Page 173 - 2021_12-Haematologica-web

Danicopan, an oral factor D inhibitor for PNH
nificant reductions of LDH at day 28 (primary endpoint) and throughout treatment duration. In contrast with stan- dard C5 inhibitor therapies, the inhibition of intravascular hemolysis observed during danicopan treatment was not associated with persistently increased bilirubin and reticu- locyte count, or with the emergence of C3 deposition on surviving GPI-deficient erythrocytes, in agreement with its anticipated effect on extravascular hemolysis. Concomitant inhibition of intravascular hemolysis and prevention of C3-mediated extravascular hemolysis
resulted in improvement of anemia, with a mean hemo- globin gain of 1.7 g/dL after 12 weeks of treatment. Consistent with these findings, all patients exhibited sig- nificant increases in the percentage of GPI-deficient ery- throcytes, confirming the extended half-life of these cells in vivo. Furthermore, all patients had improvements in FACIT-Fatigue quality-of-life measurements; FACIT- Fatigue scores were used in this proof-of-concept study due to the lack of validated instruments for patient-report- ed outcomes in PNH. Additional patient-reported out-
Standard severity grade
Table 2. Adverse events.
Primary system organ class preferred term*
Number of subjects reporting Number of unique TEAE†
Number of subjects with SAE
Blood and lymphatic system disorders
Hemolysis Gastrointestinal disorders
Abdominal pain Mouth ulceration Nausea
Vomiting
General disorders and administration site conditions Fatigue
Non-cardiac chest pain
Edema, peripheral
Vaccination site erythema Infections and infestations
Pharyngitis
Upper respiratory tract infection Viral upper respiratory tract infection
Injury, poisoning, and procedural complications Contusion
Investigations
Alanine aminotransferase increased Aspartate aminotransferase increased
Metabolism and nutrition disorders Iron deficiency
Musculoskeletal and connective tissue disorders Back pain
Myalgia
Nervous system disorders Headache
Psychiatric disorders Irritability
Renal and urinary disorders Hemoglobinuria
Paroxysmal nocturnal hemoglobinuria
Reproductive system and breast disorders Dysmenorrhea
Skin and subcutaneous tissue disorders Rash, papular
N % of total (N=10) Mild Moderate
9 90 8 1 38 NA
1 10 - - 2 20 - - 2 20 1- 3 30 - - 1 10 - 1 1 10 1 - 1 10 1 - 1 10 1 - 4 40 - - 1 10 1 - 1 10 1 - 1 10 1 - 1 10 1 - 5 50 - - 1 10 - 1 4 40 3 1 1 10 1 - 1 10 - - 1 10 1-
Severe Life-threatening
- -
1 - - - 1 -
- -
- -
- -
- -
- -
- -
- -
.. -
- -
- -
- -
- -
- -
- -
- -
- -
1 10 - 1 10 - 1 10 - 1 10 - 1 10 1 3 30 - 2 20 2 1 10 1 4 40 - 4 40 4 1 10 - 1 10 1 3 10 - 2 20 2 1 10 - 1 10 - 1 10 1 1 10 - 1 10 1
- - -
- 1 -
- - 1
- - -
- - -
- - -
- - -
- - -
- - -
- - -
- - -
- - -
- - -
- - -
1 - -
- - -
- - -
- - -
- - -
*MedDRA Version 18.1. †This row represents the number of events; all other rows represent the number of subjects. TEAE: treatment-emergent adverse events; NA: not available; SAE: serious adverse events.
haematologica | 2021; 106(12)
3193