PB0213 - Efanesoctocog alfa vs. Standard Half-Life (Octocog Alfa) FVIII 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)

AT

Alberto Tosetto, MD

Head of hematology
Hematology Department, San Bortolo Hospital, Vicenza, Italy.
Vicenza, Veneto, Italy

Co-Author(s)

Alix Arnaud, MsC (she/her/hers)

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

Presenting Author(s)

Nana Kragh, MSc

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

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
LB

Linda Bystricka

Director, Global Medical Affairs
Sobi, Stockholm, Sweden
Stockholm, Stockholms Lan, Sweden
PG

Patricia Guyot

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

Background: The XTEND-1 (NCT04161495) study demonstrated that once-weekly efanesoctocog alfa (EFA) prophylaxis (PPX) provided superior bleed protection compared with previous standard of care FVIII prophylaxis. However, there are no head-to-head trials comparing efficacy of EFA PPX with approved standard half-life (SHL) rFVIII PPX therapies.

Aims: To compare efficacy of PPX with EFA versus PPX of approved full-length rFVIII SHL therapies in adolescent and adult patients with severe hemophilia A.

Methods: Data from a systematic literature review in Medline, EMBASE, and Cochrane clinical Trials register was used to identify phase 3/4 trials of full-length rFVIII SHL (octocog alfa). Patient-level data from XTEND-1 study were used for EFA. Two most commonly prescribed full-length recombinant SHLs were included. Matching adjusted indirect comparison (MAIC) was used to compare the frequencies of any, treated, joint, and spontaneous bleeds. Matching characteristics included age, presence of target joints for one product, while for another weight, race, previous regimen, and prior bleeds were also included. The results were analyzed as mean number of bleeds per year and the between-treatment effects as mean difference (MD) of annual number of bleeds (95% confidence interval [95%CI]). The overall difference between EFA and SHL was estimated by pooling respective comparisons with random-effect meta-analysis.

Results: Two different products of octocog alfa were included for comparison with EFA. For one product, one phase 3 trial (Tarantino 2004) and one phase 4 trial (Valentino 2012) while for second product two phase 3 trials (Saxena 2016, Kavakli 2015) were identified. EFA was associated with significantly lower bleed rate: any bleeding, (MD [95%CI]) (─3.61 [─4.43, ─2.79]); treated bleeding (─1.55 [─1.89, ─1.20]); spontaneous bleeding (─2.52 [─3.31, ─1.72]); and joint bleeding (─3.42 [─4.77, ─2.08]) compared with full-length rFVIII SHL therapies (Figure 1).

Conclusion(s): Once weekly PPX with EFA resulted in significantly lower bleeding rates (all, treated, spontaneous, and joint) versus full-length rFVIII SHL therapies.