Photo courtesy of the FDA
The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) to treat children age 6 and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Eltrombopag is an oral thrombopoietin receptor agonist that works by inducing the stimulation and differentiation of megakaryocytes to increase platelet production.
The drug is already FDA-approved to treat adults with ITP.
The FDA’s latest approval of eltrombopag was based on data from the phase 2 PETIT trial and the phase 3 PETIT2 trial.
“Young patients with chronic ITP who have either an insufficient response to or side effects from standard therapies have limited treatment options, making this FDA approval of eltrombopag for children 6 years and older particularly important,” said James B. Bussel, MD, a professor at Weill Cornell Medical College in New York and lead investigator of the PETIT study.
“Through the eltrombopag studies, one of which is the largest randomized trial ever performed in children with chronic ITP, we discovered that Promacta—a treatment that can be taken once daily by mouth and shown to be well tolerated—can manage this disorder and help these young patients.”
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. Eltrombopag dose was titrated to a target platelet count of 50-200 x109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x109/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 x109/L.
The primary efficacy endpoint was the proportion of subjects who achieve platelet counts of 50 x109/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 occurring 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 or 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 (1%).
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.
Eltrombopag is marketed as Promacta in the US and Revolade in most countries outside the US. For more information on the drug, see the full prescribing information.
