Eli Lilly’s promising new drug, Remternetug, is currently in Phase 3 trials. It is aimed at treating Alzheimer’s disease.

How does Remternetug compare to Kisunla (donanemab)?

Remternetug is part of a new wave of Alzheimer’s treatments that target amyloid plaques in the brain, similar to other drugs like donanemab.

J.K. Wall, an Eli Lilly spokesperson, explained that Remternetug “may provide more robust plaque removal” than donanemab. For example, after 41 people were tested for 6 months with remternetug, 75% of the people tested had amyloid cleared from their brains. Compare that to a phase two trial of donanemab, where only 40% of participants treated with donanemab achieved amyloid clearance in that amount of time. 

All these numbers are occurring in remterntug trials, which are expected to be completed in 2025. 

On the other hand, let’s compare these two drugs’ safety profiles. Study results show remternetug may exhibit higher rates of side effects such as brain swelling. In the study results so far, the side effect — known as amyloid-related imaging abnormality, or ARIA — was seen in 10 out of 24 remternetug patients. That’s a 41% rate of ARIA, higher than the rates found in Kisunla (donanemab).

Here’s a comparison of these drugs:

Remternetug

• Mechanism: Targets and clears amyloid plaques using an N3pH-Aß monoclonal antibody¹.
• Efficacy: In early trials, 75% of participants achieved significant amyloid clearance¹.
• Safety: Well-tolerated with no treatment-emergent antidrug antibodies, though some amyloid-related imaging abnormalities (ARIA) were observed¹.
• Current Status: In Phase 3 trials, aiming to enroll 600 participants with early symptomatic Alzheimer’s¹.

Donanemab

• Mechanism: Similar to Remternetug, it targets amyloid plaques but focuses on a different epitope of the amyloid protein².
• Efficacy: Demonstrated significant plaque reduction and cognitive benefits in early trials².
• Safety: Also associated with ARIA, but generally well-tolerated².
• Current Status: Undergoing further trials to confirm long-term benefits and safety².

Lecanemab (Leqembi)

• Mechanism: Targets amyloid plaques and has been shown to slow cognitive decline in early Alzheimer’s².
• Efficacy: Approved in several countries for early Alzheimer’s, showing a slower progression of memory and thinking decline².
• Safety: Similar safety profile with ARIA being a common side effect².
• Current Status: Approved for use in multiple countries, including the US, Japan, and China².

Comparison Summary

• Mechanism: All three drugs target amyloid plaques but may differ in their specific binding sites and mechanisms.
• Efficacy: All have shown promise in reducing amyloid plaques and slowing disease progression, with Remternetug and donanemab still in trial phases.
• Safety: ARIA is a common side effect across these treatments, but they are generally well-tolerated.
• Approval Status: Lecanemab is the most advanced, with approvals in several countries, while Remternetug and donanemab are still undergoing trials.

Remternetug stands out as a second-generation treatment with potential improvements in efficacy and safety over its predecessors²¹. Continued research and clinical trials will be crucial in determining its place in Alzheimer’s therapy.

Mechanism of Action

Remternetug is an N3pH-Aß monoclonal antibody designed to target and clear amyloid plaques in the brain, which are believed to contribute to the progression of Alzheimer’s disease¹. By binding to a specific region of the toxic amyloid protein, Remternetug attracts immune cells to clear these plaques, potentially addressing the root cause of Alzheimer’s symptoms².

Clinical Trial Results

In early-stage trials, Remternetug demonstrated significant amyloid plaque reduction. In a Phase 1 study, 75% of participants receiving doses between 700 to 2800 mg every four weeks achieved amyloid clearance by day 169¹. The drug was well-tolerated, with no treatment-emergent antidrug antibodies detected¹. However, amyloid-related imaging abnormalities (ARIA) were observed in some participants, a common side effect in this class of drugs³.

Phase 3 Trial

The ongoing Phase 3 trial, named TRAILRUNNER-ALZ1, aims to enroll 600 participants with early symptomatic Alzheimer’s disease¹. This double-blind study will evaluate the efficacy and safety of Remternetug over 52 weeks, followed by an additional 52-week extension period. The primary outcome measure is the percentage of patients achieving amyloid plaque clearance on amyloid PET scans¹.

Potential Impact

If successful, Remternetug could represent a significant advancement in Alzheimer’s treatment by providing a robust method for amyloid plaque reduction. This could potentially slow or halt the progression of the disease, offering hope to millions of patients and their families.

Conclusion

Remternetug’s promising early results and ongoing Phase 3 trial highlight its potential as a groundbreaking treatment for Alzheimer’s disease. Continued research and clinical trials will determine its efficacy and safety, paving the way for a new era in Alzheimer’s therapy.