Veltuzumab (Immunomedics), ahumanized, second-generation anti-CD20 mAb whichcontains 90 to 95% human antibody sequences with identical antigen framework regions to epratuzumab (a humanized anti-CD22 mAb) and similar antigen-binding determinants to rituximab (a chimeric, anti-CD20 mAb and the first-line treatment of aggressive and indolent NHL; Rituxan?, Genentech),administered subcutaneously as a single agent, produced anoverall objective response rate of 49% in 47 evaluable patients with relapsed immunethrombocytopenia (ITP), including 15 patients (32%) who reported a complete response.For the 23 patients who responded, median time to relapse from initial veltuzumab dose was 9.2months, with 11 patients (48%) maintaining their response for more than 1 year. These phase I/II study results were presented at the55th annual meeting of ASH?, the American Society of Hematology, held in New Orleans, Louisiana, USA, from December 7 – 10, 2013 by Howard A. Liebman, MD, of the Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.[1]
Veltuzumabshowed activity across all dose levels tested, including the lowest dose of 80 mg x 2, and wasactive in patients with limited disease duration of 1 year or less, as well as in more heavilypretreated patients with chronic refractory disease. Interestingly, 9 patients with the chronic disease had previously receivedthrombopoietin receptor (TPO-R) agonists, such as eltrombopag and romiplostim, which are thenewest approved drugs for patients with chronic ITP who are refractory to other treatments. Outof these 9 patients, 2 had a complete response, one lasted for more than 1 year while the other isstill ongoing at 4.6 months.
?The fact that some patients relapsed to TPOR agonists responded to veltuzumab is particularly encouraging,? commented Cynthia L. Sullivan, President and Chief Executive Officer. ?We are currently evaluating various options for further clinical development of veltuzumab in this and other autoimmune disease indications, as well as in oncology, including licensing arrangements and collaborations with outside study groups,? Sullivan added.
A total of 50 patients with relapsed ITP, 36 of which had the disease for more than 1 year, wereenrolled to receive 2 veltuzumab doses at 80, 160 or 320 mg administered 2 weeks apart or 320mg per dose given once-weekly for 4 weeks. Treatments were well tolerated with no seriousadverse events reported. B-cell depletion occurred after the first dose, even at the 80 mg level. [2][3]
In their presentation, the researchers concluded that low-dose subcutaneous veltuzumab was convenient, well-tolerated, with good B-cell depletion and therapeutic activity across all dose levels and with comparable outcome when administered as 2 doses, 2 weeks apart, or as 4 consecutive weekly doses. Based on the results they believe that further studies in ITP combining subcutaneous veltuzumab with other agents or given as a maintenance regimen is warranted.
For more information:
[1] Liebman H, Bussel JB, Saleh MN, Horne H, Wegener WA, and Goldenberg DM. Comparison Of Two Dosing Schedules For Subcutaneous Injections Of Low-Dose Anti-CD20 Veltuzumab In Relapsed Immune Thrombocytopenia: Final Results Of a Phase I Study [Abstract]
[2] NCT00547066 -Study of Veltuzumab (hA20) at Different Doses in Patients With ITP [Study Record Detail]
[3] Milani C, Castillo J.Veltuzumab, an anti-CD20 mAb for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia and immune thrombocytopenic purport. Curr Opin Mol Ther. 2009 Apr;11(2):200-7.[PubMed]
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