FDA Accepts NDA for Avatrombopag in Pediatric Thrombocytopenia

Results from the phase 3 AVA-PED-301 trial support the FDA decision for avatrombopag in pediatric thrombocytopenia.

The FDA has accepted a new drug application (NDA) for avatrombopag (Doptelet) as a treatment for pediatric patients 1 year or older with persistent or chronic immune thrombocytopenia who did not experience a response with prior therapy, according to a press release from the drug’s developer, Swedish Orphan Biovitrum AB (Sobi).1

A new drug application was also accepted for avatrombopag for use as an oral suspension. The granules of the oral suspension are sprinkled onto a soft food or in a liquid to prepare for administration.

Results from the phase 3b AVA-PED-301 trial (NCT04516967) presented at the 2024 European Hematology Association (EHA) Congress reveal that the study met its primary end point of durable platelet response, which investigators defined as a platelet count 50 x 109/L or more without rescue therapy in 6 or more of the 8 weeks of the core phase.2 Altogether, durable platelet response between weeks 5 to 12 was observed in 28% (95% CI, 15.8%-39.7%) of patients taking avatrombopag treatment (P = .0077).

Additionally, a main secondary end point of 2 or more consecutive platelet counts greater than or equal to 50 x 109/L without rescue therapy in 6 or more of the 8 weeks of the core phase was met. This was observed in 81.5% (95% CI, 71.1%-91.8%) of patients taking the investigational therapy (P <.0001).

The FDA assigned a Prescription Drug User Fee Act target action date of July 24, 2025, for avatrombopag in treating pediatric patients with persistent or chronic immune thrombocytopenia.

“These application acceptances for avatrombopag brings us one step closer to much-needed, additional treatment options for adolescents and children with persistent and chronic [immune thrombocytopenia],” Jamie Freedman, MD, PhD, chief medical officer at Sobi North America, said in the press release.1 “Now, there is an opportunity to address an unmet need in our pediatric population, with the added bonus of an additional formulation, an oral suspension option that may be more suitable for some patients.”

The double-blinded phase 3b AVA-PED-301 trial enrolled patients between 1 and 17 years old from March 5, 2021, to August 30, 2023, with immune thrombocytopenia of at least 6 months duration and mean platelet counts less than 30 x 109/L. Patients (n = 54) were randomly assigned (3:1) to receive either avatrombopag or placebo for 12 weeks stratified by age, with the study dose adjusted to target platelet counts between 50 and 150 x109/L. Upon competition of the core phase, defined as the 8 final weeks of treatment, or a lack of treatment response to a maximum dose of the study drug, patients could enroll in an open-label extension phase for a maximum of 2 years.

The co-primary end points of the study were platelet count greater than or equal to 50 x 109/L and 2 or more consecutive platelet counts greater than or equal to 50 x 109/L, both without rescue therapy in 6 or more of the 8 weeks of the core phase. Secondary end points included day 8 platelet response, use of rescue therapy, and safety.

Day 8 platelet response of 50 x 109/L or greater were reported in 56% of patients treated with avatrombopag vs 0% with placebo (P <.0001). Furthermore, rescue therapy use in respective arms was 7% and 43%, respectively (P = .0008).

Serious adverse effects occurred in 9% of the investigational arm and 5% of the placebo arm. Additionally, 2 (4%) patients in the avatrombopag arm withdrew due to single instances of leukocytosis and vomiting, and 1 (5%) patient in the placebo arm withdrew due to contusion.

WHO grade 2 bleeding events occurred in 19% and 38%, respectively, with no thromboembolic events or deaths reported in the core phase. In total, 73 patients (97%) entered the open-label extension phase.

References

1. Sobi announces FDA acceptance of new drug application for avatrombopag (DOPTELET®) for the treatment of pediatric immune thrombocytopenia. Press release. Sobi. December 12, 2024. Accessed December 16, 2024. https://tinyurl.com/2p8mtys9
2. Grace RF, Leblebisatan G, Aydinok Y, et al. A phase 3, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of avatrombopag for the treatment of children with chronic immune thrombocytopenia (AVA-PED-301). Presented at: 2024 European Hematology Association Congress; June 14-16, 2024; Madrid, Spain. S318.