FDA Grants Frontline Eltrombopag Priority Review for Severe Aplastic Anemia

Samit Hirawat

The FDA has granted a priority review to a supplemental new drug application (sNDA) for eltrombopag (Promacta) for use in combination with standard immunosuppressive therapy as a frontline treatment for patients with severe aplastic anemia (SAA), according to Novartis, the manufacturer of the oral thrombopoietin-receptor agonist.

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. The analysis found that eltrombopag, administered concurrently with standard immunosuppressive treatment, 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%.

Under the priority designation, the FDA will review the sNDA within 6 months from the acceptance of the filing, compared with the standard 10 months.

"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.

"Thanks to the many individuals and organizations who have helped us to advance the development of this promising medicine. We will continue our work with the FDA to make Promacta available for this potential new indication as quickly as possible,” added Hirawat.

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 patients with SAA. The study included 92 patients in 3 consecutively enrolled cohorts that differed in the 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