Immunomedics, Inc. IMMU, a
biopharmaceutical company primarily focused on the development of monoclonal
antibody-based products for the targeted treatment of cancer, autoimmune and
other serious diseases, today announced that subcutaneous administration of
veltuzumab, as a single agent, demonstrated promising activity in patients
with relapsed immune thrombocytopenia (ITP), even in more heavily treated
patients with the chronic disease, and in patients with chronic lymphocytic
leukemia (CLL).
Veltuzumab is a second generation humanized anti-CD20 antibody constructed
using the same human donor frameworks as epratuzumab, the Company's humanized
anti-CD22 antibody. The complementarity-determining regions (CDRs) of
veltuzumab are identical to rituximab, except for one amino acid residue,
which appears to give veltuzumab some unique properties. In an animal model of
human lymphoma, veltuzumab demonstrated higher efficacy than rituximab, and in
cell culture experiments, this humanized antibody showed slower off-rates and
increased complement-dependent cytotoxicity compared to rituximab.
In a published study, veltuzumab reversed life threatening anemia and
thrombocytopenia in a patient with systemic lupus erythematosus who was
unresponsive to rituximab. In non-Hodgkin lymphoma (NHL) patients who had
received prior therapies, 4 once-weekly infusions of veltuzumab produced a
complete response rate of 25% in a study of 84 patients, even at the low dose
of 80 mg/m^2 given intravenously.
A subcutaneous formulation with a high concentration of veltuzumab was
developed to avoid the need for lengthy intravenous administration and
dedicated infusion suites. Published results show this formulation, which can
be administered within a few seconds due to the low injection volume, to be
active in patients with NHL. (For more information, please refer to the
Company's 2011 publication by Negrea et al. in Haematologica, volume 96, pages
567-73).
In the presentation given at this ASH meeting, two subcutaneous dosing cohorts
were evaluated in a Phase I/II study in relapsed ITP. The first cohort of 34
patients received 2 veltuzumab doses at 80, 160 or 320 mg administered 2 weeks
apart for a total dose of 160, 320 or 640 mg, respectively. The second cohort
is enrolling patients to receive veltuzumab at 320 mg per dose given
once-weekly for 4 weeks for a total dose of 1280 mg. Thus, four different
doses are being evaluated.
At the time of reporting, 10 patients were enrolled into the second cohort,
with 1 patient rolled over from the first cohort. Among the 44 patients
enrolled, 42 were evaluable for efficacy. The overall objective response (OR)
rate was 50%, with 12 patients (29%) having a complete response (CR), which
means that their platelet levels rose to or above 100,000 per µL.
For the 12 patients with ITP one year or less, OR and CR rates were 58% and
25%, respectively. For the 30 patients who had the more refractory, chronic
disease, of which 50% had the disease between 5 to 37 years, 47% still
achieved ORs, including 30% CRs. Responses occurred across all doses tested,
including the lowest dose at 80 mg x 2.
Response durability from initial dose was available from patients in the first
cohort only. Of the 17 patients who responded to subcutaneous veltuzumab, the
median relapsed-free survival was 8 months, with 47% of responders maintaining
their response longer than 1 year. Seven responding patients had been
retreated, with 2 patients (29%) achieving responses comparable to their
initial responses.
This multicenter study was presented by Howard A. Liebman, MD, of the Jane
Anne Nohl Division of Hematology, Keck School of Medicine, University of
Southern California, Los Angeles, CA, and included also Georgia Cancer
Specialists, Marietta, GA; Weill Cornell Medical Center, New York Presbyterian
Hospital, New York, NJ; and Low Country Cancer Care Associates, Savannah, GA.
In oncology, the Company has previously reported that 4 subcutaneous
injections of low-dose veltuzumab given 2 weeks apart produced responses in 17
NHL patients that are comparable to intravenous doses.
For CLL, however, high levels of circulating leukemic cells may require more
frequent and prolonged dosing. Thus, a multicenter, open-label, Phase I study
of single-agent veltuzumab therapy was undertaken to evaluate 2 different
subcutaneous dosing schedules. Over an 8-week treatment period, three dose
levels of veltuzumab at 80, 160, or 320 mg were either injected once every 2
weeks for a total of 4 doses (cohort 1), or given twice weekly for a total of
16 doses (cohort 2). A total of 11 patients with newly diagnosed or relapsed
CLL had been enrolled into the first cohort, with cohort 2 currently having 10
patients enrolled.
Results from 18 assessable patients were presented by Matt E. Kalaycio, MD, of
Cleveland Clinic's Taussig Cancer Institute, Cleveland, OH. Other research
sites included Low Country Cancer Care Associates in Savannah, GA; Weill
Cornell Medical College in New York, NY; and the Carol G. Simon Cancer Center,
Morristown, NJ. The overall disease control rate was 83%, with 12 patients
having stable disease (SD) and 3 patients (17%) reporting a partial response
as their best responses. Four SD patients had relapse-free survival for 6 – 12
months and all 3 partial responders were relapse-free at 6, 12 and 24 months.
Despite cumulative doses ranging from 320 to 5120 mg, similar disease control
rates were observed across all 3 dose levels (80 vs. 160 vs. 320 mg) and
dosing schedules (cohort 1 vs. 2).
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