Ocrelizumab

[Lars]

I was going through the clinical trials list and saw that Ocrelizumab is, or is still recruiting for phase 2. I'm wondering if this is really just Rituxan with a more complicated name or is this a way to get around the financial loss of a soon to expire patent on Rituxan? They must have tweaked it more than just the name.
Lars

[patientx]

I don't have the info at hand, but I think Ocrelizumab targets a different protein on B-cells. I think I also read somewhere that it may not have some of the toxic side effects of Rituxan.

[dignan]

I think this explains it...

Ocrelizumab is a humanized monoclonal anti-CD20 antibody constructed with recombinant DNA techniques and designed to selectively target CD20 B cells. (Rituxan is a "chimeric murine-human monoclonal antibody".) In vitro characterization of ocrelizumab demonstrated enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and reduced complement-dependent cytotoxicity (CDC) as compared with rituximab. Ocrelizumab binds to a different, but overlapping, epitope of the extracellular domain of CD20 as compared with rituximab.

http://www.reumagalicia.com/addonsdata/ ... iculo9.pdf

[Manu]

And now it is in Phase III trial


Regards
Manu

[Pesho]

Today I was 12 hours in the hospital for tests and Ocrelizumab infusion and Rebif shot, one of them is a placebo. Didn't feel any side effects from Rebif, but it is a small dose, so there might not be any. Two hours after the Rebif shot, and hour and a half on Ocrelizumab infusion I felt a lot warmer, but my temperature was normal. So I really don't know what I''m taking yet, hope over time things will be more clearer. Manu, how are you feeling, you are on the test program for some time now?

[Pesho]

Got my second infusion today. Was feeling a bit hot at moments, also my blood pressure went from 110/70 to 120/80 at the end of the infusion, but still normal for a man my size. After that went for a four hour walk shopping stuff. Felt my legs a bit stiff after 3+ hours on bed, but things got better with walking . So, no side effects to Rebif, no side effects to Ocrelizumab. Still on a low dose of Rebif, will see how it goes in 2 weeks when I get to Rebif 44, for now I only have red spots on the injection sites, and not from all shots.

[Manu]

Got my second infusion today. Was feeling a bit hot at moments, also my blood pressure went from 110/70 to 120/80 at the end of the infusion, but still normal for a man my size. After that went for a four hour walk shopping stuff. Felt my legs a bit stiff after 3+ hours on bed, but things got better with walking . So, no side effects to Rebif, no side effects to Ocrelizumab. Still on a low dose of Rebif, will see how it goes in 2 weeks when I get to Rebif 44, for now I only have red spots on the injection sites, and not from all shots.

Any news so far ?


manu

[Pesho]

Sorry, didn't check the thread till now. Nothing new. Rebif injections have no effect on me, I mean side effects. Had some headache and sweating in the beginning, but it might have been psychological. I feel just like when I got out of the hospital. Walking is normal, I can run and so on. Just I have pain in the knees and below them to the ankle. Doctors say this is not from MS and I have to go to other doctor at some point, like joint doctor . Next infusion is in the middle of October. Thinking about HSCT, because I'm not bad, but I don't feel good.

[Gogo]

" The Lancet, Volume 379, Issue 9822, Pages 1196 - 1197, 31 March 2012 <Previous Article|Next Article>doi:10.1016/S0140-6736(12)60508-XCite or Link Using DOIOcrelizumab in multiple sclerosis: risks and benefits
Original Text
Abhijit Chaudhuri aI have several concerns about the clinical trial by Ludwig Kappos and colleagues (Nov 19, p 1779)1 of the monoclonal antibody ocrelizumab in relapsing-remitting multiple sclerosis.
First, I disagree that ocrelizumab has a benign safety profile. The death of a patient in the high-dose group was the direct effect of a drug that has been widely associated with a serious risk of infection in other studies.2 The natural history of multiple sclerosis3 suggests that the ultimate cause of death in these patients is infection; immunosuppression could potentially accelerate the process.
Second, the outcome data did not show a dose-response relation. This finding, and the time course of treatment response, make it highly unlikely that escalation of B-cell depletion by immunotherapy alters the natural course of multiple sclerosis.
Third, the putative benefit from immunotherapies in multiple sclerosis is largely driven by MRI markers that do not correlate reliably with long-term disability. Kappos and colleagues did not provide scores on the expanded disability status scale at weeks 24 and 48, so it is not possible to make a comparison with baseline scores. Of interest is that there was no difference in serious relapse of multiple sclerosis between the treatment groups.
One must use extreme caution in accepting the published trial data as proof of the concept of B-cell-driven pathogenesis in multiple sclerosis. Indeed, most authors of this paper were also involved with the clinical trial of B-cell-targeted treatment with atacicept that was terminated by the sponsor because of serious worsening of disease in the treated groups (ClinicalTrials.govNCT00642902).
The lessons from the clinical trial of natalizumab4 seem to have been forgotten too quickly: nearly a quarter of more than 200 patients with natalizumab-induced progressive multifocal leukoencephalopathy are dead and most of the rest are severely disabled by the drug rather then their disease. Quo vadis multiple sclerosis?
I declare that I have no conflicts of interest. "

http://www.thelancet.com/journals/lance ... S0140-6736(12%2960508-X/fulltext

[Pesho]

Got my second infusion yesterday. No side effects, during the infusion. Just found out that a second patient has died in the trial, no reason for death connected with Ocrelizumab found for now. Had a mild headache in the evening, maybe the two beers that I had in the evening have something to do with that . Some headache in the day after, but overall I'm feeling normal. No side effects from Rebif either, so the doctors are also puzzled what I'm having.

[Pesho]

Got some bad case of sour throat... Almost a month now, going trough a second course of antibiotics and a whole bunch of other medicine. And it is not going away . I always had a bad throat, but this is getting way too bad. If I'm on ocrelizumab my immune system is suppressed and I'm out of luck. And the winter is not even here...