Abstract: SA-PO247
Potential Safety Concern of Daprodustat Compared with Injectable Erythropoiesis-Stimulating Agents in Patients with Anemia on Hemodialysis and Not on Dialysis: A Pooled Analysis
Session Information
- Anemia and Iron Metabolism: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 202 Anemia and Iron Metabolism: Clinical
Authors
- Hamano, Takayuki, Osaka University Graduate School of Medicine, Suita, Osaka-Fu, Japan
- Nangaku, Masaomi, the University of Tokyo School of Medicine, Tokyo, Japan
- Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan
- Tsubakihara, Yoshiharu, Graduate School of Health Care Science, Jikei Institute, Yodogawa-ku, Osaka, Japan
- Nagakubo, Takashi, GlaxoSmithKline, Tokyo, Japan
- Yonekawa, Taeko, GlaxoSmithKline, Tokyo, Japan
- Kimura, Toshifumi, GlaxoSmithKline, Tokyo, Japan
- Endo, Yukihiro, GlaxoSmithKline, Tokyo, Japan
- Cobitz, Alexander Ralph, GlaxoSmithKline, Tokyo, Japan
Background
Daprodustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor under development for treating anemia in hemodialysis (HD) and non-dialysis (ND) patients. Safety analyses were performed to evaluate potential safety concerns such as ocular, cardiovascular, and cancer related adverse events (AEs).
Methods
Post-hoc pooled analyses were conducted by using 2 open-label, randomized controlled trials (RCTs) compared to injectable erythropoiesis stimulating agent (ESA) in ND patients (ClinicalTrials.gov Identifier: NCT01977573, NCT02791763) and one open-label and one double-blind, RCTs compared to ESA in HD patients (NCT01977482, NCT02969655). The principal outcomes were frequencies of a subset of the predefined AEs of special interest (AESIs): ocular (proliferative retinopathy, macular edema, choroidal neovascularization), cardiovascular (all-cause death, myocardial infarction, stroke, heart failure, thromboembolic events, thrombosis of vascular access) and cancer (cancer-related mortality and tumor progression and recurrence) related AEs, and ophthalmological findings by ophthalmologists during treatment.
Results
AEs in each AESI category were pooled from 549 patients (n=319; daprodustat, n=230; ESA) and 487 patients (n=313, n=174) in ND and HD patients, respectively. Median exposure (days, daprodustat vs. ESA) in ND and HD patients was 172 vs. 337 and 169 vs. 365, respectively. In ND patients, the incidence (daprodustat vs. ESA) of ocular, cardiovascular, and cancer related AEs were 3% vs. 3%, 3% vs. 6% and 1% vs. 1%, respectively. In HD patients, these were respectively 2% vs. 2%, 7% vs. 7% and <1% vs. <1%. The incidence of ophthalmological findings were 11% vs. 10% in ND patients and 6% vs. 8% in HD patients. There was no meaningful difference in the frequencies of these predefined AESIs and ophthalmological findings between the treatment groups in ND and HD patients.
Conclusion
Daprodustat showed no new safety concerns in these predefined AESIs in these clinical studies, but further investigation will be needed.
Funding
- Commercial Support – GlaxoSmithKline