Quantification of Benefit-Risk in Amyloid-Targeting Therapies for Cognitively Unimpaired Alzheimer's Disease

Oralee J Varnado¹, Matthew Quaife², Jaein Seo³, Antje Tockhorn-Heidenreich¹, Nalin Payakachat¹, Yasmijn Slaghekke², Álvaro Alberto Gutiérrez-Vargas², 

J. Scott Andrews¹, Niklas Mattsson-Carlgren^4,5

¹Eli Lilly and Company, Indianapolis, IN, USA

²PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, London, UK

³PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA

⁴Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Medical Faculty, Lund University, Lund, Sweden

⁵Memory Clinic, Skåne University Hospital, Malmö, Sweden

Sponsored by Eli Lilly and Company

BACKGROUND

Study Aim

OBJECTIVES

STUDY DESIGN

 KEY RESULT

Choosing Treatment

■Across the choice tasks, 38.2% of participants never opted out of treatment.

■Participants were significantly more likely to choose a treatment option (A or B) rather than opting out (p<0.001).

Relative attribute importance

■Once opting in, treatment choices were influenced by ATT attributes to varying extents.

■Treatment benefits related to delaying progression to AD with MCI were the most influential drivers of treatment preference, with similar importance across the three benefit attributes (Figure 2).

■Risk-related attributes were less influential in treatment decision-making, including chance of having an abnormal brain scan (16.6%) and time until abnormal brain scan improvement or no new signs (3.5%).

 Maximum Acceptable Risk of ARIA

■For a treatment that reduces the probability of progression to AD with MCI by 10% at 2 and 3 years, participants were willing to accept a 23.9% and 23.2% increase, respectively, in the risk of ARIA.

■For a treatment that delays progression to AD with MCI by 6 months, participants were willing to accept a 9.5% increase in the risk of ARIA.

■To reduce the ARIA resolution time from 6 months (+3 MRI scans) to 1 months (+1 MRI scan), participants were willing to accept 2.4% increase in the risk of ARIA.

■A shorter ARIA resolution time with associated monitoring was not a meaningful driver in treatment decision making.

 Preference-based Benefit-Risk Assessment

■The ATT profile was preferred over no treatment (Figure 4).

■The ATT profile was perceived to have benefits that outweigh its risks, with a significantly higher net benefit-risk score than the no-treatment profile (37.3 vs 29.6; difference = 7.8; p<0.001).

■The largest contributors to the net benefit-risk score were reductions in probability of progression to AD with MCI at 2 years, while risk-related attributes negatively contributed to overall benefit-risk.

 CONCLUSIONS

 Acknowledgments:

Medical writing was provided by Louisa Ludwig-Begall, PhD (PPD clinical research business of Thermo Fisher Scientific) and Evangeline Ann Daniel (Eli Lilly and Company) in accordance with Good Publication Practice guidelines and was funded by Eli Lilly and Company.

Disclosures:

Oralee Johnson Varnado, Antje Tockhorn-Heidenreich, Nalin Payakachat, Alice Farquharson, and J. Scott Andrews: Employee of Eli Lilly and Company and minor shareholder. Matthew Quaife and Jaein Seo: Employee of Thermo Fisher Scientific and minor shareholder. Yasmijn Slaghekke and Álvaro Alberto Gutiérrez-Vargas: Employee of Thermo Fisher Scientific. Niklas Mattsson-Carlgren: Has received speaker/consultancy fees from BioArctic, Biogen, Eli Lilly, Merck, Novo Nordisk, Owkin, Positrigo and Roche.

References:

1. Sperling RA et al. Alzheimers Dement. 2011;7(3):280–292.

2. AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid (NCT04468659).

3. A Donanemab (LY3002813) Study in Participants With Preclinical Alzheimer's Disease (TRAILBLAZER-ALZ 3) (NCT05026866)

4. Sims JR et al. JAMA. 2023;330(6):512–527.