Phase 3, open-label, active comparator–controlled study^1-3

Click on image to enlarge.

^*Randomization was stratified based on prior C5i treatment and transfusion history within the last 6 months.¹

PRIMARY END POINTS: RANDOMIZED TREATMENT PERIOD¹

• Proportion of patients achieving sustained Hb increase of ≥2 g/dL^† from baseline without a need for RBC transfusions^‡ after 24 weeks

• Proportion of patients achieving sustained Hb level of ≥12 g/dL^† without a need for RBC transfusions after 24 weeks^‡

ADDITIONAL END POINTS: RANDOMIZED TREATMENT PERIOD^1,2

• RBC transfusion avoidance^§ 

• Change from baseline^† in:
     - Hb levels (g/dL)^‖
     - FACIT-Fatigue scores
     - Absolute reticulocyte count (ARC) (10⁹/L)
     - Lactate dehydrogenase (LDH) level

• Occurrence of major adverse vascular events (MAVEs)^¶

• Occurrence of clinical breakthrough hemolysis (BTH)^¶,#

• Safety^¶

In the APPLY study analysis:

• All end points were based on central laboratory data^3,4

• 95% CIs for end points in the randomized treatment period were based on the Sato variance estimator⁴

• 95% CIs in the extension period were based on the Clopper-Pearson method³

^†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.^2,5
§Transfusion avoidance is defined as absence of administration of packed-RBC transfusions between Days 14 and 168.^1,4
IIExcludes values within 30 days post-transfusion in the randomized period.^1
¶Throughout the study.^2,3,6
#As per the protocol definition.^2,5
 

^¶Throughout the study.^2,3,6 
**No multiple imputation framework used for the analyses.^3 
††Excluding values within 30 days of RBC transfusion.^3 
‡‡Transfusion avoidance defined as patients who did not receive any transfusions between Days 14 and 336. Analysis considered patients who received transfusion between Days 14 and 336 after the start of FABHALTA treatment and with missing Day 336 assessment as nonresponders.³

Select baseline characteristics^1,2:

(Baseline disease characteristics were generally well balanced between treatment groups.)

Phase 3, single-arm, open-label, uncontrolled study^1,3,5

Click on image to enlarge.

^§§Confirmed by 2 measurements 2 to 8 weeks apart for patients not receiving an RBC transfusion during screening, or by 1 measurement during the first screening visit for patients receiving an RBC transfusion.^5
||||Confirmed by at least 2 measurements 2 to 8 weeks apart during the screening period.⁵

PRIMARY END POINT: CORE TREATMENT PERIOD¹

• Proportion of patients achieving sustained Hb increase of ≥2 g/dL^† from baseline without a need for RBC transfusions^‡ after 24 weeks

ADDITIONAL END POINTS: CORE TREATMENT PERIOD⁵

• Proportion of patients with sustained Hb level of ≥12 g/dL^† without a need for RBC transfusions^‡

• RBC transfusion avoidance^¶¶

• Change from baseline^† in:
     - Hb levels (g/dL)^‖
     - FACIT-Fatigue scores
     - ARC (10⁹/L)
     - LDH level

• Occurrence of MAVEs^¶

• Occurrence of clinical BTH^¶,#

• Safety^¶
  
   In the APPOINT study analysis:

• All additional end points were exploratory^1,4
• Unless otherwise noted, all end points were based on central lab data^1,4
• 95% CIs were based on the Clopper-Pearson method^3,4

^†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.^2,5 
IIExcludes values within 30 days post-transfusion in the randomized period.^1 
¶Throughout the study.^2,3,6 
#As per the protocol definition.^2,5 
¶¶Transfusion avoidance is defined as absence of administration of packed-RBC transfusions between Days 14 and end of study period.^1,4

 ^¶Throughout the study.^2,3,6 
##Based on observed and central laboratory data assessed at a single Week 36 (Day 336) visit. Patients who received transfusions between Days 14 and 336 or were missing a Day 336 assessment were considered nonresponders.³ 
***Based on observed data. Analysis considered patients who received transfusion between Days 14 and 336 as failures.^3
†††Adjusted mean assessed at a single Week 48 visit.^{3 
‡‡‡}Hb data during the core treatment period and within 30 days post-transfusion were considered missing.³

Select baseline characteristics^1,5: