Novartis announced the FDA’s acceptance of their supplemental New Drug Application (sNDA) and granted Priority Review designation to Promacta (eltrombopag) in combination with standard immunosuppressive therapy (IST) for first-line treatment of severe aplastic anemia (SAA).
Promacta, which is marketed as Revolade in most countries outside the US, is an oral thrombopoietin receptor agonist (TPO-RA) that is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST. It is also approved for adults and children with chronic immune thrombocytopenia (ITP) for patients who are refractory to other treatments and for the treatment of thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection.
The Priority Review for first-line SAA is based on Novartis’ analysis of research sponsored by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and conducted under a Cooperative Research and Development Agreement (CRADA).
The study showed that more than half (52 percent) of treatment-naïve SAA patients achieved complete response at six months when treated with Promacta concurrently with standard IST, which was an increase of 35 percent compared to those treated with the standard IST alone1. The overall response rate was 85 percent at six months2.
Severe aplastic anemia is a rare, life-threatening, acquired blood disorder in which a patient’s bone marrow fails to produce enough red blood cells, white blood cells and platelets3. As a result, people living with this serious disease may experience debilitating symptoms and complications, such as fatigue, trouble breathing, recurring infections and abnormal bruising or bleeding that can limit their daily activities4.
Historically, SAA was nearly uniformly a fatal diagnosis due to infection or hemorrhage resulting from prolonged pancytopenia; untreated SAA can result in 80-90 percent mortality in one to two years5. The prevalence rates vary for aplastic anemia in the US, but it is believed that 500-1,000 new cases are diagnosed each year6. The standard treatment regimen for individuals unable to receive or not eligible candidates for hematopoietic stem cell transplantation (HSCT) in the US for treatment-naïve SAA is IST. With IST as first-line treatment, up to one-third of patients and approximately 40 percent of those unresponsive to IST die within 5 years of diagnosis7.
According to FDA guidelines, treatments that receive Priority Review designation are those that address a serious or life threatening disease or condition and, if approved, would provide a significant improvement in treatment safety or efficacy. If a treatment is granted Priority Review designation, the goal of the FDA is to issue a decision within six months of application submission, rather than ten months for standard review.
References
- Townsley DM et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med 2017 Apr 20; 376:1540.
- Novartis Data on File.
- National Heart, Lung and Blood Institute (2018). Aplastic Anemia. Available at: https://www.nhlbi.nih.gov/node/80148. Accessed January 18, 2018.
- Townsley DM, Desmond R, Dunbar CE, et al. Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes. Int J Hematology. 2013;98(1):48-55.
- Rosenfeld S et al. Antithymocyte globulin and cyclosporine for severe aplastic anemia: Association between hematologic response and long-term outcome. JAMA. 2003;289(9):1130–1135. doi:10.1001/jama.289.9.1130.
- National Organization for Rare Diseases (2018). Acquired Aplastic Anemia. Available at: https://rarediseases.org/rare-diseases/acquired-aplastic-anemia/. Accessed March 26, 2018.
- Valdez JM, Scheinberg P, Nunez O, et al. Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clin Infect Dis. 2011; 52(6):726-735.
(Source: Novartis Pharmaceutical Corporation)
Filed Under: Drug Discovery
