Cost comparison of efanesoctocog alfa vs conventional factor VIII therapies for major surgeries in patients with severe hemophilia A

Key Points

• •This study compared the costs of SHL, EHL, and high-sustained FVIII products for surgical management in people with severe hemophilia A.
• •The high-sustained FVIII therapy efanesoctocog alfa resulted in 3 to 5.5 times lower consumption and may save $38 947 to $81 000 per surgery.

Visual Abstract

Abstract

We estimated total costs for perioperative hemostatic management with standard half-life (SHL), extended half-life (EHL), and high-sustained (efanesoctocog alfa) factor VIII (FVIII) products in people with severe hemophilia A. The data on dose, total factor consumption, and target FVIII activity for major surgeries were collected from US prescribing information and phase 3 clinical trials. The differences in the total factor consumption and total costs between therapies were compared. The median total factor consumption per major surgery involving octocog alfa (SHL), rurioctocog alfa pegol (EHL), efmoroctocog alfa (EHL), and efanesoctocog alfa was 910, 629, 493, and 163 IU/kg, respectively. The total factor costs were $162 308, $147 104, $120 233, and $81 286, respectively. Efanesoctocog alfa resulted in $81 022 to $38 947 savings vs SHL/EHL therapies per surgery. The perioperative management with efanesoctocog alfa was estimated to be markedly more economical than that with SHL and EHL therapies due to its high-sustained factor activity.

Introduction

Hemophilia A is a rare, X-linked hereditary bleeding disorder characterized by a deficiency of factor VIII (FVIII), resulting in decreased thrombin generation, impaired hemostasis, and an increased risk of bleeding.¹ The condition is categorized by residual FVIII plasma activity: mild (>5%-40%), moderate (1%-5%), or severe (<1%).^2,3 Globally, hemophilia A affects ∼17.1 per 100 000 male births, with severe cases accounting for about 6 per 100 000 males.⁴ In the United States, the estimated prevalence stands approximately at 12 per 100 000 men, which translates to ∼30 000 to 33 000 affected individuals.^5,6

The impaired hemostasis in people with severe hemophilia A (PwHA) results in frequent spontaneous bleeding episodes, predominantly in the joints (hemarthrosis, ∼80% of all bleeding events), as well as increasing the risk of excessive bleeding, morbidity, and mortality during surgical procedures. Therefore, for PwHA, adequate FVIII replacement therapy is essential throughout the perioperative period to ensure hemostasis, prevent excessive bleeding complications and promote healing.^2,7 The World Federation of Hemophilia recommends maintaining peak FVIII activity within the 80% to 100% range preoperatively for major surgeries (eg, orthopedic, cardiovascular, intra-abdominal, intracranial surgical procedures). Following the surgery, this activity should be tapered to 60% to 80% on days 1 to 3, 40% to 60% on days 4 to 6, and 30% to 50% on days 7 to 14 to ensure adequate hemostasis and minimize the risk of complications.^2,8

For perioperative management, standard half-life (SHL) FVIII products typically require frequent intravenous infusions (every 8-12 hours) to maintain the World Federation of Hemophilia–recommended target FVIII activity. In contrast, extended half-life (EHL) FVIII products provide longer dosing intervals (every 12-24 hours). Both SHL and EHL FVIII products necessitate frequent dose adjustments during surgery.^2,8, 9, 10, 11 Thus, perioperative management with these products puts a substantial economic burden on health care systems and PwHA.

Efanesoctocog alfa is a first-in-class, high-sustained FVIII replacement therapy (also known as ultralong FVIII) approved for prophylaxis and treatment in PwHA of all ages in Europe and the United States. It is designed to prolong the half-life by decoupling FVIII from the endogenous von Willebrand factor, thereby overcoming the von Willebrand factor–imposed half-life ceiling.12, 13, 14 An indirect comparison demonstrated that prophylaxis with efanesoctocog alfa was associated with improved bleeding protection compared with the existing EHL and SHL therapies in PwHA without inhibitors.¹⁵ Although the XTEND clinical program¹⁶ has demonstrated the clinical efficacy of efanesoctocog alfa in surgical management, its economic impact in this context has not been quantified.

This study estimated and compared the cost of efanesoctocog alfa with that of the existing FVIII replacement therapies for perioperative hemostatic management in PwHA undergoing major surgeries.

Study design

Data sources

The data on FVIII consumption, including dosing regimens, administration frequency, and preoperative and postoperative target FVIII activity for major surgeries, were extracted from the pivotal clinical trials mentioned in the US prescribing information (PI) for octocog alfa (SHL),^17,18 rurioctocog alfa pegol (EHL),^19,20 efmoroctocog alfa (EHL),^21,22 and efanesoctocog alfa.^14,16

Cost analysis

Cost calculations were based on the wholesale acquisition cost (WAC) projected for 2025. The total factor consumption was calculated for specified perioperative periods: the hospitalization duration for octocog alfa, 7 days for rurioctocog alfa pegol, and 14 days for both efmoroctocog alfa and efanesoctocog alfa. The average weight for males in the United States aged ≥20 years was based on the data from the National Center for Health Statistics data.²³

The following formula was used for cost estimation: total cost = total volume administered (IU/kg) × average US adult male weight (91 kg) × cost per IU ($/IU).

A comparative analysis was conducted to evaluate the differences in the total factor consumption and associated costs across therapies.

Results and discussion

The clinical trial data from registrational studies referenced in the PI were available for all comparators, enabling the comparison of factor consumption across studies. Table 1 provides the descriptions and perioperative factor consumption data extracted from clinical trials in the PI for each FVIII replacement therapy, along with their respective WAC.

Table 1.

FVIII consumption and associated WACs estimated for a 91-kg adult male patient undergoing major surgery during the perioperative period

Factor therapy	Clinical data source	Clinical data description	Reported perioperative period	Median (range) FVIII consumption (IU/kg) during the entire perioperative period	Cost ($/IU)	Postoperative outcomes
Octocog alfa	Registrational study in the FDA label17,18	58 patients (aged ≥5 y) with severe hemophilia A who underwent 65 surgical procedures including 22 major surgeries∗	During hospitalization	910 (228-1825)	1.96	100% of surgeries were rated excellent/good; 2 postoperative bleeding episodes; BT required in 12 surgeries18
Rurioctocog alfa pegol	Phase 3 clinical study in the FDA label (NCT01913405)19,20	21 previously treated male patients (aged ≥12-75 y) with severe hemophilia A who underwent 21 major surgeries†	7 d	629 (464-1457)	2.57	100% rated excellent; 5 postoperative bleeding episodes (2 requiring additional treatment); BT needed for 4 surgeries20
Efmoroctocog alfa	Phase 3 extension studies in the FDA label (NCT01181128 and NCT01454739)21,22	21 patients (aged ≥12 y) with severe hemophilia A who underwent 23 major surgeries‡	14 d	493 (121-733)	2.68	100% rated excellent/good; 1 postoperative bleeding episode; BT required in 3 surgeries22
Efanesoctocog alfa	Phase 3 clinical study in the FDA label (NCT04161495)14,16,24	11 patients (aged ≥12 y) with severe hemophilia A who underwent 12 major surgeries§	14 d	163 (45-361)	5.47	100% rated excellent; no postoperative bleeding episodes; no BT required24

BT, blood transfusions; CVAD, central venous assist device; FDA, US Food and Drug Administration.

^∗Major surgeries included hip replacement, knee and shoulder prosthesis arthroplasty, bilateral complex total knee arthroplasties, and ankle fusion and replacement.

^†Major surgeries included orthopedic surgeries (knee replacement, arthroscopic synovectomy, alloplastic knee surgery, hip replacement and revision, elbow cyst extirpation, needle removed from elbow, and Achilles tendon reconstruction) and nonorthopedic surgeries (multiple tooth extractions, CVAD placement, and gastric band insertion).

^‡Major surgeries included ankle fusion, appendectomy, arthroscopy, endoscopic third ventriculostomy, laparoscopic inguinal hernia repair, spinal surgery, unilateral elbow arthroplasty, unilateral hip arthroplasty, unilateral knee arthroscopy, bilateral knee arthroplasty, unilateral knee arthroplasty, and amputation.

^§Major surgeries included cubital tunnel release and ulnar nerve transposition, knee and hip replacements, tooth extraction, osteosynthesis material removal, laparoscopic hernia repair, neurolysis of ulnar nerve, and removal of implanted devices from bone.

The total factor costs for perioperative management during major surgery were calculated for a hypothetical adult patient weighing 91 kg across 4 FVIII replacement therapies. Efanesoctocog alfa demonstrated the lowest total cost at $81 286, followed by efmoroctocog alfa at $120 233, rurioctocog alfa pegol at $147 104, and octocog alfa at $162 308 (Figure 1).

Figure 1.

Total factor costs per major surgery involving SHL, EHL, and high-sustained FVIII replacement therapies. The reported perioperative period was during hospitalization for octocog alfa, 7 days for rurioctocog alfa pegol, and 14 days for both efmoroctocog alfa and efanesoctocog alfa.

The perioperative management with efanesoctocog alfa demonstrated significant reductions in both factor consumption and associated costs compared with other FVIII replacement therapies. Efanesoctocog alfa showed a 5.5-fold reduction in factor consumption compared with octocog alfa, with associated cost savings of $81 022. Similarly, efanesoctocog alfa demonstrated 3.9-fold and 3.0-fold reductions in factor consumption compared with rurioctocog alfa pegol and efmoroctocog alfa, resulting in cost savings of $65 818 and $38 947, respectively.

This analysis demonstrates that efanesoctocog alfa could lead to substantial cost savings in the perioperative management of major surgeries in PwHA compared with the existing FVIII replacement therapies.

To our knowledge, this study represents the first comparison of the economic impact of efanesoctocog alfa with SHL and EHL FVIII products specifically in the perioperative setting. It addresses a critical evidence gap by estimating the potential cost advantages of this high-sustained FVIII therapy in a clinical context. As health care systems worldwide need to balance clinical outcomes with economic sustainability, such comparative cost analyses are crucial for informed decision-making.

Surgical prophylaxis using SHLs and EHLs reduces the risk of intraoperative or postoperative bleeding complications and leads to better surgical outcomes in PwH.²⁵ However, frequent dosing is required to maintain FVIII activity, which results in a substantial economic burden. The findings indicate that the reduced factor consumption observed with efanesoctocog alfa translates to practical advantages in surgical management. The extended dosing interval (every 48-72 hours) in contrast to conventional protocols (every 8-24 hours) potentially simplifies postoperative care, thereby reducing the treatment burden. This simplified dosing schedule may also decrease the complexity of maintaining target FVIII activity throughout the surgical period.²⁴ Although the current analysis focused on major surgeries, data from the XTEND studies suggest that efanesoctocog alfa may provide similar or greater cost advantages compared to other FVIII products for minor procedures. For 13 of the 18 minor surgeries, a single dose was sufficient, whereas for the remaining 5, no preoperative dose was required (routine prophylaxis was sufficient).²⁴ Fewer factor infusions may lead to reduced nursing time, a decreased need for laboratory monitoring and potentially shorter hospital stays or fewer clinic visits after discharge. These additional benefits, although not quantified in our analysis, could further enhance the economic value proposition of efanesoctocog alfa in surgical settings.

This study has several limitations that should be considered when interpreting its results. First, although average WACs were used, actual costs may vary significantly among hospitals and pharmacies, potentially affecting the generalizability of our findings. Second, this analysis likely underestimates the surgical costs of octocog alfa compared with other products as it only considered the medication volume used during hospitalization, rather than the full perioperative period. Because the complete perioperative period typically extends beyond the hospital stay, as reported in other registrational studies, the actual surgical costs associated with octocog alfa are likely higher than the calculated costs. Third, the analysis underestimates the surgical cost of rurioctocog alfa pegol as the perioperative period reported for it was shorter (1 week) than that for efmoroctocog alfa and efanesoctocog alfa (2 weeks). Extending the perioperative treatment duration for octocog alfa and rurioctocog alfa to 2 weeks (to use consistent perioperative periods for all 4 drugs) would at least double the estimated total treatment costs for these therapies. Fourth, the analysis was restricted to major surgeries for consistency; however, the exact types of major surgeries varied among studies, potentially introducing variability in factor requirements. Fifth, our calculations were based on the average adult male weight (91 kg) in the United States, which may not accurately represent the diverse population with severe hemophilia A undergoing surgery. Although absolute cost magnitudes would vary with patient weight, the relative cost differences and overall economic conclusions would remain unchanged. Sixth, factor consumption data used to estimate total treatment costs were based on the clinical trials referenced in the US PI for these FVIII products. Although clinical trial data may overestimate actual consumption due to factors such as nonadherence, product wastage, or dose modifications in real-world settings, it provides valuable insights into treatment approaches, health care resource utilization, and treatment burden in the hemophilia population. Future studies in real-world scenario are required to get insights on actual consumption of efanesoctocog alfa during perioperative management of major surgeries. Lastly, the analysis lacks information on laboratory data required to assess whether the target factor activity was achieved, which is essential for assessing the adequacy of perioperative hemostatic management.

In conclusion, this analysis demonstrated that the perioperative management of major surgeries in PwHA with efanesoctocog alfa could be more economical than that with SHL and EHL therapies. This cost reduction can be attributed to the high-sustained FVIII activity of efanesoctocog alfa and reduced factor consumption during the reported perioperative period.

Conflict-of-interest disclosure: J.M.S. reports honoraria from Bayer, BioMarin, Genentech, and Sanofi. N.K. is an employee of Sobi and may hold stocks and/or stock options in Sobi. D.Q. reports speakers’ bureau participation for Sanofi, Novo Nordisk, CSL Behring, and HEMA Biologics; and consultancy for Genentech, Bayer, Novo Nordisk, Shire, CSL Behring, and HEMA Biologics. A.P.W. reports honoraria from HEMA Biologics, Pfizer, Novo Nordisk, Genentech, uniQure, Octapharma, Takeda, Sanofi, CSL Behring, and Bayer. A.A., I.A., L.A., A.W., and D.B. are employees of Sanofi and may hold shares and/or stock options in Sanofi.