The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the thrombopoietin receptor agonist eltrombopag (Promacta/Revolade) to treat patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).
Eltrombopag is not approved in this setting anywhere in the world, and there are no approved therapies for SAA patients who are unresponsive to initial IST.
Of those patients who are unresponsive to initial IST, approximately 40% die from infection or bleeding within 5 years of their diagnosis.
Breakthrough therapy designation is the newest of the FDA’s programs aimed at accelerating the development and review of drugs for serious or life-threatening conditions. A drug receives the designation when preliminary clinical evidence suggests it may offer substantial improvement over available therapies on at least one clinically significant endpoint.
Eltrombopag was granted breakthrough designation based on results from an open-label, phase 2 study in 43 heavily pretreated SAA patients with an insufficient response to IST. Updated results of this trial were published in December (Desmond et al, Blood 2013).
Patients received varying doses of eltrombopag to improve blood counts. At 3 to 4 months of follow-up, the overall response rate was 40% (17/43), which included 1 tri-lineage and 5 bi-lineage responses.
Most of the 17 patients who remained on eltrombopag in an extension study continued to show improvement, but 3 lost their response. Ultimately, 7 patients had significant increases in neutrophil, red cell, and platelet counts.
Five patients who experienced robust near-normalization of blood counts discontinued the drug and maintained stable counts a median of 13 months after discontinuation (range, 1-15).
Eight patients, including 2 who responded, developed new cytogenetic abnormalities while on eltrombopag. But none have evolved to acute myeloid leukemia to date.
The only dose-limiting toxicity was reversible transaminitis. Two patients had reversible transaminitis related to treatment, and both required dose interruption.
There were no thrombotic events while patients were on treatment, but 1 responding patient developed deep-vein thrombosis 14 months after treatment discontinuation.
