Table 1.

Summary of clinical registration studies of rAHF-PFM

Study	Population	Design	Treatment	Endpoints	Efficacy results
Pivotal16	Criteria: FVIII ≤2 IU/dL; age ≥ 10 years; PTP (≥ 150 EDs) Enrolled • N=111 • Median age: 18 years • 96% FVIII <1 IU/dL • 108 treated Per-protocol • N=30	Parts 1 and 3: PK Part 2: open label, uncontrolled determination of hemostatic efficacy of prophylaxis for ≥75 EDs	Prophylaxis: 3 to 4×/week at 25 to 40 IU/kg for ≥ 75 EDs	Bioequivalence of rAHF-PFM relative to RECOMBINATEa PK Hemostatic efficacy	Treatment of bleeds • 93% of bleeds (473/510) required 1 or 2 infusions • Excellent or good for 439/510 (86%) • Excellent or good for 80% of spontaneous • Excellent or good for 87% of trauma-related ABRb • Overall: 6.3 bleeds/pt/y • Nonadherent vs adherent:c  ○ Mean of 9.9 vs 4.4 (P<0.03). • 32 patients (30%) did not bleed during prophylaxis
Continuation21	Criteria: completion of pivotal study Enrolled: N=81 Per-protocol • N=22 ITT • N=34	Open-label, uncontrolled Part 1: PK Part 2: hemostatic efficacy during prophylaxis or episodic treatment	a. 3 to 4× per week at 25–40 IU/kg for ≥75 EDs b. Investigator-modified prophylaxis for ≥75 EDs c. Episodic therapy	PK after 75 EDs Hemostatic efficacy	Treatment of bleeds • 88.5% of treated bleeds (726/820) required 1 or 2 infusions ABR, mean, by regimen • Standard prophylaxis: 6.0 • Modified prophylaxis: 4.8 • Episodic: 18.5. • Adherent vs nonadherentc  ○ Mean of 7.9 vs 4.5 • 11 of 81 patients (14%) did not bleed during prophylaxis
Pediatric14	Criteria: FVIII ≤2 IU/dL; age <6 years; PTP (≥50 EDs) Enrolled • N=53 (1 female) • Age: 1–5 years; mean 3.1 years • Treated: N=53	As described for continuation study	Planned: as described for continuation study except that standard prophylaxis was 3–4 times/week at 25–50 IU/kg and duration of prophylaxis was ≥46 weeks/year	Hemostatic efficacy	Treatment of bleeds • 90.1% (42/354) required 1 or 2 infusions • Excellent or good for 332/354 (93.8%) ABR, median, by regimen • Standard prophylaxis: 4.0 • Modified prophylaxis: 4.4 • Episodic: 24.4 • 9 patients (8 on prophylaxis; 1 on episodic tx) did not have a bleeding episode during the study Joint ABR, median by regimen • Prophylaxis: 0 • Modified prophylaxis: 0 • Episodic: 14.2

Notes:

^aRECOMBINATE is manufactured by Baxter Healthcare, Westlake Village, CA, USA

^bABR is given in units of bleeds/patient/year

^cadherent was defined as 25–40 IU/kg per infusion for >80% of the prophylactic infusions at a frequency of 3–4 times per week for 80% of the time on study.

Abbreviations: N, number; ABR, annual bleed rate; ED, exposure day; FVIII, factor VIM; PK, pharmacokinetic; pt, patient; PTP, previously treated patient; RECOMBINATE, Recombinate rAHF; SD, standard deviation; tx, therapy; wk, week; y, year; ITT, intent-to-treat; vs, versus; rAHF-PFM, recombinant antihemophilic factor produced using a plasma/albumin-free method.