Disappointing results from trial of another MS "mab" drug

The biotech company Centocor (Malvern, PA) and an international team of clinical investigators have just released results from a phase 2 dose-finding trial of its monoclonal antibody drug ustekinumab. Ustekinumab binds to the p40 antigen which is a component of two inflammatory proteins, IL12 and IL23, which have been both detected in MS lesions. It neutralizes these proteins, preventing them from stimulating the production of other inflammatory proteins such as IFN-gamma and IL17. Ustekinumab had been found effective against EAE in pre-clinical trials, and was also found to be safe in phase 1 trials, so the investigators were hopeful that it would help reduce MRI lesion formation and relapses in people with MS.

Unfortunately, none of the doses studied resulted in a significant reduction in lesions or relapses compared with placebo. On the bright side, no permanent serious side effects occurred, and the drug didn't seem to exacerbate MS disease activity (as in the case of TNF-alpha). The authors offered suggestions as to why the drug worked in EAE but not in MS. For instance, while the drug was administered in the early stages of EAE, the MS subjects had a disease duration of two years on average. Alternatively, the pathways targeted by this drug may not be a crucial component of MS disease activity. Either way, it's back to the drawing board.