Table 38 Table: Summary of primary endpoints and secondary efficacy and QoL endpoints after the 24-week randomized treatment period of APPLY-PNH

From: The 49th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Sessions (O009-O172)

 

Endpoints

Arm

Proportion of patients

Summary statistic

Comparative statistic

Two-sided, unadjusted P value

  

n/M*

Marginal proportion

(% [95% CI])

Difference in marginal proportion

(% [95% CI])

 

Primary

Response defined as increase from baseline in Hb of ≥2 g/dL† in the absence of RBCTs‡

Iptacopan

SoC

51/60

0/35

82.3 (73.4, 90.2)

2.0 (1.1, 4.1)

80.3

(71.3, 87.6)

<0.0001

Response defined as Hb level ≥12 g/dL† in the absence of RBCTs‡

Iptacopan

SoC

42/60

0/35

68.8 (58.3, 78.9)

1.8 (0.9, 4.0)

67.0

(56.3, 76.9)

<0.0001

Secondary

Transfusion avoidance‡

Iptacopan

SoC

60/62

14/35

96.4 (90.7, 100.0)§

26.1 (12.4, 42.7)§

70.3

(52.6, 84.9)§

<0.0001§

  

M/N‖

Adjusted mean change from baseline (95% CI)

Adjusted mean difference in change from baseline (95% CI)

 

Change from baseline in Hb (g/dL)†,¶

Iptacopan

SoC

62/62

30/35

+3.59 (3.32, 3.86)

−0.04 (−0.42, 0.35)

+3.63

(3.18, 4.08)

<0.0001

Change from baseline in FACIT-F score†,**

Iptacopan

SoC

62/62

31/33

+8.59 (6.72, 10.47) + 0.31 (−2.20, 2.81)

+8.29

(5.28, 11.29)

<0.0001

Change from baseline in ARC (109/L)†,††

Iptacopan

SoC

62/62

35/35

−115.89 (−126.49, −105.30) + 0.37 (−13.03, 13.77)

−116.26

(−132.17, −100.36)

<0.0001

  

M/N‖

Geometric adjusted mean ratio to baseline

Reduction

(% [95% CI])

 

Ratio to baseline in log-transformed LDH (U/L)†,‡‡

Iptacopan

SoC

62/62

35/35

0.96 (0.90, 1.03)

0.98 (0.89, 1.07)

1.15

(−10.18, 11.32)

No superiority

  

n/N§§

Adjusted annual rate

(% [95% CI])

Rate ratio

(95% CI)

 

Rate of clinical breakthrough hemolysis‖‖

Iptacopan

SoC

2/62

6/35

0.07 (0.02, 0.31)

0.67 (0.26, 1.72)

0.10

(0.02, 0.61)

0.0118

Rate of MAVEs

Iptacopan

SoC

1/62

0/35

0.03 (0.00, 0.25)

0

Not estimable

No superiority

  1. *n=number of patients with response, M=number of patients with evaluable/non-missing data; †Assessed between D126–168; ‡Between D14–168; §The prespecified methodology for handling of missing data may have underestimated transfusion avoidance in the SoC arm, so a post hoc sensitivity analysis was conducted using a different approach. In this analysis, marginal proportions (95% CI) were 96.7% (91.3, 100.0) vs. 38.9% (23.1, 55.8) for iptacopan and SoC, respectively (P<0.0001); ‖M=number of patients with evaluable/non-missing data, N=overall number of patients; ¶Excluding values within 30 days of RBCT. Mean (SD) baseline Hb levels were 8.93 (0.70) and 8.85 (0.90) g/dL in the iptacopan and SoC arms, respectively; **Mean (SD) baseline FACIT-F scores were 34.7 (9.8) and 30.8 (11.5) in the iptacopan and SoC arms, respectively; ††Mean (SD) baseline ARCs were 193.2 (83.6) and 190.6 (80.9) x 109/L in the iptacopan and SoC arms, respectively; ‡‡Mean (SD) baseline LDH levels were 269.1 (70.1) and 272.7 (84.8) U/L in the iptacopan and SoC arms, respectively; §§n=number of patients with at least one event, N=overall number of patients; ‖‖Events that met the protocol-specified criteria for clinical breakthrough hemolysis
  2. ARC, absolute reticulocyte count; CI, confidence interval; D, day; Hb, hemoglobin; FACIT-F, Functional Assessment of Chronic Illness Therapy – Fatigue; LDH, lactate dehydrogenase; MAVE, major adverse vascular event; QoL, quality of life; RBCT, red blood cell transfusion; SD, standard deviation; SoC, standard of care
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