Closing the Gaps in Getting New Alzheimer’s DMTs to Patients

As the exclusive hosting partner for the recent 13^th Annual Alzheimer’s and Parkinson’s Drug Development Summit in Boston, MA , Lumanity opened the conference, with a crucial panel “What Have we Learned from the Last 12 Months of Alzheimer’s Drug Development?” chaired by Ginger Johnson, PhD SVP, Strategy Consulting addressing key learnings in the past year of Alzheimer’s Disease (AD) drug development, as well as potential challenges and promising developments in this critical therapeutic space. Panelists included premier leaders across major AD pharmaceutical programs:

• Eric Siemers, Chief Medical Officer at Acumen Pharmaceuticals
• Alessandro Biffi, Associate Vice President of Eli Lilly
• Elena Dale, Executive Director of Neuroscience at Bristol Meyers Squibb

Key Takeaways

This discussion highlighted the immense progress that has been made across the AD treatment landscape, in particular, the fact that we now have two marketed disease-modifying Aβ mAbs, Leqembi (lecanemab) and Kisunla (donanemab), with demonstrated clinical benefit. In addition, innovative solutions such as AI, teleneurology, and advanced patient profiling to support treatment personalization were discussed as potential near-term breakthroughs.

However, several outstanding gaps and questions were raised that the field will need to address to advance AD drug development and enable broader uptake of disease-modifying therapies (DMTs):

• Inadequate Treatment Infrastructure: Currently approved Aβ mAbs require early and accurate diagnosis of AD via PET imaging, broad access to IV infusion chairs, and consistent availability of MRI scanners to monitor for Amyloid-Related Imaging Abnormalities (ARIA). Other AD therapies in development pose even greater challenges for getting therapy to patients, including ASOs which currently require intrathecal administration. The industry must find effective solutions to these bottlenecks to enable the widespread adoption of these therapies.
• The Problem of ARIA: 1^st generation Aβ DMTs carry significant risk of ARIA, resulting in hesitancy amongst AD-treating physicians and AD patients, with specific product warnings for ApoE ε4 homozygotes and patients with pre-treatment microhemorrhages and/or superficial siderosis. In fact, the EMA recently rejected Kisunla due to this elevated safety risk. It is unclear whether this is a class effect, or if 2^nd generation mAbs will be able to solve this important safety issue.  Next generation shuttle technologies may also reduce ARIA risk using active transport mechanisms to enhance the delivery of anti-amyloid monoclonals across the blood-brain barrier.
• Need for Blood-Based Biomarkers: Will plasma biomarkers (such as pTau217) truly be able to supplant PET or CSF for confirmation of AD pathology in clinical trials, and ultimately, for treatment initiation decisions in the real world? If so, blood-based biomarkers bring the promise of dramatically reduced cost and improved access for a definitive AD diagnosis, opening the possibility of broad-based early screening for millions of patients by primary care physicians.
• Monotherapy vs. Combination Therapy: With two Aβ-targeting treatments currently available and more in development, these therapies are expected to become the cornerstone of treatment for eligible patients. However, Aβ pathology is not the only potential target. There are also several anti-Tau therapies in clinical development, as well as drugs targeting immune pathways and other systemic mechanisms, including GLP-1 agonists. Combining treatments that target Aβ with those addressing other AD-related pathologies may offer greater therapeutic benefits. Therefore, companies must explore innovative methods for clinical trial recruitment and study design to maximize the value of these programs while considering how positive results will translate to real-world clinical settings.

Despite these challenges, it is without question that AD drug development is in a golden era. With continued investment into AD across the pharmaceutical and biotech industry, we look forward to supporting efforts to bring these groundbreaking treatments into the hands of patients.

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