Research

Epratuzumab

Background

Epratuzumab is a humanized antibody which targets CD22, an antigen found on the surface of B-lymphocytes, a type of white blood cell critical to proper immune system function. Elevated expression of CD22 and other B-cell receptor-associated (BCR) proteins on B-lymphocytes has been associated with blood cancers and autoimmune diseases. Epratuzumab’s mechanism of action includes the transfer of BCR-proteins to helper cells called effector cells, thereby reducing B-cell destruction and epratuzumab’s impact on the immune system. We believe epratuzumab is the only antibody in development targeting the reduction of these proteins without severely depleting B cells through a process known as trogocytosis.

We have a research collaboration with Bayer to study epratuzumab as a thorium-227 labeled antibody. We also have some other collaborations ongoing in oncology with independent study groups.

Clinical Studies

Acute Lymphoblastic Leukemia (ALL)

The IntreALL Inter-European study group is conducting a large, randomized, Phase 3 trial combining epratuzumab with chemotherapy in children with relapsed ALL at clinical sites in Australia, Europe, and Israel. This Phase 3 study, which is partially funded by the European Commission, assesses the efficacy and safety of this combination therapy using event-free survival as the surrogate for survival, the primary endpoint.

For adult patients with ALL, there is one ongoing clinical trial. The CheprALL study, sponsored by the French GRAALL study group, is a multicenter Phase 2 trial of epratuzumab combined with chemotherapy also in adult patients with relapsed ALL. Information can be found at clinicaltrials.gov.

References

  • Petri M, Gordon C, Kalunian K, Pike M, Houssiau F, Strand V, Leszczynksi P, Keiserman M, Wegener WA, Wallace DJ, Bongardt S, Kilgallen B, Goldenberg DM. Immunologic Response to Epratuzumab in Patients with Systemic Lupus Erythematosus. 9th European Lupus Meeting, April 23-26, 2014.
  • Strand, V, Petri M, Kalunian K, Gordon C, Wallace DJ, Hobbs K, Kelley L, Kilgallen B, Wegener WA, Goldenberg DM. Epratuzumab for patients with moderate to severe flaring SLE: health-related quality of life outcomes and corticosteroid use in the randomized controlled ALLEVIATE trials and extension study SL0006. Rheumatology (Oxford). 2014 Mar;53(3):512-11.
  • Wallace DJ, Goldenberg DM. Epratuzumab for systemic lupus erythematosus. Lupus. 22(4):400-5, 2013.
  • Wallace DJ, Gordon C, Strand V, Hobbs K, Petri M, Kalunian K, Houssiau F, Tak PP, Isenberg DA, Kelley L, Kilgallen B, Barry AN, Wegener WA, Goldenberg DM. Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up. Rheumatology (Oxford). 52(7):1313-22. July 2013.
  • Rossi EA, Goldenberg DM, Michel R, Rossi DL, Wallace DJ, Chang CH. Trogocytosis of multiple B-cell surface markers by CD22-targeting with epratuzumab. Blood. 2013 Oct 24;122(17):3020-9. doi: 10.1182/blood-2012-12-473744. Epub 2013 Jul 2.
  • Grant BW, Jung SH, Johnson JL, Kostakoglu L, Hsi E, Byrd JC, Jones J, Leonard JP, Martin SE, Cheson BD. A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. Cancer. 2013 Nov 1;119(21):3797-804. doi: 10.1002/cncr.28299. Epub 2013 Aug 6.
  • Advani A, McDonough S, Coutre S, Wood BL, Radich JP, Mims M, O’Donnell M, Elkins S, Becker MW, Othus M, Appelbaum FR. Southwest Oncology Group Study S0910: A phase 2 trial of clofarabine/cytarabine/ epratuzumab for relapsed/ refractory acute lymphocytic leukemia. Blood, ASH Annual Meeting Abstracts. Nov 2012; 120: 2603.
  • Micallef IN, Maurer MJ, Wiseman GA, Nikcevich DA, Kurtin PJ, Cannon MW, Perez DG, Soori GS, Link BK, Habermann TM, Witzig TE. Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma. Blood. 2011 Oct 13;118(15):4053-61. doi: 10.1182/blood-2011-02-336990. Epub 2011 Jun 14.