A large-scale trial of the drug ofatumumab has found it dramatically outperforms existing treatments for relapsing-remitting multiple sclerosis (RRMS). Indeed, in the latter part of the study attacks almost disappeared, raising the possibility the drug may offer long-term elimination of the disease for many.
Multiple sclerosis has several types. Although primary progressive MS (PPMS) is much worse, with no let-up of the symptoms, RRMS is far more common, affecting an estimated 1 million Americans. Existing drugs reduce the frequency of attacks, but they're far from a cure.
Ofatumumab is a monoclonal antibody for the protein CD20, which is expressed on the surface of the immune system's B-cells. It's already approved for use against one white blood cell cancer and under trial for others, while being studied for its potential as a treatment for rheumatoid arthritis.
Like rheumatoid arthritis, multiple sclerosis is an auto-immune disease where the body's natural defenses turn on the organs they are supposed to be protecting, attacking them instead. This has inspired Novartis Pharma and the University of California San Francisco (UCSF) to test the drug against RRMS. In the New England Journal of Medicine, they claim unprecedented success.
More than 900 patients were injected with ofatumumab monthly for an average of 19 months. Across a range of measures, ofatumumab comprehensively outperformed teriflunomide, a widely prescribed MS pill used as a double-blinded control. Those on ofatumumab suffered half as many relapses and ninety percent reported no attacks after the first year of treatment, raising hopes that for many the new drug could mean an end to this condition. Slightly more of the patients were in better health after six months on ofatumumab than were worse - a remarkable achievement for a degenerative disease.
There is no doubt, however, that ofatumumab carries substantial downsides. Weakening a key component of the immune system inevitably makes the body more vulnerable to external attacks. For those on the drug, respiratory tract infections are common, as is anemia. The list of rarer side-effects is long, with many very serious. Those risks will have to be weighed against the crippling effects of RRMS, particularly when it turns into secondary progressive MS where decline continues even between acute attacks.
Hauser has long argued that taming B cells is the key to treating MS. Four years ago, Hauser played a similar role in a study of the B-cell targeting drug ocrelizumab against PPMS. The trial revealed ocrelizumab can slow the disease's progress but not halt, let alone reverse, it. Nevertheless, patients were found to benefit sufficiently relative to placebos that ocrelizumab is now licensed for use and sold as Ocrevus.
Novartis is seeking approval to do the same with ofatumumab but to the many more people with RRMS, and hopefully with even greater benefits.