The increases in gastric biomarkers in people chronically given approved doses of avatrombopag were insignificant, according to a new study published in the British Journal of Haematology. This is contrary to the gastric toxicity seen in rat models in preclinical trials.
“These results confirm clinical data that there appears to be a low risk of gastric toxicity with long-term avatrombopag dosing,” the authors of the study concluded.
Read more about ITP treatment
The safety of avatrombopag has already been shown in clinical studies, and the treatment is already approved to treat immune thrombocytopenia (ITP) in adult patients as well as in patients with liver disease requiring a procedure.
However, preclinical studies in rats showed that treatment with avatrombopag led to degeneration, regenerative hyperplasia, and atrophy in gastric fundic glands.
Here, a team of researchers from the United States screened 64 patients who received long-term avatrombopag as part of 2 clinical trials for atrophic gastritis.
They found no significant changes in the mean levels of gastric biomarkers from baseline over the course of the trials, and all mean and median gastric biomarker levels were within the normal range at all time points.
The researchers also reported that there seemed to be no association between a higher dose or a longer duration of avatrombopag treatment and higher levels of gastric biomarkers.
“These data demonstrated that, unlike preclinical studies in rats in whom gastric toxicity was observed with extremely high avatrombopag doses, chronic avatrombopag dosing in humans at approved doses was associated with insignificant increases in gastric biomarkers,” the researchers concluded. “No data demonstrating gastric toxicity were observed.”
ITP is a rare bleeding disorder characterized by unusually low platelet count, leading to petechiae, purpura, ecchymoses, nosebleed, mucosal bleeding, and hematuria.
Avatrombopag is an oral, small-molecule thrombopoietin receptor agonist that increases platelet count.
Reference
Bussel JB, Tarantino MD, Lee EJ, Jamieson BD. Plasma gastric biomarker evaluation with avatrombopag dosing in patients with chronic immune thrombocytopenia in phase 3 trials. Br J Haematol. Published online June 6, 2023. doi:10.1111/bjh.18897
