FDA Grants Priority Review to Eltrombopag for Frontline Use in Severe Aplastic Anemia
The FDA has granted a priority review to the oral thrombopoietin-receptor agonist eltrombopag (Promacta) in combination with standard immunosuppressive therapy as a frontline treatment for severe aplastic anemia.
The FDA has granted a priority review to the oral thrombopoietin-receptor agonist eltrombopag (Promacta) in combination with standard immunosuppressive therapy as a frontline treatment for severe aplastic anemia (SAA).
Under the priority designation, the FDA will review the drug’s supplemental new drug application within 6 months from the acceptance of the filing, compared with the standard 10 months.
The designation is based on a Novartis analysis of results from research conducted by the National Heart, Lung and Blood Institute of the National Institutes of Health. When administered concurrently with standard immunosuppressive treatment, eltrombopag was associated with a 52% complete response (CR) rate at 6 months in treatment-naïve patients with SAA. The 6-month overall response rate (ORR) was 85%.
"Promacta is a great example of our drive to develop innovative treatments in serious disease areas where few treatment options exist," Samit Hirawat, MD, head, Novartis Oncology Global Drug Development, said in a statement.
In April 2017, results were published in the New England Journal of Medicine from a pivotal phase I/II trial of frontline eltrombopag plus immunosuppressive therapy in 92 patients with SAA. Three consecutively enrolled cohorts differed in starting time and duration of eltrombopag. The median patient age was 32 years (range, 3-82). There were 50 male patients and 42 female patients.
Patients in cohort 1 (n = 30) received eltrombopag from day 14 to 6 months and those in cohort 2 (n = 31) received the treatment from day 14 to 3 months. The longest duration of exposure to eltrombopag was in cohort 3 (n = 31), in which patients received the treatment from day 1 to 6 months.
Complete hematologic response at 6 months was the primary outcome measure. Among the secondary outcome measures were ORR and overall survival.
The efficacy was greatest in cohort 3, in which patients had the longest exposure to eltrombopag. The CR rate at 6 months was 58% in this cohort, compared to 26% in cohort 2, and 33% in cohort 1. The ORRs at 6 months were 94%, 87%, and 80%, respectively. Across the entire study, the survival rate at 2 years was 97%.
Across the overall 92-patient population, treatment-related grade ≥3 adverse events (AEs) or serious AEs included maculopapular rash (n = 2), pruritus (n = 1), abdominal pain (n = 2), and liver test abnormalities (n = 18).
“The addition of eltrombopag to immunosuppressive therapy was associated with markedly higher rates of hematologic response among patients with severe aplastic anemia than in a historical cohort,” lead author Danielle M. Townsley, MD, and coauthors wrote in their conclusion.
Eltrombopag is currently approved for the treatment of patients with SAA who have an insufficient response to immunosuppressive therapy. It is also approved for the treatment of thrombocytopenia in adult and pediatric patients aged ≥1 year with chronic immune (idiopathic) thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Townsley DM, Scheinberg P, Winkler T, et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med. 2017;376(16):1540-1550. doi: 10.1056/NEJMoa1613878