Alzheimer’s: Starting the impossible journey

Not long ago, the prospect of having disease-modifying treatments for Alzheimer’s disease (AD) seemed almost a flight of fancy. Several large pharmaceutical firms exited the field, effectively filing the indication in the “too difficult” draw. But since then, two landmark approvals – of the drugs donanemab (Kisunla, Eli Lilly) and lecanemab (Leqembi, Eisai / Biogen / BioArctic) – have changed the picture.

Despite their modest clinical benefit and problematic side-effect profiles, which have triggered heated arguments about whether they should even have been approved, these monoclonal antibodies are widely being seen as landmarks in the fight against Alzheimer’s.

Patients now have hope that there is something out there which might slow the course of disease. And drug developers have begun to believe that it is worth starting out on the impossible journey.

September was Alzheimer’s Month, and with that in mind pharmaphorum spoke to leaders at two biotechs about latest developments in the field. Judy Walker, MD, is chief medical officer at Scenic Biotech, which is using a genetic modifier approach to uncover natural protective mechanisms in human biology. Martin Zügel, MD, is Chairman and interim CEO of AC Immune, which has a pipeline focused on amyloid and tau targets.

Q. Recent regulatory approvals have marked a significant milestone for Alzheimer's research, but debate continues around their clinical impact. What do these developments tell us about the future direction of the field?

Judy Walker [JW]: These approvals signal that the era of purely symptomatic Alzheimer’s disease drugs is over. Disease‑modifying therapy is now a regulatory and commercial reality, even if they are imperfect and questions remain – namely, the question of, ‘Is a 25 – 40% slowing over 18 months enough to justify the high cost, ARIA risk (i.e., temporary brain swelling or fluid build-up, or brain-bleed risk), and system burden of anti-amyloid therapies?’

With the recent approvals of lecanemab and donanemab, regulators are also redefining what acceptable risk is in early AD, which appears to differ based on region. Future questions we must tackle as a field include the following: How do we make better, safer, and more practical to use agents for AD? How do we tailor agents based on genotype, clinical picture, and co-morbidities? How do we combine agents to optimise outcomes? How can we better diagnose earlier stage, presymptomatic patients for drug intervention?

Martin Zügel [MZ]: The recent approvals for Abeta- (Aβ-) targeting monoclonal antibodies, has shown that the field has benefitted enormously from the use of biomarkers (e.g., Abeta-PET), which relate specifically to the underlying pathology being targeted. In the future, we will see greater use of similar biomarkers to help us select patients earlier and more accurately, and monitor their responses to therapy.

Q. Scenic Biotech's modifier-gene approach is based on uncovering natural protective mechanisms in human biology. What potential do you see for genetic modifiers to unlock new treatment strategies for Alzheimer's disease?

JW: The concept of genetic modifiers is under‑leveraged in general in R&D, but modifier therapies clearly have disruptive potential. Alzheimer’s is an especially fertile ground for modifiers, because we already know that some people carry strong risk factors, yet, remain cognitively intact for decades. There are many APOE4 homozygotes who never develop AD, as well as individuals with considerable amyloid accumulation in brain tissue at autopsy who remained cognitively intact in their lifetime. What is causing this resilience and what is causing disease in others with risk factors?

At Scenic, we’ve developed a platform that allows us to identify such protective mechanisms and we’re developing small molecule therapies to boost these pathways. Whilst anti-amyloid and other therapies focus on removing pathology, modifier therapy could restore protective biology, opening other avenues for treatment, including drug combination protocols.

Q. AC Immune has one of the broadest Alzheimer's pipelines spanning amyloid and tau targets. As our understanding of the disease evolves, which biological pathways and treatment modalities do you think will be most important for the next generation of Alzheimer's therapies? 

MZ: Given the co-pathologies present in most patients, we believe the successful treatment of Alzheimer’s in the future will come down to combination approaches using complementary modalities. This will include the use of active and passive antibody-based immunotherapies and small molecule drugs, which exploit different agents to target individual proteinopathies (e.g., caused by misfolded amyloid beta, tau, a-synuclein, and TDP-43) both inside and outside diseased neurons. 

Q. Looking ahead, what do you think is the biggest opportunity to further accelerate progress in Alzheimer's disease: earlier diagnosis, better biomarkers, novel therapeutic targets, combination therapies, or something else?

JW: All of the above! We clearly need earlier diagnosis and intervention, ideally pre-symptomatic, enabled by strong biomarkers, mechanistic subtyping, and polygenic risk stratification. Any agent administered pre-symptomatically would need to be safe, have a large therapeutic window, and be practical to take over the long term. The field is moving forwards on many of these fronts and the hope is that AD becomes a precision medicine disease, in which novel therapeutic targets, such as modifier genes, are an essential part of the repertoire of therapeutics.

MZ: Precision in identifying the pathologies patients carry and staging their disease will enable more targeted interventions to be applied based on a patient’s specific disease profile. Ultimately, the greatest advances in managing disease more effectively are expected to be achieved through targeted combination approaches.

About the interviewees

Judy Walker, MD, is chief medical officer at Scenic Biotech. She is a biopharmaceutical leader with over 25 years of experience driving cutting-edge drug development in neurodegenerative and rare diseases. A neurologist by training, she has led global clinical programmes across Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, migraine, pain, and rare neurological and neuromuscular disorders. As CMO at Scenic Biotech, Arthex Biotech, and Cerecin, and in senior roles at IQVIA, Teva, and Serono, Walker has shaped CNS pipelines from translational research through post-marketing. Her direct involvement in Alzheimer’s trial design, biomarker-driven development, and regulatory interactions across multiple regions provides a rigorous scientific foundation for her perspectives on the evolving AD therapeutic landscape.

Martin Zügel, MD, is Chairman and interim CEO at AC Immune. He has been serving as the interim CEO of AC Immune since June 2026. Dr Zügel is an experienced executive with 30 years at executive and board level in multinational healthcare companies. He is a board member at Grünenthal, an international company specialising in the neuropharmacology of pain control, where he also chairs the audit committee. In addition, he is currently Chairman of the Board of AMW GmbH, a pioneer of the use of AI to develop biodegradable controlled-release drug delivery systems, and MESI Ltd, an IT-based medical diagnostics company developing integrated hard- and software tools for patient medical assessment. Previously, Dr Zügel served as chairman, director, executive, or advisor with several biotech companies addressing a variety of target medical indications and has also acted as advisor to biotech/pharma investors. Earlier in his career, Dr Zügel was CEO of Merz Pharma GmbH. He holds a Doctorate in Medicine from the University of Tübingen, and a Master’s in Molecular Biology from the University of Massachusetts at Amherst.