In a press release full of bravado and hyperbole---"Wrapping up multiple sclerosis at UCSF"-- link Dr. Hauser humble brags about his discovery.
“My hope is that, with these wonderful results against relapsing MS and finally a treatment that works at least partially for PPMS, there will be new octane in academia and industry to make even more meaningful advances,” says Hauser. “MS is no longer a black box. There is so much more that can be accomplished, and we need to build upon this important success.”
Hauser's wording could not be more ironic----as there will most likely be an FDA black box warning for ocrelizumab, due to the risk of deadly infections, malignancies, and patient deaths.
But Montalban noted that there were numerically more malignancies among those in the drug group. There were 11 cancers among those on ocrelizumab compared with only two in the placebo group, something that deserves further monitoring, he said. There was also a numerical imbalance in deaths, with four in the drug group and one in the placebo group.
There were 5 deaths associated with serious infections in the Lupus phase III trial.
The financial press didn't think ocrelizumab would ever get this far. The Wall Street Journal commented on the dangers of the drug back in 2010, when Roche ended its RA drug trial.
Another problem is that autoreactive B cells return after treatment termination, as this study of rituxan in type 1 diabetes illustrated. Autoreactive B cells would create a rebound or relapse after the immune system is reconstituted, similar to what we see with the Tysabri immune reconstitution inflammatory syndrome (IRIS), which occurs after termination of treatment.
We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.
If MS researchers truly want to make breakthrough discoveries, they will have to expand past the EAE mouse model and their narrative of the out of control immune system. They could begin by looking at the the newly discovered lymphatic vessels of the CNS, cerebral endothelial cell permeability, fibrinogen, microbleeds in the MS brain, neurodegeneration and hypoperfusion. If plasmic particles, like viruses, are indeed entering the MS brain through a permeable blood brain barrier, than blocking B cells may not be the best idea. Time will tell.
So much for "wrapping up" MS.....in a billion dollar black box.