Photo by Logan Tuttle
The European Commission (EC) has approved eltrombopag (Revolade), a once-daily oral thrombopoietin receptor agonist, to treat pediatric patients (age 1 and older) with chronic immune thrombocytopenia (ITP) that is refractory to other therapies.
This approval includes the use of tablets and a new oral suspension formulation of eltrombopag, which is designed for younger children who may not be able to swallow tablets.
The approval applies to all 28 member states of the European Union plus Iceland, Norway, and Liechtenstein.
Eltrombopag was previously approved by the EC for use in adults with refractory chronic ITP. The drug is also approved in the EC to treat adults with severe aplastic anemia and adults with chronic hepatitis C virus infection who have thrombocytopenia.
Eltrombopag is made by Novartis. For more details on the drug, see the full Summary of Product Characteristics, available on the European Medicines Agency’s website.
The EC’s latest approval of eltrombopag was based on data from 2 double-blind, placebo-controlled trials—the phase 2 PETIT trial and the phase 3 PETIT2 trial.
PETIT trials: Efficacy
The PETIT trial included 67 ITP patients stratified by age cohort (12-17 years, 6-11 years, and 1-5 years). They were randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The PETIT2 trial enrolled 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%—compared to 3.4% of patients in the placebo arm (P<0.001).
PETIT trials: Safety
For both trials, there were 107 eltrombopag-treated patients evaluable for safety.
The most common adverse events that occurred more frequently in the eltrombopag arms than the placebo arms were upper respiratory tract infection, nasopharyngitis, cough, diarrhea, pyrexia, rhinitis, abdominal pain, oropharyngeal pain, toothache, increased ALT/AST, rash, and rhinorrhea.
Serious adverse events were reported in 8% of patients during the randomized part of both trials, although no serious adverse event occurred in more than 1 patient.
An ALT elevation of at least 3 times the upper limit of normal occurred in 5% of eltrombopag-treated patients. Of those patients, 2% had ALT increases of at least 5 times the upper limit of normal.
There were no deaths or thromboembolic events during either study.
