Real progress in the fight against Alzheimer’s disease

R&D
fight against Alzheimer’s disease

These are encouraging times in Alzheimer’s disease research and treatment. After many setbacks, controversies, and scientific debates over several decades, we’ve recently seen the most significant breakthroughs in the history of this disease, and this is only the beginning.

According to the Alzheimer’s Association, 6.7 million Americans over age 65 suffer from Alzheimer’s disease and other dementias, a number that is expected to more than double by 2060 as our population ages.i It’s a cruel disease that robs patients of their memories and faculties. It’s fatal for patients and devastating for their families. It’s also a costly disease – costs in the form of lost time with loved ones, lost productivity, unpaid caregiving by family members and, of course, the direct cost of care, which is projected to reach nearly $1 trillion by 2050.

Aβ proteins - a telltale biomarker of Alzheimer’s disease

In 2021 – 115 years after the disease was first diagnosed – the US Food and Drug Administration (FDA) granted accelerated approval to a monoclonal antibody drug that removes amyloid-beta (Aβ) protein accumulation in the brain. These Aβ proteins are a telltale biomarker of Alzheimer’s disease. In January of 2023, the FDA provided accelerated approval to a second anti-Aβ monoclonal antibody, lecanemab, for the treatment of early Alzheimer's disease, further validating the treatment pathway.

A recently announced positive clinical study of a third anti-AB monoclonal antibody, donanemab, showed treatment significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer’s disease. These results and recent FDA approvals provide evidence that reduction of Aβ plaque is predictive of clinical benefit.

Taken together, these developments mark a watershed moment in Alzheimer’s disease research. Now that anti-Aβ is a viable clinically-sound treatment pathway, patients and physicians can do more than manage symptoms; they can directly treat the underlying pathology of the disease. These advances in treatment have been accompanied by rapidly evolving progress in Alzheimer’s disease biomarkers, which has enabled appropriate patient identification and shed light on further biological impact of these treatments.

But what’s next? What should we look forward to in the continued fight against this cruel and pernicious disease?

Findings and insights from AD/PD 2023

Prothena was honoured to participate in AD/PD 2023, the premiere international Alzheimer’s and Parkinson’s diseases and related neurological disorders conference. Experts in the field from across the globe gathered to discuss the latest findings and share insights from clinical trials and other developments in translational and clinical research.

With a proven treatment pathway against Alzheimer’s disease, this year’s AD/PD conference was unlike any before it. The conference provided a glimpse of the next generation of Alzheimer’s disease therapies targeting accumulations of Aβ protein, as well as parallel advances in biomarker testing, which is important for earlier diagnosis and monitoring of disease progression.

Prothena itself is developing PRX012, an investigational next generation anti-Aβ antibody for treatment of Alzheimer’s disease, and shared new preclinical data at this year’s AD/PD conference. The data demonstrates a superior binding of 20-fold higher affinity to Aβ protofibrils as compared to lecanemab and mediated more robust phagocytic clearance of pyroglutamate-modified Aβ when compared to donanemabii - supporting the ongoing clinical development of PRX012 as a potential best-in-class anti-Aβ immunotherapy that could potentially enable a low-volume, subcutaneous injectable to reduce barriers to treatment.

A symposium for knowledge sharing and treatment advancement

As a way to foster knowledge sharing and advancement of treatment options, Prothena also hosted a symposium at AD/PD 2023 with leading experts in Alzheimer’s disease research to define the next generation of care for patients. The event was chaired by Dr Dennis Selkoe, co-director, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, and a member of the Board of Directors at Prothena. Symposium speakers included Dr Jeffrey Cummings; Joy Chambers-Grundy, Professor of Brain Science and director at the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada Las Vegas (UNLV); and Dr Alireza Atri, director of the Banner Sun Health Research Institute, Sun City, Arizona.

After all, as our chief scientific officer, Wagner Zago, PhD, stated during his presentation at the AD/PD symposium, “today's patients cannot wait for tomorrow's treatment. We all have that responsibility to keep trying different hypotheses and, ultimately, come up with a combination of therapies that can provide even more incremental benefits to the patients.”

Many of the scientists at AD/PD 2023 have dedicated their professional lives to finding new ways to treat, prevent, and ultimately eradicate Alzheimer’s disease. The scientific community has remained confident and steadfast for decades - a persistence that led us to a proven pathway to attack the disease itself.

The future horizon, collaboratively

Excitingly, there’s more to come. Over the last decade, particularly, we’ve witnessed an evolution across Alzheimer’s research, in which learnings from one company’s clinical trials inform the next set of studies – and in turn, the next. This is how science is supposed to work. No one company can solve a problem as big as Alzheimer's disease alone. It takes an entire industry, a whole scientific community to do this.

The next generations of anti-Aβ therapies are promising. Additionally, current research devoted to anti-tau targeting therapies may yield exciting new opportunities in Alzheimer’s disease treatment and spur further drug development. We may encounter more challenges down the road, but we remain confident, steadfast, and optimistic – more so than at any other time in history.

This is an exciting time for Alzheimer’s disease treatment and innovation, from AD/PD 2023 to the recent positive topline clinical data readout further fuelling this moment. I am extremely optimistic about the prospect of new and better treatment options to slow the progression of this ravaging and fatal disease.

References

i Alzheimer’s Association 2023 Alzheimer’s Disease Facts & Figures

ii Prothena AD/PD 2023 Presentation – “Binding Characteristics of Surrogate PRX012 Demonstrate Potent Engagement of Toxic Abeta Protofibrils and Robust Clearance of Pyroglutamate-Modified Abeta”; March 31, 2023

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Dr Donna Masterman
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Dr Donna Masterman