Status: formerly approved in European Union

Organizations involved:

CIS Bio International S.A. – Manuf.; R&D; Tech.; Eur. Mark.; Former

Schering AG – Parent; Former

Cross ref: See other radioimmune conjugate entries (ProstaScint, OncoScint CR/OV-In) for information about DTPA antibody-radionuclide linker technology.

Description: Indimacis 125 was a radioimmune conjugate composed of enzymatically derived (cleaved by pepsin) F(ab’)2 fragments of a mouse ascites (in vivo) cultured monoclonal antibody directed to CA 125 ovarian tumor antigen covalently bound to the linker group diethylene triaminepentaacetic acid (DTPA), which is reacted with Indium-111 radionuclide to form the final product, igovomab Fab2-DTPA-Indium-111, used for radiodiagnostic imaging of recurrent ovarian adenocarcinoma. The product was provided as a kit of two single-dose ampules of igovomab (1 mg/mL) and DTPA for reaction to form Indimicis 125 and subquent reaction with Indium-111 in the hospital or regional nuclear pharmacy.

Nomenclature: CA125 Mab Fab2–In111 radioconj. [BIO]; Indimacis 125 [TR]; igovomab [INN]; immunoglobulin G1, anti-(human CA 125 (carbohydrate antigen)) F(ab’)2 fragment (mouse monoclonal OC125F(Ab’)21-chain), disulfide with mouse monoclonal OC125F(AB’)2 light chain, dimer [CAS NAM]; 171656-50-1 [CAS RN]; igovomab monoclonal antibody F(ab’)2 fragment-diethyl-enetriaminepentaacetic acid-Indium-111 [SY]

Biological.: CA 125 is an oncofetal antigen expressed on the surface of over 90% of ovarian adenocarcinomas. Radiodiagnostic imaging with Indimicis 125 was useful to accurately diagnosis tumor regression (relapses).

Companies.: The product was manufactured and marketed by CIS BIO International S.A., then a subsidiary of Schering AG.

Manufacture: Murine hybridomas immunized with human CA 125 were cultured using the ascites methods, i.e., in vivo in the peritoneal cavity of mice. The resulting monoclonal antibodies were subjected to proteolytic cleavage with pepsin, providing active antigen-binding F(ab’)2 immunoglobulin (antibody) fragments, which were purified by chromatographic processes and covalently linked to DTPA. For further information about the ascites method, see the Monoclonal Antibody Products entry (#300) and other relevant radioimmune conjugates in this section.

Status: On Oct. 4, 1996, CIS Bio received centralized European Union approval for Indimicis 125. The company filed to voluntarily withdraw the product on Oct. 2, 1997; and the withdrawal order was issued on Sept. 30, 1999. The product was never approved in the U.S.

Trials: Clinical trials compared Indimicis 125 to ultrasound or computerized tomography. Indimicis 125 scintography provided positive diagnosis in about 50% cases where the other imaging methods were negative. Indimicis 125 was not associated with any significant severe adverse or allergic responses, including no HAMA (antibodies to the murine immunoglobulin component). The 50% efficacy rate is considered low by present standards.