A NOVEL BAYESIAN MODELING APPROACH INCREASES PRECISION OF PREDICTED LONG-TERM DURABILITY OF ETRANACOGENE DEZAPARVOVEC FOR THE TREATMENT OF HEMOPHILIA B
Author(s)
Yiyao Shi, PhD1, Xiang Zhang, PhD2, Weining Shen, PhD1, Douglass Drelich, MD2.
1Department of Statistics, California State University, Irvine, CA, USA, 2CSL Behring, King of Prussia, PA, USA.
1Department of Statistics, California State University, Irvine, CA, USA, 2CSL Behring, King of Prussia, PA, USA.
Presentation Documents
OBJECTIVES: Gene therapies offer the promise of addressing the root causes of genetic disorders such as Hemophilia B. However, HTA authorities expressed challenges in assessing their value due to a lack of long-term data. We developed a novel Bayesian (BASE) model to predict the durability of gene therapy for adult patients with hemophilia B (PWHB).
METHODS: The BASE model incorporated 2-year (phase 3) and 2.5 year (phase 2b) factor IX (FIX) levels of adult PWHB receiving etranacogene dezaparvovec. The 5-year predictions were compared against observed 5-year data from follow-up. The 5-year clinical data was then included to update predictions for PWHB with FIX level ≥ 5%, up to 25 years post infusion.
RESULTS: Mean observed FIX values were within the 95% credible interval (CrI) of the corresponding mean prediction for the 3rd, 4th, and 5th year post infusion, e.g. the observed 5 year result was 36.7% (combined Phase 2b/3) and 33.6% (CrI: 24.7%, 39.5%) from the model. The updated BASE model including month 60 data from Phase 2b/3 predicts that 91% of patients would have FIX ≥5% at 25-years post infusion.
CONCLUSIONS: The BASE model generated statistically unbiased estimates and was validated through comparison with observed findings. The predictive results reduce the uncertainty around the long-term durability of etranacogene dezaparvovec suggesting that there is sustained durability anticipated for > 90% of patients over a period of 25 years.
METHODS: The BASE model incorporated 2-year (phase 3) and 2.5 year (phase 2b) factor IX (FIX) levels of adult PWHB receiving etranacogene dezaparvovec. The 5-year predictions were compared against observed 5-year data from follow-up. The 5-year clinical data was then included to update predictions for PWHB with FIX level ≥ 5%, up to 25 years post infusion.
RESULTS: Mean observed FIX values were within the 95% credible interval (CrI) of the corresponding mean prediction for the 3rd, 4th, and 5th year post infusion, e.g. the observed 5 year result was 36.7% (combined Phase 2b/3) and 33.6% (CrI: 24.7%, 39.5%) from the model. The updated BASE model including month 60 data from Phase 2b/3 predicts that 91% of patients would have FIX ≥5% at 25-years post infusion.
CONCLUSIONS: The BASE model generated statistically unbiased estimates and was validated through comparison with observed findings. The predictive results reduce the uncertainty around the long-term durability of etranacogene dezaparvovec suggesting that there is sustained durability anticipated for > 90% of patients over a period of 25 years.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
MSR99
Topic
Methodological & Statistical Research
Disease
SDC: Rare & Orphan Diseases, SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain), STA: Genetic, Regenerative & Curative Therapies