Express Pharma

US FDA approves Novartis’ eltrombopag

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The approval was based on two randomised, double-blinded, placebo-controlled trials enrolling paediatric patients with chronic ITP

The US Food and Drug Administration (FDA) has recently approved eltrombopag (Promacta for oral suspension, Novartis) for the treatment of thrombocytopenia in paediatric patients one year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The approval was based on two randomised, double-blinded, placebo-controlled trials enrolling paediatric patients with chronic ITP. The PETIT trial (Paediatric patients with thrombocytopenia from ITP) was a phase II trial with the primary efficacy endpoint of the proportion of subjects achieving platelet counts greater than or equal to 50 x109/L at least once between days eight and 43 of the randomised period of the study.

Patients were stratified by age cohort (12-17 years, six to11 years, and one to five years), and 67 patients were randomised (2:1) to eltrombopag or placebo for seven weeks. Eltrombopag dose was titrated to a target platelet count of 50-200 x109/L. The percentage of responders was statistically significantly higher in patients treated with eltrombopag compared to placebo (62.2 per cent vs. 31.8 per cent, p-value = 0.011).

The PETIT2 trial was a phase III trial with the primary efficacy endpoint of the proportion of subjects receiving eltrombopag, compared to placebo, who achieve platelet counts greater than or equal to 50 x109/L for at least six out of eight weeks, between weeks five to 12 of the randomised period. In the randomised period, 92 paediatric patients with chronic ITP were randomised (2:1) to eltrombopag or placebo for 13 weeks. Eltrombopag dose was titrated to a target platelet count of 50-200 x109/L. More patients in the eltrombopag group met the primary endpoint than in the placebo group (41.3 per cent vs 3.4 per cent, p-value < 0.001).

Safety data was evaluated in 107 patients who were randomised to eltrombopag during both trials. The most common adverse reactions that occurred more frequently in patients treated with eltrombopag were upper respiratory tract infection, nasopharyngitis, cough, diarrhoea, pyrexia, rhinitis, abdominal pain, oropharyngeal pain, toothache, ALT increased, rash, AST increased and rhinorrhoea.

Serious adverse reactions were reported in eight per cent of patients during the randomised part of both trials with no serious adverse event occurring in more than one patient (one per cent). An elevation of ALT greater than or equal to 3x upper limit of normal occurred in five per cent of patients in the eltrombopag group, and of those two per cent had increases in ALT greater than or equal to 5x upper limit of normal. No deaths or thromboembolic events occurred during either study.

The recommended dose and schedule for paediatric patients six years and older is 50 mg daily or 25 mg daily of the tablet formulation for patients with East Asian ancestry. The recommended dose for all patients age one to five years is 25 mg daily of the powder for oral suspension formulation.

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