TEAEs of patients with SCD treated with mitapivat (n = 10): safety analysis set of the 8-week dose-finding period and 1-year fixed-dose extension period
| . | Grade 1 . | Grade 2 . | Grade 3 . | Grade 4 . | Grade 5 . |
|---|---|---|---|---|---|
| Total | 34 (77%) | 8 (18%) | 0 (0%) | 1 (2%)∗ | 1 (2%)† |
| Alanine aminotransferase increased | 7 (70%) | ||||
| Aspartate aminotransferase increased | 6 (60%)‡ | ||||
| Headache | 3 (30%) | 1 (10%) | |||
| Dyspepsia | 2 (20%) | ||||
| Abdominal pain | 2 (20%) | ||||
| Insomnia | 2 (20%) | ||||
| Diarrhea | 2 (20%) | ||||
| SCD low-grade pain events§ | 1 (10%) | 1 (10%) | |||
| Lymphocyte count increased | 2 (20%) | ||||
| Influenza-like symptoms | 1 (10%) | ||||
| Vaccination site lymphadenopathy | 1 (10%) | ||||
| Rhinorrhea | 1 (10%) | ||||
| Testosterone (total/free) increased | 1 (10%) | ||||
| Palpitations | 1 (10%) | ||||
| Hearing impaired | 1 (10%) | ||||
| Dysesthesia | 1 (10%) | ||||
| Iron deficiency | 1 (10%) | ||||
| Bloating | 1 (10%) | ||||
| Lung infection | 1 (10%) | ||||
| Pruritus | 1 (10%) | ||||
| Hemolysis | 1 (10%) | ||||
| Gastritis | 1 (10%) | ||||
| Urinary tract infection | 1 (10%)∗ | ||||
| Pulmonary embolism due to COVID-19 | 1 (10%)† |
| . | Grade 1 . | Grade 2 . | Grade 3 . | Grade 4 . | Grade 5 . |
|---|---|---|---|---|---|
| Total | 34 (77%) | 8 (18%) | 0 (0%) | 1 (2%)∗ | 1 (2%)† |
| Alanine aminotransferase increased | 7 (70%) | ||||
| Aspartate aminotransferase increased | 6 (60%)‡ | ||||
| Headache | 3 (30%) | 1 (10%) | |||
| Dyspepsia | 2 (20%) | ||||
| Abdominal pain | 2 (20%) | ||||
| Insomnia | 2 (20%) | ||||
| Diarrhea | 2 (20%) | ||||
| SCD low-grade pain events§ | 1 (10%) | 1 (10%) | |||
| Lymphocyte count increased | 2 (20%) | ||||
| Influenza-like symptoms | 1 (10%) | ||||
| Vaccination site lymphadenopathy | 1 (10%) | ||||
| Rhinorrhea | 1 (10%) | ||||
| Testosterone (total/free) increased | 1 (10%) | ||||
| Palpitations | 1 (10%) | ||||
| Hearing impaired | 1 (10%) | ||||
| Dysesthesia | 1 (10%) | ||||
| Iron deficiency | 1 (10%) | ||||
| Bloating | 1 (10%) | ||||
| Lung infection | 1 (10%) | ||||
| Pruritus | 1 (10%) | ||||
| Hemolysis | 1 (10%) | ||||
| Gastritis | 1 (10%) | ||||
| Urinary tract infection | 1 (10%)∗ | ||||
| Pulmonary embolism due to COVID-19 | 1 (10%)† |
Data are n (%). Patients with multiple AEs within a preferred term were counted only once in that preferred term. For participants with multiple occurrences of an AE, the AE with the worst Common Terminology Criteria for Adverse Events grade is included in the summary.
Grade 4 TEAE was a SAE, assessed as nontreatment-related, in a noncompliant patient with an urinary tract infection, requiring intensive care unit admission for 1 night.
Grade 5 TEAE was a SAE, assessed as nontreatment-related, in a patient with a massive pulmonary embolism due to COVID-19.
One patient had an aspartate aminotransferase increase grade 1 after an elective cholecystectomy. Mitapivat dosage was reduced from 100 mg twice daily to 50 mg twice daily, and the level normalized at the following visit.
SCD low-grade pain events are not meeting the protocol definition of a VOEs. According to the study protocol, VOEs were not reported as (serious) AE unless a VOE was atypical for the patient either in severity or presentation.