Safety profile of FABHALTA
Serious infections caused by encapsulated bacteria1
FABHALTA, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.1
Because of the risk of serious infections caused by encapsulated bacteria, FABHALTA is available only through a REMS program called the FABHALTA REMS.1
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Contraindications
FABHALTA is contraindicated:
In patients with serious hypersensitivity to FABHALTA or any of the excipients1
For initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b1
APPLY: A head-to-head study of C5i-experienced (eculizumab or ravulizumab) adults with PNH1
Safety profile of FABHALTA in the head-to-head APPLY trial vs C5is
Adverse reactions reported in >5% of adults with PNH treated with FABHALTA in APPLY (24-week randomized treatment period)
ADVERSE REACTIONS | FABHALTA (N=62) n (%) | C5is (eculizumab or ravulizumab) (N=35) n (%) |
Headachea | 12 (19) | 1 (3) |
Nasopharyngitisb | 10 (16) | 6 (17) |
Diarrhea | 9 (15) | 2 (6) |
Abdominal paina | 9 (15) | 1 (3) |
Bacterial infectionc | 7 (11) | 4 (11) |
Nausea | 6 (10) | 1 (3) |
Viral infectiond | 6 (10) | 11 (31) |
Arthralgia | 5 (8) | 1 (3) |
Thrombocytopeniaa | 4 (6) | 0 |
Dizziness | 4 (6) | 0 |
Systemic hypertensiona | 4 (6) | 0 |
Lipid disordere | 4 (6) | 0 |
aIncludes similar terms.
bNasopharyngitis contains: rhinitis allergic, upper respiratory tract infection, pharyngitis, rhinitis.
cBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial.
dViral infection contains: COVID-19, herpes zoster, oral herpes, nasal herpes, influenza A virus test positive, influenza.
eLipid disorder contains: dyslipidemia, blood cholesterol increased, low-density lipoprotein increased, hypercholesterolemia, blood triglycerides increased, hyperlipidemia.
Serious adverse reactions were reported in 2 (3%) patients with PNH who received FABHALTA. They included pyelonephritis, urinary tract infection, and COVID-19
Rash was reported in 2 patients (3%)
Of the 37 FABHALTA-treated patients who had normal platelet counts at baseline, 43% experienced any grade thrombocytopenia during the randomized treatment period
Three FABHALTA-treated patients experienced decreased platelets that worsened to grade ≥3 from baseline (1 patient with normal platelets that worsened to grade 4; 1 patient with baseline grade 1 that worsened to grade 4; and 1 patient with baseline grade 3 that worsened to grade 4)
No patient discontinued FABHALTA or C5is due to an adverse reaction during the 24-week randomized treatment period and no patient discontinued FABHALTA due to an adverse reaction during the 24-week extension phase. Two patients discontinued FABHALTA due to pregnancy (one each in the randomized treatment period and extension period).2,3
Clinical breakthrough hemolysis (BTH) and major adverse events (MAVEs)
ADDITIONAL END POINTS
Patients on FABHALTA experienced an annualized rate of clinical breakthrough hemolysis of 0.07 and 0.67 with C5is3,*,✝
The data from this additional analysis are descriptive in nature, presented for observation only. No formal conclusions or comparisons between the 2 treatment arms can be made. The planned power for the hypothesis testing was low.
During the 24-week randomized treatment period, 2/62 patients (0.07 annualized rate) experienced clinical BTH with FABHALTA vs 6/35 (0.67 annualized rate) with C5is (eculizumab or ravulizumab) (95% CI, 0.02-0.61)
*Clinical BTH was defined as meeting clinical criteria (either decrease of Hb level ≥2 g/dL compared with the last assessment or within 15 days; or signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia, or any other significant clinical PNH-related signs and symptoms) and laboratory criteria (LDH >1.5 x ULN and increased as compared with the last 2 assessments).3
†Assessed between Days 1 and 168.3
‡BTH and MAVEs were reported from the start of FABHALTA to Day 336.4
§Patients who continued FABHALTA in the 24-week extension period: n=62; patients who switched from anti-C5 antibody to FABHALTA in the 24-week extension period: n=34.4
There was no significant statistical difference in the annualized rates of major adverse vascular events (MAVEs)II between FABHALTA and C5is (0.03 vs 0, respectively; 95% CI, -0.03-0.10)3,†
The data from this additional analysis are descriptive in nature, presented for observation only. No formal conclusions or comparisons between the 2 treatment arms can be made.
During the 24-week randomized treatment period, 1 patient experienced transient ischemic attack in the FABHALTA arm, which was deemed unrelated to treatment by the investigator, vs 0/35 with C5is (eculizumab or ravulizumab)
†Assessed between Days 1 and 168.3
IIThe definition of MAVEs included: acute peripheral vascular occlusion, amputation, cerebrovascular accident, dermal thrombosis, gangrene, hepatic/portal vein thrombosis, mesenteric/visceral arterial thrombosis, myocardial infarction, pulmonary embolus, renal arterial or vein thrombosis, thrombophlebitis/deep vein thrombosis, transient ischemic attack, and unstable angina.3
‡BTH and MAVEs were reported from the start of FABHALTA to Day 336.4
§Patients who continued FABHALTA in the 24-week extension period: n=62; patients who switched from anti-C5 antibody to FABHALTA in the 24-week extension period: n=34.4
APPOINT: A study of complement inhibitor–naive adults with PNH1
Safety profile of FABHALTA in the APPOINT trial
Adverse reactions reported in >5% of adults with PNH treated with FABHALTA in APPOINT (24-week core treatment period)1
ADVERSE REACTIONS | FABHALTA (N=40) n (%) |
Headachea | 11 (28) |
Viral infectionb | 7 (18) |
Nasopharyngitisc | 6 (15) |
Rashd | 4 (10) |
Abdominal paina | 3 (8) |
Diarrhea | 3 (8) |
Lipid disordere | 3 (8) |
aIncludes similar terms.
bViral infection contains: COVID-19, herpes zoster, oral herpes, nasal herpes, influenza A virus test positive, influenza.
cNasopharyngitis contains: rhinitis allergic, upper respiratory tract infection, pharyngitis, rhinitis.
dRash contains: dermatitis allergic, acne, erythema multiforme, rash maculopapular, rash erythematous.
eLipid disorder contains: dyslipidemia, blood cholesterol increased, low-density lipoprotein increased, hypercholesterolemia, blood triglycerides increased, hyperlipidemia.
fBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial.
Serious adverse reactions were reported in 2 (5%) patients with PNH who received FABHALTA. They included COVID-19 and bacterial pneumonia
Bacterial infectionf and nausea were reported in 2 patients each (5%). Dizziness and urticaria were reported in 1 patient each (3%)
fBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial.
No patient discontinued FABHALTA due to an adverse reaction in the 24-week core treatment period or during the 24-week extension phase of the APPOINT trial5
ADDITIONAL END POINTS
Clinical breakthrough hemolysis and MAVEs
The data from this additional analysis are exploratory; therefore, not subject to family-wise Type 1 error control, and presented for observation only. No formal conclusions can be made.
During the 24-week core treatment period, no clinical BTH¶ or MAVEs# were observed in patients on FABHALTA5
¶Clinical BTH was defined as meeting clinical criteria (either decrease of Hb level ≥2 g/dL compared with the latest assessment or within 15 days; or signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia, or any other significant clinical PNH-related signs and symptoms) and laboratory criteria (LDH >1.5 x ULN and increased as compared with the last 2 assessments).5
#The definition of MAVEs included: acute peripheral vascular occlusion, amputation, cerebrovascular accident, dermal thrombosis, gangrene, hepatic/portal vein thrombosis, mesenteric/visceral arterial or venous thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial or vein thrombosis, thrombophlebitis/deep vein thrombosis, transient ischemic attack, and unstable angina.5
**BTH and MAVEs were reported from the start of FABHALTA to Day 336.4