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Next-gen B-cell depleting antibody approved for progressive MS

viggster

Senior Member
Messages
464
Ocrelizumab works much like rituximab, depleting B cells. Good long article here goes into how difficult it was for researchers to secure funding to test B cell drugs in MS because the prevailing notions focused on T cells as the culprit in the disease. Now it looks like both types of immune cells are involved. It's the first drug approved for primary progressive MS. Brand name is Ocrevus.

Excerpt:

Armed with journal articles describing their research, Hauser and other researchers applied for a grant from the National Institutes of Health to run a pilot study of rituximab in people.

The NIH said no. The idea was “biologically implausible,” Hauser said they were told. The NIH offered to fund the study if they targeted T cells, he added, but they declined.

“Once we get an idea in medicine, we pivot off that idea very slowly sometimes,” Hauser said.

In 2001, he asked Genentech to fund the study. Initially, he met resistance there as well, he said. A team of outside experts the company assembled to evaluate the proposal rated its chances of success at less than 15 percent.

But some top insiders came to support the idea, and in 2003, after 18 months of discussions, Genentech agreed to a trial.​

https://www.statnews.com/2017/03/28/multiple-sclerosis-ms-drug-ocrelizumab/?s_campaign=stat:rss
 

Murph

:)
Messages
1,799
Seems basically to be the same as Rituximab but human-sourced rather than mouse/human and with longer patent protection?

https://en.wikipedia.org/wiki/Ocrelizumab

I recently also heard about ofatumumab, which is also human sourced and which fluge/mella used for one patient. apparently it's different enough to get a new patent but not enough to have any evidence it does anything different.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Ocrelizumab works much like rituximab, depleting B cells. Good long article here goes into how difficult it was for researchers to secure funding to test B cell drugs in MS because the prevailing notions focused on T cells as the culprit in the disease. Now it looks like both types of immune cells are involved. It's the first drug approved for primary progressive MS. Brand name is Ocrevus.

Excerpt:

Armed with journal articles describing their research, Hauser and other researchers applied for a grant from the National Institutes of Health to run a pilot study of rituximab in people.

The NIH said no. The idea was “biologically implausible,” Hauser said they were told. The NIH offered to fund the study if they targeted T cells, he added, but they declined.

“Once we get an idea in medicine, we pivot off that idea very slowly sometimes,” Hauser said.

In 2001, he asked Genentech to fund the study. Initially, he met resistance there as well, he said. A team of outside experts the company assembled to evaluate the proposal rated its chances of success at less than 15 percent.

But some top insiders came to support the idea, and in 2003, after 18 months of discussions, Genentech agreed to a trial.​

https://www.statnews.com/2017/03/28/multiple-sclerosis-ms-drug-ocrelizumab/?s_campaign=stat:rss

It is good to see this finally coming through. Having shown rituximab worked in rheumatoid, which everyone said was T cells, I tried to get it trialled in MS as he did in around 2001-2. And the resistance to B cells being important is still there. In fact Hauser himself still sees B cells as handmaidens to T cells. One day the penny will drop, but changing ideas in science is a slow business.

We are now on to another generation of antibodies. Ocrelizumab is a bit archaic, but does the job. Ofatumumab is an early generation antibody that has some problems with complement activation and I doubt it will ever be a mainstay of treatment.
 

jaybee00

Senior Member
Messages
592
@Jonathan Edwards

Didn't they trial Ocrelizumab for RA and found high infection rates? Also, there were higher incidences of tumors in PPMS patients....Were tumors an issue for RA patients with Riuximab? Thanks.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards

Didn't they trial Ocrelizumab for RA and found high infection rates? Also, there were higher incidences of tumors in PPMS patients....Were tumors an issue for RA patients with Riuximab? Thanks.

Tumours were not a problem i RA. I think there was something odd about the ocrelizumab trial - it may have been clouded by commercial factors. I would be surprised
if there was a real difference in infection risk.