Alexion Pharmaceuticals reports interim results from phase 1 trial on samalizumab antibody

Dec 6 2010

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced the presentation of interim results from the first Phase I/II trial of samalizumab, the company's investigational, first-in-class humanized monoclonal antibody. The ongoing trial is evaluating the safety, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of samalizumab in adult patients with advanced stage B-cell chronic lymphocytic leukemia (B-CLL) or multiple myeloma (MM). Data presented today at the 52^nd American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando indicate that samalizumab was well tolerated at all doses studied, exhibited a dose-dependent biological and pharmacokinetic response, and exhibited initial evidence of anti-tumor activity.

“Samalizumab is designed to target the CD200 molecule, which is overexpressed in certain types of cancer. The early-stage clinical findings presented today are consistent with the predicted mechanism of action of samalizumab and support further study of this novel antibody”

"Samalizumab is designed to target the CD200 molecule, which is overexpressed in certain types of cancer. The early-stage clinical findings presented today are consistent with the predicted mechanism of action of samalizumab and support further study of this novel antibody," said Stephen Squinto, Ph.D., Executive Vice President and Head of Research and Development at Alexion. "We look forward to completing this trial, analyzing the final data set, and further investigating samalizumab as an innovative treatment for patients with other cancers."

Twenty-six patients with advanced CLL or MM were enrolled in the sequential, dose-escalation Phase I/II study. Patients received a single IV dose of samalizumab and were eligible to receive additional cycles of a single IV infusion every 28 days if the first dose was tolerated and patients exhibited at least stable disease. Most patients (77%; 20/26) received multiple samalizumab cycles in dose cohorts ranging from 50 mg/m² to 600 mg/m².

Samalizumab appeared to be well tolerated. Adverse events to date were mostly mild or moderate, and were considered manageable. The most common adverse events included fatigue (50%), headache (20%), fever (20%), and rash (20%). Grade 3 to 5 events deemed possibly, probably, or definitely related to study drug included anemia (8%), neutropenia (8%), thrombocytopenia (4%), reduced visual acuity (4%), respiratory syncytial virus infection (4%), muscular weakness (4%), and rash (4%). Samalizumab dosing was associated with no severe or dose-limiting adverse cytokine reactions. The maximum tolerated dose was not reached in this trial.

In patients with sufficient peripheral immune cells to evaluate biological activity, 95% (19/20) showed 81% to 98% reductions in peripheral CD200+ CD4+ T cells. In addition, 67% (14/21) of patients demonstrated 64% to 75% CD200 loss on B-CLL cells following the first dose of samalizumab, which may represent CD200 down-modulation or CD200+ cell loss. These findings are consistent with the predicted immunomodulatory mechanism of action for samalizumab, which is designed to inhibit CD200-dependent immune suppression, enabling a more efficient immune response against CD200+ tumor cells.

Overall, 36% (8/22) of evaluable patients experienced at least a 10% reduction in bulky disease. Notably, one patient, who received 13 cycles of samalizumab (400mg/m^2), achieved a confirmed partial response as defined in the protocol, with a maximum 71% reduction in bulky disease by CAT scan together with >50% reduction in absolute lymphocyte count while maintaining neutrophil count ≥ 1.5 x 10^9/L.

Source: Alexion Pharmaceuticals, Inc.