PRIMARY END POINTS

Significantly more patients achieved Hb improvements in the absence of RBC transfusions with FABHALTA vs C5is¹

Patients with Hb increase of ≥2 g/dL* from baseline in the absence of RBC transfusions^† after 24 weeks

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*Assessed between Days 126 and 168.^{1       
†}Assessed between Days 14 and 168. Requiring RBCs refers to any patient receiving transfusions or meeting protocol-defined criteria.^{2      
‡}Adjusted difference in proportion.¹ 

Patients with normalized^§ Hb of ≥12 g/dL* in the absence of RBC transfusions^† after 24 weeks

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*Assessed between Days 126 and 168.^{1       
†}Assessed between Days 14 and 168. Requiring RBCs refers to any patient receiving transfusions or meeting protocol-defined criteria.^{2       
‡}Adjusted difference in proportion.^{1     
§}Normalization defined as meeting the primary end point of Hb ≥12 g/dL.² Normal Hb levels vary, but generally are between 12-16 g/dL for women and 13-18 g/dL for men.³

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 stabilization^1,4-6

ADDITIONAL END POINT

FABHALTA delivered a +3.6 g/dL adjusted mean change in Hb level vs -0.1 with C5is¹

Mean Hb levels (g/dL) through Week 24 (values within 30 days of transfusion were excluded and considered missing)⁷

The data in the figure below is exploratory, presented for observation only. No formal conclusions or comparisons between the two treatment arms can be made.

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*Assessed between Days 126 and 168.¹         

ADDITIONAL END POINT

RBC transfusion avoidance assessed between Weeks 2 and 24^1,‖,¶

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• 35/62 patients in the FABHALTA arm and 21/35 in the C5is arm had at least 1 RBC transfusion in the 6 months prior to trial enrollment²

^‡Adjusted difference in proportion.^1   
‖Assessed between Days 14 and 168.^{1     
¶}Transfusion avoidance is defined as absence of administration of packed-RBC transfusions between Days 14 and 168.¹     
 

ADDITIONAL END POINTS

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.^8-10

FABHALTA delivered greater reductions in ARC vs C5is¹

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Adjusted mean change from baseline in ARC (10⁹/L) assessed between Weeks 18 and 24*         
Values include post-transfusion data.⁷

*Assessed between Days 126 and 168.^1,7   

No statistically significant difference in LDH was seen between FABHALTA and C5is^1,7

The data from this additional analysis are descriptive in nature, presented for observation only. No formal conclusions or comparisons between the two treatment arms can be made.

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Adjusted geometric mean ratio to baseline in LDH assessed between Weeks 18 and 24*         

In both the FABHALTA- and C5i-treated groups, the mean (SD) (FABHALTA: 275.2 U/L [117.6]; C5is: 280.7 U/L [128.2]) and median (range) (FABHALTA: 251 U/L [150-859]; C5is: 242 U/L [142-815]) LDH values at Day 168 of the randomized treatment period were <1.5 x ULN.⁷ 

*Assessed between Days 126 and 168.^1,7    

With FABHALTA, the adjusted mean change from baseline in FACIT-Fatigue score was +8.6 and +0.3 with C5is

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 descriptive in nature, presented for observation only. At baseline, ~50% of participants reported the least severe response categories (“not at all” and “a little bit”) for the 10/13 questions in the FACIT-Fatigue scale. Due to the small sample size, open-label design, and the low level of fatigue reported at baseline, no formal conclusions or comparisons between the two treatment arms can be made.

• During the 24-week randomized treatment period, the adjusted mean change from baseline in FACIT-Fatigue score^# was +8.6 in patients taking FABHALTA and +0.3 with C5is (difference: 8.34; 95% CI, 5.26-11.41)⁷

• The adjusted mean* was assessed between Weeks 18 and 24. Values within 30 days after transfusion were included in the analysis⁷

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• In separate large-scale surveys, the mean FACIT-Fatigue score for the general population was 44^11,12,††

*Assessed between Days 126 and 168.^1,7 
#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 (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 were reported for 62 patients in the FABHALTA arm and 33 patients in the C5is arm.⁷ At Day 168, the adjusted mean change in FACIT-Fatigue score was reported for 62 patients in the FABHALTA arm and 31 patients in the C5is arm.^{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.^11,12