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Phase I/II Ongoing Study of Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Immune Thrombocytopenia: Extended Follow-up and Long-term Analyses with Optimal Dose

D.J. Kuter1, N. Tzvetkov2, M. Efraim3, Z. Kaplan4, J. Mayer5, P. Choi6, A.J.G. Jansen7, V. McDonald8, R. Baker9, R. Bird10, M. Garg11, J. Gumulec12, M. Kostal13, T. Gernsheimer14, W. Ghanima15, O. Bandman16, P. Arora16, Q. Tran16, H. Guo17, N. Cooper18

1Hematology Division, Massachusetts General Hospital, Harvard Medical School, Boston, United States, 2UMHAT Dr. Georgi Stranski, EAD, Pleven, Clinic of Hematology, Pleven, Bulgaria, 3Multiprofile Hospital for Active Treatment Sveta Marina EAD, Varna, Bulgaria, 4Monash Medical Centre, Clayton, Australia, 5Masaryk University Hospital, Department of Internal Medicine, Hematology and Oncology, Brno, Czech Republic, 6The Canaberra Hospital, Garran, Australia, 7Erasmus MC, University Medical Center, Rotterdam, Netherlands, 8Barts Health NHS Trust, The Royal London Hospital, London, United Kingdom, 9Perth Blood Institute, Murdoch University, Perth, Australia, 10Princess Alexandra Hospital, Woolloongabba, Australia, 11Leicester Royal Infirmary, Leicester, United Kingdom, 12University Hospital Ostrava and Faculty of Medicine University of Ostrava, Department of Hematooncology, Ostrava, Czech Republic, 13University Hospital of Hradec Kralove, Fourth Department of Internal Medicine and Hematology, Faculty of Medicine, Hradec Kralove, Czech Republic, 14University of Washington Medical Center, Seattle, United States, 15Ostfold Hospital Foundation, Gralum, Norway, 16Principia Biopharma Inc, a Sanofi Company, South San Francisco, United States, 17Biostatistics, Sanofi US Services Inc., Bridgewater, United States, 18Hammersmith Hospital, Department of Medicine, London, United Kingdom

Abstract Number: OC 72.2

Meeting: ISTH 2021 Congress

Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Acquired Thrombocytopenias

Background: For most ITP patients, durable remission remains elusive and their disease becomes refractory to current treatments. Rilzabrutinib, an oral, reversible, covalent BTK inhibitor, targets mechanisms of platelet destruction. Preliminary phase I/II results in ITP showed rilzabrutinib was efficacious and safe at all dose levels, including the optimal 400 mg BID dose (NCT03395210).

Aims: Assess efficacy/safety of rilzabrutinib with longer follow-up at 400 mg BID and in long-term extension (LTE).

Methods: Eligible patients had 2 baseline platelet counts <30×109/L. Concomitant ITP therapy was permitted at stable doses. Primary endpoints: safety and ≥2 consecutive platelet counts ≥50×109/L and increased ≥20×109/L from baseline without requiring rescue medication. All patients provided informed consent.

Results: As of 09Nov2020 in 59 patients, 44 initiated rilzabrutinib 400 mg BID and to date, 14 patients with durable, stable response proceeded to LTE at 400 mg BID. For patients initiating rilzabrutinib 400 mg BID, baseline median age was 49 y, median prior therapies: 5.5 (range, 1-53; 25% prior splenectomy), and median platelet count: 16×109/L. 39% of patients initiating rilzabrutinib 400 mg BID achieved the primary endpoint at a median of 20.6 weeks (range, 1.4-24.6) on treatment (Table); 50% had platelet counts ≥30×109/L by day 8. Platelet responses to rilzabrutinib were observed irrespective of prior treatment or responses. LTE patients received rilzabrutinib for a median of 55.9 weeks (range, 13.9-84.3). All LTE patients achieved the primary endpoint response in the main treatment period and maintained platelet counts ≥50×109/L for 96% of the LTE (Figure). Treatment-related emergent adverse events were all grade 1/2, most commonly diarrhea and nausea, with no related bleeding/thrombotic events.

Conclusions: Rilzabrutinib 400 mg BID showed rapid and durable responses and was well-tolerated with longer follow-up and in LTE. This ongoing study continues to assess the magnitude and durability of clinical benefit of rilzabrutinib in ITP.

  Patients, n/n (%)  Primary Endpoint
 (2 Consecutive Platelet Counts
 ≥50×109/L) 
50% of Platelet
 Counts ≥50×109/L
8 of Final 12 Week
 Platelet Counts ≥50×109/L 
  Initiated 400 mg BID 17/44 (39) 14/44 (32) 12/44 (27)

  Completed 
      ≥12 weeks
      24 weeks

17/33 (52)
7/15 (47)
14/33 (42)
7/15 (47)
12/33 (36)
6/15 (40)

  TPO-RA naive 

8/14 (57) 6/14 (43) 5/14 (36)
  Prior therapy  Responded  No Response 

  TPO-RA
  Rituximab
  Fostamatinib 

3/14 (21)
2/7 (29)
2/5 (40)
6/16 (38)
3/14 (21)
1/2 (50)
— —
BID, twice daily; ITP, immune thrombocytopenia; TPO-RA, thrombopoietin receptor agonists.

Table. Platelet Response in ITP Patients Initiating Rilzabrutinib 400 mg BID
Figure. Individual platelet counts over time in LTE responding patients receiving rilzabrutinib (n = 14), including patients with day 8 platelet counts ≥30×10^9/L

To cite this abstract in AMA style:

Kuter DJ, Tzvetkov N, Efraim M, Kaplan Z, Mayer J, Choi P, Jansen AJG, McDonald V, Baker R, Bird R, Garg M, Gumulec J, Kostal M, Gernsheimer T, Ghanima W, Bandman O, Arora P, Tran Q, Guo H, Cooper N. Phase I/II Ongoing Study of Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Immune Thrombocytopenia: Extended Follow-up and Long-term Analyses with Optimal Dose [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/phase-i-ii-ongoing-study-of-rilzabrutinib-an-oral-bruton-tyrosine-kinase-inhibitor-in-immune-thrombocytopenia-extended-follow-up-and-long-term-analyses-with-optimal-dose/. Accessed December 6, 2023.

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