APPOINT: a study of complement inhibitor–naive adults with PNH1
With FABHALTA oral monotherapy, substantial Hb improvements without the need for RBC transfusions are within reach
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PRIMARY END POINT
Patients with sustained Hb increase of ≥2 g/dL* from baseline in the absence of RBC transfusions† after the 24-week core treatment period
*Assessed between Day 126 and 168.1
†Assessed between Day 14 and 168. Requiring RBCs refers to any patient receiving transfusions or meeting protocol-defined criteria.2
‡Based on observed and central laboratory data only. Assessed at a single Week 48 (Day 336) visit. Patients who received transfusions between Day 14 and 336 or were missing Day 336 assessment were considered nonresponders.3
§Assessed at a single visit at Week 48 (Day 336).3
‖The 'n' values reflect patients who responded based on observed data.3
Higher Hb levels in the absence of RBC transfusions are within reach1
FABHALTA is the first PNH treatment to evaluate a primary end point of the response rate of patients achieving sustained Hb increase of ≥2 g/dL, as opposed to Hb stabilization4-6
Patients taking FABHALTA experienced an increase in adjusted mean Hb level of +4.29 g/dL from baseline
ADDITIONAL END POINTS
Patients experienced increases in mean Hb by Week 1, with increases through Week 242,7
Mean Hb levels (g/dL) through Week 24 (values within 30 days of transfusion excluded and are considered missing)
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.
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Sustained Hb levels of ≥12 g/dL* in the absence of RBC transfusions† after 24 weeks was observed in 47.5% of patients (n=19/40; 95% CI, 31.5-63.9)9
*Assessed between Day 126 and 168.9
†Assessed between Day 14 and 168. Requiring RBCs refers to any patient receiving transfusions or meeting protocol-defined criteria.9
RBC transfusion avoidance with FABHALTA over the 24-week treatment period
ADDITIONAL END POINT
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.
Patients achieving RBC transfusion avoidance assessed between Week 2 and 249
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In the 6 months before trial enrollment, 70% (n=28/40) of patients required a transfusion.2 Transfusion avoidance in APPOINT was defined as absence of administration of packed-RBC transfusions between Day 14 and 168.9
The impact of FABHALTA on LDH and ARC levels
ADDITIONAL END POINTS
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.
Absolute reticulocyte count (ARC) and lactate dehydrogenase (LDH) are 2 of the known biomarkers of hemolytic activity. ARC is a marker of both IVH and EVH, while LDH primarily reflects IVH.10-12
Adjusted mean change from baseline in LDH2,9,‖‖
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‖‖Mean of visits between Day 126 and 168.2
¶¶Day 7.2
##Day 14.2
***Day 168.2
Adjusted mean change from baseline in ARC2,9,‖‖
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‖‖Mean of visits between Days 126 and 168.2
With FABHALTA, the adjusted mean change from baseline in FACIT-Fatigue score was +10.8
ADDITIONAL END POINT
Patient-reported FACIT-Fatigue scores may be an underestimation or overestimation because patients were not blinded to treatment.
The data from this additional analysis are exploratory; therefore, not subject to family-wise Type 1 error control, and presented for observation only. Due to the exploratory nature, small sample size, single-arm and open-label design, no formal conclusions can be made.
Assessed between Week 18 and 24. The adjusted mean change* from baseline in FACIT-Fatigue score§§§ in patients taking FABHALTA was +10.8 (95% CI, 8.63-12.95)2,9
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In separate, large-scale surveys, the mean FACIT-Fatigue score for the general population was 4413,14,¶¶¶
*Assessed between Day 126 and 168.2
§§§The Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-Fatigue) is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. The level of fatigue is measured on a 4-point Likert scale (in the study, 4=not at all fatigued to 0=very much fatigued), with 0 being the worst possible score and 52 the best.2
‖‖‖Baseline mean FACIT-Fatigue scores and adjusted mean change in FACIT-Fatigue scores at Day 168 were reported for 40 patients.2
¶¶¶The FACIT-Fatigue score for the general population was determined through the assessment of 1010 adults in the US in 2002 and 2426 adults in Germany in 2018.13,14
