Results of a Prospective, Open-Label, Phase 4 Study Evaluating the Safety, Efficacy, and Treatment Satisfaction in Adult Immune Thrombocytopenia (ITP) Subjects after Switching to Avatrombopag from Eltrombopag or Romiplostim

Background: A majority of patients with chronic ITP prefer an orally-administered therapy to an injectable therapy, either administered in a physician’s office or at home (Grotzinger KM, et al. Blood 2008) and are more likely to select an oral tablet over a subcutaneous injection and treatment without food restrictions rather than one with food restrictions (McDonald V, et al. Hematology 2021. Jansen AJG, et al. Hematology. 2023. Lucchesi A, et al. Hematology, 2023).

Three thrombopoietin receptor agonists (TPO-RAs) [eltrombopag (ELT), romiplostim (ROMI), and avatrombopag (AVA)] are currently approved in the United States (US) and Europe for the treatment of adult patients with ITP. ROMI is administered via injection, in a health care provider’s office in the US, whereas ELT and AVA are oral medications. Polyvalent cations significantly limit the bioavailability of ELT; therefore, patients must follow strict dietary restrictions. AVA is taken with meals and does not carry food-type or timing restrictions.

A recently published retrospective study of heavily pre-treated ITP patients performed at four large tertiary medical centers in the US demonstrated that a large percentage of AVA patients who switched from either ELT or ROMI achieved a platelet response, regardless of the reason for switch (Al-Samkari H, et al. Br J Haematol 2022).

However, patient satisfaction data following a switch to AVA from another TPO-RA has not been reported in a prospective, controlled manner.

Methods: This was a prospective, multi-center, US, open-label Phase 4 study (NCT04638829) which enrolled patients who had been receiving either ELT or ROMI for ≥90 days and demonstrated a PC response to their prior therapy prior to study entry. Upon enrollment, patients were switched to AVA at a starting dose of 20 mg daily.

Clinic Visits were mandated at Days 15 (D15), 30 (D30), 60 (D60), and 90/End of Study (D90/EOS) with PCs obtained at each timepoint. The Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4, which contains 4 domains (convenience, efficacy, global satisfaction and side effects), was assessed at baseline (BL), D30, and D90/EOS, with a positive change indicating improvement.

The primary endpoint was occurrence of adverse events and serious adverse events.

Secondary endpoints included measuring the change of TSQM from BL and PC post-switch to AVA.

Results: 61 patients were enrolled (38 ELT-switchers and 22 ROMI-switchers).

The mean age at enrollment was 58 years, the median (min,max) time since ITP diagnosis was 3.58 years (0.2,31.0), 37 (61.7%) were female, 43 (71.7%) were Caucasian, and 8 (13.3%) had a previous history of splenectomy.

17/60 (28%) patients self-reported switching due to ineffectiveness, 38/60 (63%) for convenience, and 8/60 (13%) for adverse events with 3 patients reporting 2 separate reasons for switch.

15/60 (25.0%) had a treatment emergent adverse event (TEAE) considered related to AVA. The only TEAE related to AVA in >5% of the population was headache (4/60, 6.7%). 6/60 (10.0%) had a serious TEAE but only 2/60 (3.3%) had a TEAE (headache (1), thrombocytopenia (1)) that led to discontinuation.

Mean TSQM domain scores at BL (convenience, global satisfaction, effectiveness, and side effects) were 71.8, 69.0, 66.7, and 88.5, respectively, reflecting patient satisfaction to ELT or ROMI. Measurable improvement in satisfaction across all domains was observed as the TSQM domain score mean differences (p-value) from BL to D90/EOS were 15.9 (0.0002) for effectiveness, 7.7 (0.0152) for side effects, 13.3 (0.0001) for convenience, and 13.9 (0.0001) for global satisfaction.

The mean percent change from baseline to D90/EOS was 32.9% for effectiveness, 41.5% for side effects, 34.1% for convenience, and 31.3% for global satisfaction following the switch to AVA.

Mean and median PCs were 158x10⁹/L and 138 x10⁹/L, respectively, at baseline for the entire population and were maintained or improved on AVA at 90 days following the switch (152 x10⁹/L and 146 x10⁹/L at Day 90, respectively).

Summary/Conclusion: A population of patients who were generally responding to their prior TPO-RA reported significantly higher satisfaction following a switch to AVA across all domains of the TSQM, Mean/median PCs were also either improved or maintained with AVA treatment suggesting that patients may experience sustained effectiveness paired with enhanced treatment satisfaction when switching from ELT or ROMI.