. There was a lot to learn and designing studies that could capture slowing cognitive decline and functional decline, takes time. The more we learn about the pathophysiology of Alzheimer’s disease, the more convinced I am that making a significant clinical impact and demonstrating meaningful change will require intervention with the appropriate therapeutic agent in the appropriate patient group at the optimal time in the course of the disease.
For more than a decade, we did not have the technology or confirmatory testing capabilities needed as part of our standard clinical trial inclusion criteria. The introduction of positron emission tomography (PET) was a critical step in ensuring that clinical trials evaluated people with positive beta-amyloid. As an area, we are now looking to expand beyond PET to include more accessible detection methods, such as cerebrospinal fluid (CSF) and blood-based biomarkers (BBBM), to help democratize the ability to diagnose people across geographic regions and socioeconomic status.
As science developed, Genentech and Roche were the first to use amyloid fluid biomarkers as an option in our Alzheimer’s disease clinical program, providing flexibility while ensuring appropriate patient assessment. Furthermore, Roche Diagnostics is developing a comprehensive biomarker platform to help detect amyloid pathology in the early stages of Alzheimer’s disease. This includes a CSF test with a high compatibility of amyloid PET as well as a minimally invasive blood test, which has the potential to select patients who need additional confirmatory procedures. Once available and used in clinical practice, CSF and blood biomarker tests will allow timely and accessible assessment of patients suspected of having Alzheimer’s disease.
But the “right patient” goes far beyond confirmed pathology. At Genentech, we are committed to developing comprehensive research and addressing barriers to ensure that future safety and efficacy data are more reflective of the population at large. We plan our studies in collaboration with the Alzheimer’s disease community to better meet the needs of people with the disease, now and in the future. We are leading advances in areas beyond clinical research and partnering to forge new collaborations to collectively address health disparities to ensure that more people have access to the appropriate diagnoses, treatment, and care for Alzheimer’s disease.
the right time
The concept of time in Alzheimer’s disease is very different from the way we understand and look at other progressive diseases, such as cancer. While the development of cancer is often measured in months or years from the time symptoms appear until diagnosis, the impact of Alzheimer’s disease on the brain is measured over decades. Changes in the brain, such as the accumulation of beta-amyloid and tau, begin to form 10-20 years before significant cognitive, functional, or behavioral symptoms appear. Furthermore, Alzheimer’s disease may be driven and spread by different mediators (eg, beta-amyloid, tau) at different stages of the disease course. This idea is supported by the rapidly developing understanding of fluid biomarkers for Alzheimer’s disease and its subtypes over the past decade, which I believe shows great promise for developing a more personalized approach to treating Alzheimer’s disease in the future.
The majority of neurodegenerative disease research indicates that intervention in the early stages of neurological disorders such as Alzheimer’s offers the greatest opportunity to slow or halt the progression of cognitive and functional decline in patients. This year we launched a secondary prevention study called SKYLINE to test this hypothesis. The study will evaluate the potential to slow the onset and progression of Alzheimer’s disease to relieve symptoms in cognitively unaffected people with early biomarkers of the disease.
Unfortunately, despite the tremendous amount of effort, time, and resources invested in Alzheimer’s disease research, there is still no fully approved treatment to slow or halt the progression of the disease – also known as disease-modifying therapy. In just the last two decades, clinical trials evaluating more than 200 molecules in the treatment of Alzheimer’s disease have been started and stopped.
While on the surface these numbers may seem discouraging, with every drug and every trial we have conveyed insights to improve future programs, I am confident that upcoming scientific and therapeutic milestones will improve our understanding of the disease and how we deal with society’s presentation of Alzheimer’s disease.
At Genentech, your approach has always been to follow the science and explore multiple therapeutic approaches that address the major pathways of Alzheimer’s disease, including beta-amyloid and tau. Fortunately, science never stops and there are a number of emerging and evolving areas of therapeutic research. Important questions about potential therapeutic interventions targeting beta-amyloid, tau and other targets are still being explored. Ultimately, it would likely require a multi-targeted approach to completely halt disease in its tracks, ideally targeting specific pathophysiological drivers at appropriate times in the disease course.
Where do we go from here
We believe that in order to successfully address the profound need for Alzheimer’s disease, we must balance rigorous, informed and cutting-edge science with comprehensive and comprehensive support for those diagnosed, their families and affected care partners as well. We have to think bigger and bolder – and we are.
We must follow the science as we seek to uncover points of contact across neurological disorders that may open crucial clues to slowing, stopping, and one day reversing neurodegeneration and its associated irreversible disability. Relevant biomarkers of neurodegeneration across neurodegenerative disorders – such as amyloid light chain, tau and neurofilaments – may provide the ability not only to elucidate the pathophysiology of complex neurodegenerative diseases, but also to standardize approaches to measuring disease progression and better assessing the potential for new treatments. We are also exploring research on the blood-brain barrier, potential routes through which it travels and the important role it plays.
We are committed to doing the right thing – through our science, our approach, and our actions. It is as if we are standing shoulder to shoulder with the Alzheimer’s community on the cusp of a new era in Alzheimer’s disease research. I hope this scientific moment in history will create momentum for advances in the treatment of Alzheimer’s disease and neurodegenerative disorders on a large scale.