The FDA has approved a supplemental new drug application to expand the use of avatrombopag to include the treatment of adult patients with chronic immune thrombocytopenia who have had an insufficient response to prior therapy.
The FDA has approved a supplemental new drug application (sNDA) to expand the use of avatrombopag (Doptelet) to include the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to prior therapy.1
The approval of the oral thrombopoietin receptor agonist is mostly based on findings from a phase III trial, which demonstrated that avatrombopag led to a platelet count of >50,000 per µL after 8 days of therapy in the majority of patients with chronic ITP, and was also superior to placebo in maintaining platelet counts in the target range during a 6-month period.
The decision to approve avatrombopag was also supported by 2 phase II clinical trials and 2 phase III studies in thrombocytopenia in patients with chronic liver disease (CLD). Moreover, safety data were considered across the 24 studies in the avatrombopag clinical development program, stated Dova Pharmaceuticals, the manufacturer of the agent, in a press release.
“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, MD, president and CEO of Dova. “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. We sincerely thank the patients and dedicated researchers who participated in our clinical program as well as [the] FDA for their collaboration during the review of this application.”
The commercial launch for avatrombopag in this setting is anticipated to occur in mid-July 2019, the company stated.
In the phase III Amendment 02 trial, investigators evaluated the efficacy of avatrombopag plus standard of care (SOC) compared with placebo plus SOC for adult patients with ITP who had received >1 prior ITP treatment, as measured by cumulative number of weeks of platelet response >6 months with once-daily treatment.
The trial, which was conducted from February 6, 2012, to April 9, 2015, included a core study and an extension phase. 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 26/32 (81.3%) of the patients receiving the avatrombopag over 18 weeks, 17/32 (53.1%) over 26 weeks, and 2/32 (6.3%) over 30 weeks. Only 3/17 (17.6%) of 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, the mean duration of exposure to avatrombopag was 43.9 weeks, with the longest exposure to the medication being 75.7 weeks.
Findings 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).
Additional data demonstrated 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.
Regarding safety, patients in the avatrombopag arm experienced grade 3 treatment-emergent adverse events (TEAEs), including epistaxis, petechiae, headache, and platelet count reduction. Two grade 4 TEAEs were also reported in the core study; 1 patient experienced a cerebrovascular accident who discontinued study treatment and the other experienced worsening ITP not deemed to be associated with the mediation. 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 initially approved by the FDA in May 2018 as a treatment for thrombocytopenia in adults with CLD who are scheduled to undergo a medical or dental procedure.
Also in the press release, Dova stated the European Commission also granted a marketing authorization to avatrombopag in June 2019 for the treatment of patients with CLD who have severe thrombocytopenia and are scheduled to undergo an invasive procedure.