GlaxoSmithKline plc (GSK) announced today that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for the once-daily use of Promacta® (eltrombopag) in patients with severe aplastic anaemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).
SAA is a blood disorder where the bone marrow fails to make enough red blood cells, white blood cells, and platelets. Eltrombopag, an oral thrombopoietin (TPO) receptor agonist, works by helping to induce proliferation and differentiation of bone marrow stem cells to increase production of blood cells.
“FDA approval of Promacta addresses a significant treatment need for this very rare but serious blood disorder in those who have failed current treatment options,” said Dr. Paolo Paoletti, President of Oncology, GSK. “Through collaboration with the National Institutes of Health, whose studies demonstrate the potential for Promacta to achieve a haematologic response in at least one lineage — red blood cells, platelets, or white blood cells — patients now have a treatment option where one didn’t previously exist.”
Promacta gained Breakthrough Therapy designation status from the FDA in January 2014 and Priority Review in April 2014. Today’s approval by the FDA is based on results from an investigator-sponsored Phase II study (09-H-0154) conducted by the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH). The study demonstrated a haematologic response in SAA patients treated with eltrombopag who had an insufficient response to IST:
- Forty per cent (95% CI, 25, 56) of patients (N=17) experienced a haematologic response in at least one lineage – platelets, red blood cells (RBC), or white blood cells (ANC) – after Week 12.
- In the extension phase, eight patients achieved a multi-lineage response; four of these patients subsequently tapered off treatment and maintained the response (median follow up 8.1 months, range 7.2-10.6 months).
- Ninety-one per cent of patients were platelet transfusion-dependent at baseline; the platelet transfusion-free period in responders ranged from eight to 1,096 days (median 200 days).
- Eighty-six per cent of patients were RBC-transfusion dependent at baseline; the RBC transfusion-free period in responders ranged from 15 to 1,082 days (median 208 days).
The most common adverse reactions (≥20%) in the single-arm, open-label trial, in 43 patients with SAA who received Promacta were: nausea (33%), fatigue (28%), cough (23%), diarrhoea (21%), and headache (21%). In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality reported, including five patients who had complex changes in chromosome 7. If new cytogenetic abnormalities are observed, discontinuation of Promacta should