Inside the Alzheimer's pipeline: diversity of treatments spells promise
A new report from the industry trade group PhRMA reveals that there are currently 92 medicines in development for the treatment of Alzheimer’s and other dementias. Lundbeck has three different compounds in our own pipeline that are being studied for use in Alzheimer’s patients, plus a variety of pre-clinical research projects. Across industry and academia, there is powerful momentum in Alzheimer’s research.
But it is not just the volume of research activity today that is exciting; it’s the diversity and breadth of treatments in development.
Alzheimer’s is an exceptionally complex disease with several underlying pathological processes. There will likely be no single silver bullet. Instead, successful treatment will most likely involve a combination of therapies—multiple medicines targeted at different aspects of the disease process. This is how we now treat and manage HIV and some cancers—turning them from fatal disease to manageable chronic disease using a combination of therapies.
The range of treatments cited in PhRMA’s new report demonstrates the noteworthy progress we are making in the fight against this formidable disease—progress that is leading us closer toward a combination therapy for Alzheimer’s. The promise I see in today’s pipeline is our increasing ability to target the disease in more precise ways with a wider arsenal of weapons.
The promise I see in today’s pipeline is our increasing ability to target the disease in more precise ways with a wider arsenal of weapons.
Changing the course of the disease
The majority of medicines in the Alzheimer’s pipeline target beta-amyloid plaques and tau protein tangles – the two most prominent features of the disease in the brain. Significantly, 75 percent of the medicines in Phase II or Phase III clinical testing are disease-modifying treatments, and the possibility that one or more of these investigational therapies could slow or stop the progression of the disease is incredibly exciting.
At Lundbeck, we are pursuing both anti-beta-amyloid and anti-tau disease-modifying approaches. We are investigating an anti-beta-amyloid active immunotherapy that—like a vaccine—could stimulate the body’s immune system to produce antibody to recognize beta amyloid as foreign and attack it. We’re also collaborating with scientists at NYU to study a therapeutic antibody that could potentially stop the spreading of the pathological tau protein.
Beyond the beta amyloid and tau medicines currently in clinical trials, researchers across the globe are working on a number of exciting pre-clinical research projects. The complexity of the disease requires that we evaluate a broad range of possible interventions in the disease process. For example, scientists are looking at the role neuroinflammation may play in Alzheimer’s. And researchers are exploring how checkpoint inhibitors, which have been wildly successful in oncology treatment, could be used in Alzheimer’s. As an example, in partnership with the Israeli biotech company ImmunoBrain Checkpoint, we’re exploring how checkpoint inhibitors might help the body to identify toxic proteins as foreign and fight them before they can accumulate and damage the brain.
Pursuing symptomatic relief
At Lundbeck, we think there is a need to pursue these kinds of disease-modifying treatments at the same time that we pursue symptomatic treatments. Because until there is a cure, people with Alzheimer’s and their caregivers will continue to seek relief from the vexing symptoms of the disease.
One of the trials counted in the report is the Phase III testing of a potential treatment for agitation in Alzheimer’s disease that we are investigating in partnership with Otsuka Pharmaceuticals. Agitation is one of the main reasons people must leave their homes and families and move into care facilities. Managing symptoms may help to keep people in their homes longer, which may ease stress and disease burden on patients, caregivers and entire families.
Cognitive decline is one of the more significant impacts of Alzheimer’s, and we are currently conducting a Phase I clinical trial for a study drug that is intended to be evaluated for symptomatic treatment of cognitive decline in Alzheimer’s and schizophrenia patients.
Building on advancements in biomarkers, we can now better qualify patients for trials based on biological changes of the disease.
Optimism despite setbacks
There is so much happening in Alzheimer’s research today and the learnings are coming at rapid pace. That said, it’s hard to ignore the Alzheimer’s clinical trial failure rate. As noted in the PhRMA analysis, just four new Alzheimer’s medicines were approved between 1998 and 2017, with another 146 unsuccessful attempts. That is a dismal 2.7 percent ratio of success in bringing treatments to patients.
But as the new report explains, each of these failed trials is contributing to our understanding of the disease. Building on the learnings of past trials and advancements in biomarkers, we can now better qualify patients for trials based on biological changes of the disease, rather than relying solely on a clinical assessment of symptoms. And that means we can target therapies to specific stages of the disease and underlying pathology with much greater precision. And that will hopefully lead to more successful trials.
I am truly confident that we are on the cusp of significant breakthroughs, and I am excited to be a part of this moment.
