Tuesday, 23 May 2017

Be A Hero Ocrevus

Drugs. 2017 May 18. doi: 10.1007/s40265-017-0757-6. [Epub ahead of print]


Ocrelizumab: First Global Approval.

Frampton JE.

Abstract


Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS.



Figure: Key milestones in the development of Ocrevus in multiple sclerosis


We live in hubristic times. By spending time in an elevated position, we come to think of ourselves as gods among men. Wrongfully, or rightfully we misjudge any attack on this inflated self-perception as mere jealousy. And then comes the downfall, because real life isn't rad like jazz or sweet like cinnamon, it is painful in the lessons it teaches the wilful, and the stupid...

Ocrelizumab (Ocrevus) is a humanised anti-CD20 monoclonal antibody that targets B cells, developed by Genentech, Inc. (subsidiary of Roche Pharma) and Biogen Idec Pharma. Genentech, however, is responsible for development of Ocrevus in MS taking on 100% of the costs, while Biogen Idec will receive tiered, double digit royalties on US sales that will approximate its current 30% interest in Ocrevus. Development of Ocrevus in rheumatoid arthritis was halted in May 2010, quoting safety reasons:

"In March, Roche and Biogen Idec announced the suspension of treatment in the ocrelizumab RA program. This decision followed a recommendation from the independent ocrelizumab RA & Lupus Data and Safety Monitoring Board (DSMB). The DSMB concluded that the safety risk outweighed the benefits observed in these specific patient populations at that time based on an infection related safety signal which included serious infections, some of which were fatal, and opportunistic infections. Subsequently, the U.S. Food and Drug Administration (FDA) placed the RA studies on clinical hold".

Results from the pooled analysis of the Phase III programme are open access and available on the internet from Emery et al. 2014 in PlosOne. The authors noted a greater number of serious infections were observed in the high dose group OCR500 + methotrexate (MTX) vs. placebo + MTX. In their own words:

"The conclusion that the two doses of OCR, in combination with MTX tested in the RA clinical trials did not demonstrate a superior benefit-risk profile compared with available treatments led to the termination of the clinical development program of OCR in RA. OCR500+MTX demonstrated clinical benefit by improving signs and symptoms of RA and radiographic outcomes [10][13]; however this dose was associated with an increased incidence of SIEs. OCR200+MTX did not show superior efficacy compared with existing therapies, but was safe and well-tolerated. The clinical development of OCR is continuing in multiple sclerosis, for which there remains an unmet need for more effective therapies and background immunosuppressant therapy is not used".

Eyes wide open...

20 comments:

  1. Not sure about the God thing, but from the MS data I'd say Ocrevus looks pretty good among its high-efficacy peers, and competing with 45% or so secondary autoimmunity, and the n PML on the other high efficacy drug soon approaching four-figure numbers there's some leeway to see what happens once Ocrevus roles out on the large scale. Surely, no complacency, but I get the impression some people at Roche are listening, and perhaps take on board a few hints (http://www.ebiomedicine.com/article/S2352-3964(17)30045-2/pdf), and test them. If wider gaps between infusions control disease just as well, as suggested by some Rituximab (and Ocrelizumab!) data, then the associated reduction of risk may give the drug (and pwMS treated with it) a significantly better (and longer) life.

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  2. I am confused as I keep noting that Ocrevus is only indicated for RRMS and PPMS. Why is it not indicated for SPMS when it is indistinguishable from PPMS on pathology. As well, the borders are very murky between the shift of RRMS to SPMS.

    Is this more Pharma monetary related non-sense by creating MS as 3 imaginary diseases when it is likely just one depending on the individual patient's immune response and reserve? Please give some reasons as to why Ocrevus is not indicated for SPMS patients? Thank-you.

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    1. The trials were not in SPMS so the regulators won't licence for SPMS. But I totally agree it is all bonkers.

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    2. There is this belief that RRMS and PPMS have greater plasticity and therefore less likely to fail as far as trials are concerned

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    3. Ocrevus is licensed in the US for relapsing MS, i.e. (i) early relapsing remitting, and (ii) secondary progressive with relapses, and for primary progressive MS. Little doubt there'll be some creative interpretation of these definition, and I wouldn't be surprised to see a number of pwSPMS *without relapses* on the drug pretty soon.

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    4. It's not that I don't get relapses anymore, just haven't had any remission for years. Sometimes I'm sure things worsen over a few days but I never notice any recovery.

      SPMSers need understanding neuro willing to bend the rules, or wait for siponimod or go off-label...

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    5. Why is siponimod only indicated for SPMS and not PPMS for that matter? Can a blinded neurologist tell clinically, on MRI, on LP with CSF analysis, or even on pathology samples, the difference between SPMS and PPMS?

      These imaginary classification systems (RRMS, SPMS and PPMS) of MS are going to end up excluding many MS patients from possible efficacious treatments.

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    6. Sad thing is even when some neurologist are not blinded they still can't tell, otherwise there weould not be so many mis diagnoses:-)

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  3. I just got a call about my last JCV titre level, glad to hear this today.

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  4. I trust Ocrelizumab will not hold up research and development of better, safer and more effective therapies for progressive MS. Ocrelizumab seems to me like another blunt instrument, wrecking ball.

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    1. We're only now touching on B cell therapies after exhausting the T cell side of things. The pathologists haven't really added anything new with regard to PPMS or SPMS as far as the damage which leads to disease progression. I've always felt that the answer to progressive disease once it has occurred is neuroprotection and boosting neuroplasticity (sodium channel blockers as an e.g.). Early on of course, it's all about disease modifying treatments.

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    2. Yes, this sounds like a route to much more effective, intelligent therapies for progressive MS.

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    3. At the moment with pharma, it's a case of if all you have is a hammer every problem looks like a nail but as NDG says we need neuroprotectants too to really make a diference. Progress on this at least clinically (not us experimentalists) remains painfully slow.

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    4. Sodium channel blockers don't boost neuroplasticity though. They may well protect cells from death if sodium channels are disfunctional but overall I'd say they reduce neuroplasticity.

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  5. Anon 6.04 wrote
    Dear Prof G and co. If you bravely look at the fb page of ccsvi inms, they are practically gloating the failure of ocrevus. They also claimed m to know the cause of ms and that you are only in it for the money (**** ****). It comes up on my fb feed and their smugness and lack of compassion for those who have to be liberated more than once stinks to high heaven,

    Thanks.....Gloating at Failure is a poor trait and yet it is a success as ocrevus is licensed and available in the USA. In relation to failed approached one could look in the mirror but this is not a success because people are being conned into liberating their cash.

    However, it is good to see that you have identified one of our resident trolls, from Leicester who regularly visits our spam folder. They normally say "we are covering our backs" and much worse.

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  6. I am glad that the troll goes straight to spam. I can't imagine that the troll is 'cured' but feels strong. Tthe same remarks were made about LDN,, by the same troll. Life is weird. People are living and doing well on various drugs and therapies and are glad that something slows this disease. The other type of energetic commentator swears that they'd never touch apharma drug, as though it was a criminal activity to accept a Dmd.
    These trolls need to learn that reality is tough. That ms dies down and then can attack without warning. It resembles the arguments about vegetarianism and vegans and religion and atheism. MSI is not a religion. Why do people bring it down to w system of belief? It's a disease of the brain and vervous system. Aha! Belief that one can cure
    MS is a type of infirmity itself.

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    1. Troll still posting (new one today, same old same old) and still going straight to spam, now what did Einstein say about doing the same thing and expecting a different result.......? ;-)

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  7. I'm going to write something I've wanted to express for years. GET LOST TROLL! YOU ARE WRONG!

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  8. I am late to the conversation who is The Troll?

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    Replies
    1. put it this way walkers crisps aren't the only thing to come out of Leicester

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