UCB, SA (BRUSSELS, Belgium), licensing partner of Immunomedics, Inc. (Morris Plains, NJ), announced that it has voluntarily, temporarily suspended dosing in the phase III clinical studies of epratuzumab (humanized anti-CD22 antibody) in patients with systemic lupus erythematosus (SLE) because of end-stage manufacturing observations by UCB during a recent routine quality assurance audit of the Immunomedics facilities. These observations, related to the filling processes during final product manufacturing, in UCB's opinion might result in a lack of consistent assurance of sterility in the final dosage form. According to UCB, this is a precautionary measure, taken voluntarily and pro-actively by UCB. No products failing sterility standards have been administered to patients, and no reports of clinical safety issues that suggest an association with these quality assurance observations have been identified. In subsequent discussions with the US Food and Drug Administration (FDA), the authority placed epratuzumab on a "clinical hold." European regulatory authorities have been informed and at least one has also put studies on a clinical hold.

Immunomedics has reported to UCB that it has not encountered any product sterility failures for any batches that have been released for clinical use nor has it encountered any media fill failures. Furthermore, to date there have been no clinical safety reports associated with these observations in the more than 600 patients who have received epratuzumab therapy. UCB and Immunomedics are diligently addressing the process issues and UCB will propose a strategy to the FDA and other authorities to remove the clinical hold status and resume dosing patients by the end of 2006.

UCB has informed Immunomedics they remain fully committed to the further development of epratuzumab in lupus and potentially other autoimmune disease indications. Immunomedics granted UCB the exclusive worldwide rights to develop, market, and sell epratuzumab for all autoimmune disease indications, the most advanced program of which is for the treatment of SLE.

Epratuzumab's target, CD22, is a B-lymphocyte-restricted member of the immunoglobulin superfamily, and a member of the sialoadhesin family of adhesion molecules that regulate B-cell activation and interaction with T-cells. CD22 is rapidly internalized when cross-linked with its natural ligand, producing a potent costimulatory signal in primary B-cells. Epratuzumab binds to domain three of CD22, with high affinity, and once bound, the antibody-antigen complex is rapidly internalized into the cell. Epratuzumab may also block the binding of natural ligands, and may signal, similar to a natural ligand, the down-regulation of the B-cell. This B-cell modulation may also affect T-cell activity, and may explain why complete B-cell depletion is not necessary for epratuzumab's activity, but a combination of mild B-cell depletion with B-cell modulation apparently can result in a therapeutic response. Epratuzumab has been shown to mediate ADCC (antibody-dependent cellular cytotoxicity) in vitro.

—A. Techman