PB0201 - Efanesoctocog Alfa Versus Extended Half-Life Factor VIII Therapies for Prophylaxis in Adolescents and Adults with Severe Hemophilia A: A Matching-Adjusted Indirect Comparison and Meta-Analysis

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

Robert Klamroth, MD, PhD (he/him/his)

Priv. Doz. Dr. med.
Vivantes Klinikum im Friedrichshain, Clinic for Internal Medicine Angiology and Haemostaseology
Berlin, Berlin, Germany

Co-Author(s)

PG

Patricia Guyot

Evidence Synthesis NMA/ITC Lead Modeling
Sanofi, Cambridge, Massachusetts, USA
Cambridge, Massachusetts, United States

Presenting Author(s)

Alix Arnaud, MsC (she/her/hers)

Director, HEOR Rare Blood Disorders
Sanofi, Cambridge, Massachusetts, USA
Cambridge, Massachusetts, United States

Co-Author(s)

AW

Amanda Wilson

HEVA Business Partner - Rare Disease and Rare Blood Disorder Portfolio
Sanofi, Cambridge, Massachusetts, USA
Cambridge, Massachusetts, United States
PW

Piotr Wojciechowski

External consultant
Putnam PHMR, Krakow, Poland
krakow, Malopolskie, Poland
MW

Marlena Wdowiak

Senior Analyst, HEOR DA
Putnam PHMR, Krakow, Poland
Krakow, Malopolskie, Poland
WM

Wojciech Margas

Senior Analyst, HEOR DA
Putnam PHMR, Krakow, Poland
Krakow, Malopolskie, Poland
EG

Ekaterina Gresko

Senior Medical Director, Head MACS Haemophilia
Sobi
Basel, Basel-Stadt, Switzerland
Nana Kragh, MSc

Global HEOR Director
Sobi, Stockholm, Sweden
Stockholm, Stockholms Lan, Sweden

Background: The XTEND-1 study (NCT04161495) demonstrated that once-weekly efanesoctocog alfa (EFA) prophylaxis (PPX) provided prevention of bleeding episodes compared with prior PPX. However, there are no head-to-head clinical trials comparing efficacy of EFA PPX versus approved extended half-life (EHL) FVIII PPX.

Aims: To compare efficacy of PPX with EFA versus PPX with approved EHL FVIII therapies in adolescent and adult patients with severe hemophilia A.

Methods: A systematic literature review was conducted (in Medline, EMBASE, and Cochrane clinical Trials register) to identify phase 3 trials of EHL therapies. Patient-level data was also extracted from XTEND-1 study and for efmoroctocog alfa. Matching-adjusted indirect comparison was used to compare any, joint, and spontaneous bleeds between EFA and respective comparators, except for efmoroctocog alfa where propensity scores were calculated with the relevant available covariates. The results were presented either as mean differences (MD) of annual number of bleeds or incidence rate ratios (IRR) (95% confidence intervals [95% CI]). The estimates from respective comparisons were pooled using random-effect meta-analysis to evaluate the overall difference between EFA and EHL FVIII therapies.

Results: Five trials were identified, assessing prophylactic regimens for EHL therapies: PROLONG-ATE and PROPEL for rurioctocog alfa pegol, A-LONG for efmoroctocog alfa, PATHFINDER 2 for turoctocog alfa pegol, and PROTECT VIII for damoctocog alfa pegol. EFA was associated with significantly lower annualized bleeding rate (ABR) of any bleeding (MD) [95% CI], (─2.24 [─3.24 to ─1.25]), spontaneous bleeding (─1.52 [─2.33 to ─0.72]), and joint bleeding (─1.60 [─2.32 to ─0.88]) versus EHL FVIII therapies (Figure 1). The frequency of any bleeding was reduced by 77% in those receiving EFA compared with EHL (IRR= 0.23 [0.18 to 0.31]) (Figure 2).

Conclusion(s): The prophylactic therapy with EFA was associated with significantly lower ABR (any, spontaneous and joint) compared with approved EHL therapies PPX.
Funding disclosures: This study was funded by Sanofi and Sobi.