Genentech asks ImmunoGen to devise scale-up
firm Immunogen to develop a commercial manufacturing process for
its anticancer drug trastuzumab (Herceptin) using its
tumour-activated prodrug (TAP) technology.
The challenge for Immunogen will be to scale the production of trastuzumab-DM1 up to a commercial level, as the company has until now only manufactured TAP compounds as far as preclinical and initial clinical testing.
DM1 is a potent cell-killing agent ImmunoGen specifically developed for antibody-guided delivery to cancer cells, so during the manufacturing process the cell-killing agent has to be attached to the antibody in a manner that does not significantly impact the binding properties of the antibody.
In the past few years, ImmunoGen has manufactured, in a smaller scale, ten TAP compounds at its good manufacturing practice (GMP) production facility in Norwood, Massachusetts.
Examples of them include huC242-DM4, currently in Phase I testing for the treatment of colorectal, pancreatic, and other cancers that express the CanAg antigen, and AVE9633, in development by sanofi-aventis, which advanced into clinical testing in March 2005.
Trastuzumab-DM1 now has an effective Investigational New Drug (IND) application, and Genentech aims to use the manufacturing process developed by Immunogen to make the drug once it has been approved for commercialisation.
"This is a new thing for us, developing a large-scale commercial manufacturing process for another company," Immunogen spokeswoman Carol Hausner told In-PharmaTechnologist.com.
"There are obviously several processing steps to consider, such as separation and purification, but the two actual reactions are putting the linker on and adding the cell-killing agent."
Nevertheless, manufacturing antibody-targeted chemotherapeutic agents on a commercial scale is not a novel task; Wyeth's gemtuzumab ozogamicin (Mylotarg), already in the market for the treatment of patients with CD33-positive acute myeloid leukemia (AML), is also based on a 'linker' technology that combines a potent anti-tumor antibiotic with an antibody that binds to a protein on a cancer cell.
ImmunoGen will receive research support payments for its work and will be supplied with the antibody by Genentech.
The two companies also agreed to amend a 2000 agreement that grants Genentech exclusive rights to use ImmunoGen's TAP technology with therapeutic antibodies to HER2, a protein over-expressed in approximately 20 to 30 per cent of breast cancer patients.
This amendment increases the total potential milestone payments to ImmunoGen under this agreement by $6.5m (€5m) to $44m and also boosts the potential royalties to ImmunoGen on any HER2-targeting TAP compound developed by Genentech, including trastuzumab-DM1.
All in all, seven companies have licensed access to Immunogen's TAP technology: Genentech with four licences, Centocor, Biogen, sanofi-aventis, Boehringer Ingelheim, Millennium Pharmaceuticals and Amgen.
