Almost 2,500 attendees flocked to Madrid last week for the 2024 edition of Clinical Trials on Alzheimer’s Disease (CTAD). The first European edition of the conference since 2018 was punctuated by a mood of excitement, with Leqembi (lecanemab) – the second drug that targets Alzheimer’s disease progression by reducing amyloid plaques – now in clinical practice in the US and showing a modest slowing of cognitive decline in early Alzheimer’s patients.
Researchers were hoping to build on this momentum with a host of data readouts in everything from new disease-modifying treatments, repurposed small molecule drugs like insulin, gene therapies, and treatments for Alzheimer’s symptoms including cannabinoids. There was also much anticipation in the diagnostics field, with the first generation of blood-based biomarkers that detect amyloid plaques set to come online next year
Madrid: A Fitting Host City
Only two of the last ten in-person CTADs have been held outside of the US, by far the world’s leading funder of biomedical research, including for Alzheimer’s. However, as members of the organising committee pointed out in the CTAD 2024 opening plenary session, Spain was a fitting destination for this year’s conference (despite the out-of-town Marriott hotel playing host to the event perhaps not showing the most scenic side of the Spanish capital).
“Spain is not only a great place for holidays or football but is also one of the leaders in Alzheimer’s disease research,” began Pascual Sanchez-Juan of the Centro Alzheimer Fundacion Reina Sofia in Madrid. “Spain ranks sixth [globally] in number of publications on Alzheimer’s Disease, and Madrid and Barcelona are in the top ten per cities. Spain is especially strong in clinical trials and is one of the top recruiters in the world due to the fact that we have excellent health professionals and a universal coverage health system.”
Some of the US participants were hopeful that bringing CTAD back to Europe would help spur the continent into making the new generation of Alzheimer’s treatments available to patients on the continent. “I’m a little discouraged that the drugs that we celebrate are not available in Europe,” said Paul S Aisen of the University of Southern California. “[These drugs] are not available in Europe and not funded in the UK. My hope is that with CTAD here in Madrid, we can generate excitement and teach about the progress we’ve made and what’s coming and bring everybody to this same place and have the same availability of Alzheimer’s therapeutics.”
Honouring the Father of Leqembi
The conference began by presenting a lifetime achievement award to Lars Lannfelt, whose groundbreaking research laid the foundation for the development of the Alzheimer’s drug Leqembi.
Lannfelt and his team discovered what became known as the “Swedish” and “Arctic” genetic mutations of Alzheimer’s disease, essential discoveries in our understanding of Alzheimer’s pathology today. This led him to investigate targeting toxic aggregates, rather than plaques, as a therapeutic approach and eventually to co-found the biotech company BioArctic in his native Sweden. Through a partnership with Eisai, BioArctic developed Leqembi, the first FDA-approved drug that modestly slows cognitive decline in Alzheimer’s patients.
In a keynote presentation, Lannfelt emphasised the complex, lengthy process of drug development and his belief that ongoing treatment and improving brain penetration of anti-amyloid drugs are essential for future Alzheimer’s therapies. “Alzheimer’s disease is a chronic disease, and I’m sure it needs chronic treatment,” he said.
Towards Patient-Focused Treatment
Amidst the hype and bluster of scientific conferences, where reams of data readouts claim to represent breakthrough treatment options, it is important to circle back to what patients actually want, need, and can have. That was the theme of a third-day keynote from Rachelle Doody, formerly global head of neurodegeneration at Roche and now chief medical officer and head of development at vaccine-focused start-up Vaxxinity.
Despite there being over seven million people in the United States and 55 million globally with clinical Alzheimer’s symptoms (and probably twice as many still undiagnosed), Doody posited that Alzheimer’s is still widely misunderstood. She cited a UK survey showing that while 68 percent of people could name one fact about Alzheimer’s disease (usually that it involved memory loss), only 11 percent identified Alzheimer’s as a neurodegenerative disease.
This lack of understanding is being compounded by a slew of new information on Alzheimer’s – including the recent controversies around approval, pricing, and reimbursement of new therapies – as well as a shortage of dementia specialists. All of this means that patients and their caregivers are often left struggling to navigate the healthcare system and access the care they need.
Doody therefore proposed greater clarity and context in how healthcare professionals communicate. “What patients and families want is a very clear, demystified, unbiased understanding of what Alzheimer’s disease is and what the treatment options are,” she said. This would be bolstered by “a whole system approach” with countries, states, and healthcare systems working together, as well as doctors “erring on the side of treatment; without this focus, we will struggle to deliver these advancements to those who need them.”
Blood Biomarkers “Ready for Prime Time”?
Doctors are increasingly using blood tests to detect Alzheimer’s biomarkers as they offer a valuable, cost-effective, and less invasive alternative to PET scans and lumbar punctures. While blood tests alone do not diagnose Alzheimer’s, they provide crucial evidence that can support a diagnosis, especially in individuals with mild cognitive impairment or early-stage memory loss.
These tests are currently primarily utilised in research settings and specialised clinics, but in her CTAD 2024 keynote, Washington University’s Suzanne Schindler proclaimed that “high-accuracy blood biomarker tests (BBMs) for Alzheimer’s disease are ready for prime time.” Fluid biomarkers are expected to gain regulatory approval and reimbursement in 2025.
Schindler discussed how these tests, which can detect amyloid and tau proteins linked to Alzheimer’s, have reached an accuracy level comparable to, or even exceeding, existing methods. She cited one study where BBMs achieved 91 percent accuracy in diagnosing the cause of cognitive impairment, compared to 73 percent for a dementia specialist and just 61 percent for primary care doctors.
While accepting that rolling these technologies out globally will require overcoming significant educational, regulatory, and logistical obstacles, Schindler pointed out that work is already underway. The WHO has released guidelines for preferred product characteristics for tests used in poorer countries, while a ‘Global CEO Initiative on Alzheimer’s Disease (CEOi)’ is leading a global effort to prepare for the widespread adoption of Alzheimer’s BBMs into clinical practice.
Schindler also addressed hesitance toward these technologies’ current imperfections, foregrounding their accuracy, potential to be used in more economically diverse settings, and acceptability to more diverse research groups, thereby bolstering clinical trial diversity. “We need to make sure that the perfect is not the enemy of the good,” she concluded.
Image: CTAD 2024 Opening Plenary
Source: CTAD 2024
