FDA Approves Frontline Eltrombopag for Severe Aplastic Anemia

The FDA has expanded the approval of eltrombopag in combination with standard immunosuppressive therapy to include newly diagnosed adult and pediatric patients 2 years and older with severe aplastic anemia.

The FDA has expanded the approval of eltrombopag (Promacta) in combination with standard immunosuppressive therapy (IST) to include newly diagnosed adult and pediatric patients 2 years and older with severe aplastic anemia (SAA), according to Novartis, the manufacturer of eltrombopag.1 The agency also granted the agent a breakthrough therapy designation as a counter measure for hematopoietic sub-syndrome of acute radiation syndrome (H-ARS).

The approval is based on a Novartis analysis sponsored by the National Heart, Lung, and Blood Institute (NHLBI) Division of Intramural Research Program and conducted under a Cooperative Research and Development Agreement. Findings showed that treatment with eltrombopag given concurrently with standard IST led to an overall response rate (ORR) at 6 months of 79% (95% CI, 69%-87%). Forty-four percent of definitive IST-naïve patients achieved a complete response (CR) at 6 months when treated with concurrent eltrombopag; this was 27% higher than the historically observed CR rate with standard IST alone (17%).

"Patients with SAA sometimes do not respond to the current treatment standard of IST," said Phillip Scheinberg, MD, head, Division of Hematology, Hospital A Beneficência Portuguesa de São Paulo in Brazil, and previously with the NHLBI. "With this approval, physicians now have an option to add Promacta to the standard IST in a regimen that has demonstrated significant overall and complete response rates upfront in SAA and reduce the numbers of those who are unresponsive to initial therapy."

Eltrombopag is an oral thrombopoietin receptor agonist with a prior indication for patients with SAA who have had an insufficient response to standard therapy, for adults and pediatric patients with chronic immune thrombocytopenia who are refractory to other therapies, and for the treatment of thrombocytopenia in patients with chronic hepatitis C virus infection.

Additional updated data showed that the median duration of response was 24.3 months for patients treated with eltrombopag for 6 months in combination with horse anti-thymocyte globulin and cyclosporine (CsA) followed by maintenance CsA4.

In April 2017, data were published in the New England Journal of Medicine from a phase I/II trial of frontline eltrombopag plus IST in patients with SAA.2 The study included 92 patients in 3 consecutively enrolled cohorts that varied in the starting time and duration of eltrombopag. The median age was 32 years (range, 3-82); there were 50 males and 42 females.

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 agent from day 1 to 6 months.

The primary endpoint was complete hematologic response at 6 months; secondary endpoints were ORR and overall survival.

Cohort 3 showed the most clinical activity as patients had the longest exposure to eltrombopag. The CR rate at 6 months was 58% in this cohort, versus 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).

Novartis also submitted a Type II variation application for eltrombopag as a frontline therapy for patients with SAA to the European Medicines Agency in 2018; a decision is expected to made in 2019, the company stated in the release.

"Severe aplastic anemia can be a fatal diagnosis if left untreated, and many patients fail to respond to current initial treatment options," said Liz Barrett, CEO of Novartis Oncology, in a news release. "Today's US approval for Promacta is an important step forward for people living with this challenging disease and shows how Novartis continues to reimagine care in areas where few treatment options exist."

Regarding the breakthrough therapy designation, research and development of eltrombopag for H-ARS is being conducted under contract with the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority as potential use following radio/nuclear threats, specifically to treat patients exposed to myelosuppressive doses of radiation. Eltrombopag has been shown to decrease the risk of hemorrhage in patients with H-ARS, Novartis stated.


  1. FDA Approves Novartis Drug Promacta for First-Line SAA and Grants Breakthrough Therapy Designation for Additional New Indication. Novartis. Published November 16, 2018. https://on.mktw.net/2TeGwse. Accessed November 16, 2018.
  2. 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.