Two weeks ago the annual meeting of the ECTRIMS was held in Amsterdam. As usual, several interesting presentations, some of them probably good enough to change the immediate future of MS clinical practice, were presented. Among them, new data regarding the next 3 new oral therapies that probably will be approved when their results are published, laquinimod, teriflunomide and BG-12. These therapies will need a specific review later on. But the focus of this post is on the data of the phase II trial testing Ocrelizumab in MS.
Ocrelizumab is a humanized monoclonal antibody targetting the CD20 B-cell marker. It depletes B lymphocytes. It is the molecular and commercial son of Rituximab and the diseases to which is aimed are the same as Rituximab. In fact, what we all expected was that Ocrelizumab improved safety and reduced infussion reactions due to its humanized nature (while Rituximab is chimeric). Rituximab had been tested before in MS with notable success. However, as we explained before, that study did not lead to a phase III trial due to commercial interests. Then its humanized version was tested expecting more safety and tolerability. But it happened that, paradoxically, Ocrelizumab turned out to be less safe. At least, while in Rheumatoid Arthirtis and Lupus Rituximab severe adverse events were very infrequent, their trials with Ocrelizumab were prematurely halted because of several fatal opportunistic infections.
In MS the Ocrelizumab phase II trial was continued and, again, a death in the Ocrelizumab arm raised concerns regarding its safety. Now we have additional data regarding both safety and effectiveness. The 96 week results of the phase II trial of Ocrelizumab in MS were presented in ECTRIMS and simultaneously published in Lancet. Effectiveness data are extraordinary. Reduction of 89-96% of the rate of new gadolinium-enhancing lessions and around 80% for relapses… As expected, those results were similar to the ones obtained with Rituximab. In every other context those data will be enough to develop a phase III trial and probably get approval when completed. If we did not have Rituximab i would be pussing for Ocrelizumab phase III trial, but i can’t knowing what we know: A woman died (out of 200 patients). In the supplementary material of the The Lancet paper there is a detailed description of what happened. Infection was not detected and this patient had been stung by a wasp days before. But this patient has to be added to those of the RA and lupus trials and not be neglected.
We have then, a very good therapy, pretty safe and with a huge use experience, Rituximab. We have a very good therapy, not so safe or, at least, that raises serious concerns about some safety issues, some of them leading to patients’ deaths and that has not been used in clinical practice yet. What should we do? I think that if we, neurologists, have any trace of common sense, we should push for a phase III trial on Rituximab, convince Roche and Biogen of getting rid of Ocrelizumab (their losses can be still higher if they keep pushing that option) and persuade them that they have a nice therapy, that probably no other company will challenge on the short term and will give them profits for sure. In my opinion that is the best way of saving governments and companies money, accelerating the approval of a new therapy for aggressive MS and avoiding unknown risks. The alternative should be a public or privately funded (through foundations or patients’ associations) alternative trial to overcome the commercial criteria in drug development.
What do you think?