The FDA approved a supplemental New Drug Application for avatrombopag as a treatment for adult patients with chronic immune thrombocytopenia who have had an insufficient response to a prior therapy.
The FDA approved a supplemental New Drug Application (sNDA) for avatrombopag (Doptelet) as a treatment for adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a prior therapy.1
“Dova is pleased to provide Doptelet to patients and physicians in the United States for the treatment of chronic ITP in adult patients who have had an insufficient response to a previous treatment,” said David Zaccardelli, PharmD, president and CEO of Dova Pharmaceuticals, the company developing avatrombopag, in a statement. “In addition to offering patients with ITP a new treatment option, we expect Doptelet will also address an important unmet medical need in the market.”
The sNDA for the second-generation, oral thrombopoietin receptor agonist (TPO-RA) was based on the results of the pivotal phase III Amendment 02 trial as well as additional findings from 2 phase II ITP clinical trials. Safety data for the approval were based on 128 total patients with ITP. Additional safety and tolerability findings were supported by the results of more than 1000 patients in studies of avatrombopag across multiple indications.
In the Amendment 02 trial,2investigators studied the safety and efficacy of avatrombopag plus standard of care in comparison with placebo plus standard of care in adult patients with ITP who had received at least 1 prior ITP regimen. Forty-nine of the 100 patients who were screened by investigators met the eligibility criteria for the trial. These patients were randomized to either receive avatrombopag (n = 32) or placebo (n = 17).
For the core study, the duration of exposure was longer in the avatrombopag arm, with 26 of 32 (81.3%) patients receiving avatrombopag over 18 weeks, 17 of 32 (53.1%) over 26 weeks, and 2 of 32 (6.3%) over 30 weeks. Only 3 of 17 (17.6%) patients in the placebo arm were exposed to study medication over 18 weeks, and only 1 patient was exposed for longer than 26 weeks. In the combined core study and extension phase, the mean duration of exposure to avatrombopag was 43.9 weeks, with the longest exposure to the medication being 75.7 weeks.
Data showed that avatrombopag was superior to placebo in the cumulative number of weeks of platelet response with a significantly longer duration of a platelet count ≥50 × 109/L in the absence of rescue therapy versus placebo (median, 12.4 vs 0.0 weeks; mean,12.0 vs 0.1 weeks;P<.0001). Additionally, a greater platelet response rate was observed for patients who received avatrombopag at day 8 versus those who received placebo (21/32; 65.6% and 0/17, 0.0%, respectively;P<.0001).
Results also showed that 5 of the 15 patients who were on concomitant ITP medication in the avatrombopag arm reduced their use of this medication from baseline, while none of the 8 patients who received placebo were able to do so (33.3% vs 0%, respectively; 95% CI, 9.48%-57.19%). However, this was not found to be statistically significant due to the small number of patients who had been using concomitant ITP medications at baseline.
Four patients in the avatrombopag arm experienced grade 3 treatment-emergent adverse events (TEAEs), such as epistaxis, petechiae, headache, and platelet count reduction. Two grade 4 TEAEs were also reported in the core study; one patient experienced a cerebrovascular accident who discontinued study treatment and the other experienced worsening ITP, which was not deemed to be associated with the drug. The most commonly reported TEAEs in the avatrombopag arm were headache, contusion, upper respiratory tract infection, arthralgia, epistaxis, fatigue, gingival bleeding and petechiae.
Avatrombopag was deemed to be well tolerated with a safety profile comparable with placebo when adjusted for treatment exposure. The safety data yielded in the trial proved consistent with phase II studies and 6-month studies that evaluated other thrombopoietin receptor agonists, with headaches being the most frequently reported AE.
Dova announced when the approval was finalized that avatrombopag will be priced similarly to other TPO-RAs used to treat patients with ITP and the company will also offer patient assistance and co-payment programs.