Roche is evaluating the possibility of seeking accelerated approval in the U.S. for its investigational Alzheimer's disease drug, trontinemab, following encouraging early data. The decision hinges on whether ongoing trials confirm the drug's ability to significantly reduce amyloid protein levels, a key indicator of cognitive decline in Alzheimer's patients. Executives presented these considerations at a recent investor event, highlighting the potential for trontinemab to reach the market sooner than initially anticipated, pending Phase 3 trial outcomes.
Potential for Accelerated Approval
The FDA has previously granted accelerated approvals to Alzheimer's drugs that demonstrate a reduction in amyloid plaques in the brain, such as Eisai and Biogen’s Leqembi. Roche aims to leverage this precedent, with Hanno Svoboda, trontinemab’s lifecycle leader, indicating the company will explore opportunities to expedite the drug's availability. Trontinemab is currently in Phase 2 testing, and recent data suggests it may clear amyloid more rapidly than Eli Lilly's Kisunla.
Novel Mechanism of Action
Trontinemab distinguishes itself from other Alzheimer's drugs through its enhanced ability to penetrate the blood-brain barrier. This design could lead to more potent and precise drug effects at lower doses, though this hypothesis requires confirmation in larger, late-stage trials. Phase 2 study results have demonstrated the drug's potential, with amyloid cleared from the brains of most volunteers in the highest two dose groups after 28 weeks of treatment. While cross-trial comparisons are challenging, 17% of participants in Kisunla's Phase 3 trial experienced similar amyloid clearance at 24 weeks.
Dosing and Safety Profile
The rapid effects observed with trontinemab could enable Roche to explore a low-frequency maintenance dosing regimen to prevent amyloid levels from rebounding, according to Svoboda. The ongoing mid-stage trial is expanding to include 120 volunteers, some of whom will receive a placebo.
Initial safety data from the study revealed one participant death due to brain bleeding, although this individual had a pre-existing condition (superficial siderosis) that increased their risk. Roche has since adjusted its enrollment criteria accordingly. Furthermore, trontinemab treatment has shown lower rates of ARIA (amyloid-related imaging abnormalities), indicating brain swelling, compared to other drugs. Less than 10% of trontinemab-treated volunteers experienced ARIA, compared to over 20% for Kisunla and above 10% for Leqembi in their respective Phase 3 trials.
While trontinemab had higher rates of infusion-related reactions compared to Leqembi and Kisunla, Roche has successfully reduced these reactions to below 40% at the two highest doses tested.
