Safety and Efficacy of Moroctocog Alfa (AF-CC) in Chinese Patients with Hemophilia A: Results of Two Open-Label Studies

Figures & data

Figure 1 Patient disposition in the authorization study (A) and in the real-world study (B). *Two patients rolled over from the surgical prophylaxis group to the on-demand group and were counted in each group, but were included only once in the overall population.

Table 1 Demographic and Baseline Clinical Characteristics (Safety Analysis Set)

Parameters	Authorization Study (N = 53)	Real-World Study (N = 85)
Age, years, mean (SD)	23.2 (10.0)	9.5 (9.0)
Male, n (%)	53 (100)	84 (98.8)
Chinese nationality, n (%)	53 (100)	85 (100)
Height, cm, mean (SD)	166.8 (12.1)	128.2 (26.8)
Weight, kg, mean (SD)	58.3 (14.9)	30.5 (17.6)
Hemophilia severity, n (%)
Mild	1 (1.9)	4 (4.7)
Moderate	40 (74.5)	32 (37.6)
Severe	12 (22.6)	49 (57.6)
Age at first FVIII replacement, years, mean (SD)	9.0 (9.9)	N/A
Prior FVIII exposure days, n (%)
0	N/A	13 (15.3)
0–100	36 (67.9)	N/A
>100	17 (32.1)	N/A
>0‒20	N/A	10 (11.8)
>20‒50	N/A	14 (16.5)
>50‒150	N/A	19 (22.4)
>150	N/A	29 (34.1)
Positive family history of hemophilia A, n (%)	20 (37.7)	33 (38.8)
Positive virology, n (%)
Hepatitis C antibody	17 (32.1)	N/A
Human immunodeficiency virus	0	N/A

Abbreviations: FVIII, factor VIII; N/A, not assessed; SD, standard deviation.

Table 2 Summary of Efficacy Outcomes

Parameters	Authorization Study				Real-World Study
	8 Hours Postinfusion		24 Hours Postinfusion		On-Demand		Surgical Prophylaxis
	N	%	N	%	N	%	N	%
Investigator Hemostatic Efficacy Assessment scores^a
Excellent	179	28.0	216	33.8	741^b	46.0	10^c	71.4
Good	377	59.0	359	56.2	633	39.3	4	28.6
Moderate	77	12.1	48	7.5	229	14.2	0	0.0
None	6	0.9	3	0.5	5	0.3	0	0.0
Not determined	0	0.0	13	2.0	2	0.1	–	–
“Excellent” or “good” Hemostasis Efficacy Rating Scale scores	556	87.0	575	90.0	1374	85.3	14	100.0
No. of infusions needed to treat each new bleeding event^a	N/A	–	1.2	±0.72	1.6	±0.94	N/A	–
Patients needing one treatment to resolve bleeding event	0	0.0	0	0.0	1015	63.0	0	0.0
LETE incidence	0	0.0	0	0.0	1/1610	0.06	0	0.0
ABR^a	N/A	–	N/A	–	44.76	24.19	N/A	–

Notes: ^aMean (standard deviation). ^bFirst infusion. ^cDay of surgery.

Abbreviations: ABR, annualized bleeding rate; LETE, less-than-expected therapeutic effect; N/A, not available.

Table 3 Characteristics of Patients with Treatment-Emergent Factor VIII Inhibitor

Patient No.	Age (Years)	Disease Severity at Diagnosis	Prior FVIII EDs/Moroctocog Alfa EDs Before Inhibitor Development	Genetic Mutation	Initial Titer/ Peak Titer (BU)^a	Outcome	Clinical^b Significance
Authorization study^c
010	18	Severe	192/12	Intron 22 inversion	7.6/20	Recovered	Significant
030	29	Unknown	100/23	Unknown	0.6/0.6 (transient)	Unknown	Not significant
001	2	Severe (<1%)	30/19	Unknown	2/2	Unknown	Unclear
086	29	Severe (<1%)	20/10	Intron 22 inversion	15/15 (transient)	Recovered	Minimal
081	32	Severe	15/8	Intron 22 inversion	12/22	Not recovered	Significant
069	20	Unknown	12/11	Intron 22 inversion	320/320	Unknown	Significant
106	41	Unknown	Unknown/14	Unknown	0.9/0.9	Not recovered	Not significant
Real-world study—On-demand treatment group
191002	6	Moderate (1–5%)	60/36	NA	16/64	Not recovered	Not significant
041003	5	Moderate (1–5%)	>150/38	NA	2/2 (transient)	Recovered	Not significant
051004	17	Severe (<1%)	>200/28	NA	0.7/0.7 (transient)	Recovered	Not significant
051008	15	Severe (<1%)	>320/32	NA	0.7/0.7 (transient)	Recovered	Not significant
191004	4	Moderate (1–5%)	35/18	NA	1/2	Not recovered	Not significant
191006	4	Moderate (1–5%)	129/29	NA	1/1 (transient)	Recovered	Not significant
Real-world study—Surgical prophylaxis group
061007	47	Mild (>5–40%)	14/16	NA	1.2/1.2 (transient)	Recovered	Not significant

Notes: ^aHigh titer was defined as ≥5 BU. ^bClinical significance was determined by the sponsor and investigator on a case by case basis. ^cThe two patients who were inhibitor positive at screening (ie, not a treatment-emergent adverse event) were excluded from this analysis).

Abbreviations: BU, Bethesda unit; ED, exposure days; FVIII, factor VIII; NA, not assessed.

Table 4 Adverse Events, Regardless of Relationship to Study Drug, Reported in the Authorization Study (N = 53; Safety Analysis Set)

Events	No. of Events	Patients
		n	%
All adverse events	32	19	35.9
Anti-FVIII antibody positive	9	9^a	17.0
Injury	8	6	11.3
Decreased blood potassium	2	2	3.8
Hypersensitivity	2	1	1.9
Joint sprain	2	1	1.9
Diarrhea	1	1	1.9
Gingival bleeding	1	1	1.9
Upper gastrointestinal hemorrhage	1	1	1.9
Pyrexia	1	1	1.9
Hepatic steatosis	1	1	1.9
Fall	1	1	1.9
Joint dislocation	1	1	1.9
Joint injury	1	1	1.9
Arthritis	1	1	1.9

Note: ^aTwo of nine patients who were anti-FVIII positive at screening were excluded from the efficacy and inhibitor rate analyses, but were included in the safety population.

Abbreviation: FVIII, factor VIII.

Table 5 Adverse Events, Regardless of Relationship to Study Drug, Reported by >10% of Patients Overall in the Real-World Study (N = 85; Safety Analysis Set)

Adverse Events, n (%)	On-Demand (n = 73)		Surgical Prophylaxis (n = 14)		Overall (n = 85)^a
	N	%	N	%	N	%
Patients with AEs	65	89.0	10	71.4	74	87.1
Joint swelling	34	46.6	3	21.4	37	43.5
Arthralgia	24	32.9	2	14.3	26	30.6
Nasopharyngitis	18	24.7	0	0	18	21.2
Pain in extremity	18	24.7	0	0	18	21.2
Pyrexia	15	20.5	2	14.3	17	20.0
Peripheral swelling	15	20.5	0	0	15	17.6
Muscle swelling	11	15.1	0	0	11	12.9
Cough	10	13.7	0	0	10	11.8
Fall	9	12.3	0	0	9	10.6
Ecchymosis	9	12.3	0	0	9	10.6

Note: ^aTwo patients rolled over from the surgical prophylaxis group to the on-demand group and were counted in each group, but were included only once in the overall population.