Thursday, 18 February 2016

Ocrelizumab gets thumbs up from the FDA for fast track for Primary Progressive MS

#MSresearch #Primary Progressive MS Good news

GoodNews  for PPMSers for a change. The FDA has agreed to fasttrack the accessment of ocelizumab and its trade name is born


Breakthrough Therapy designation is a United States Food and Drug Administration expedited drug development tool, which allows the FDA under Section 902 of the July 9, 2012 Food and Drug Administration Safety and Innovation Act, to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases.
A breakthrough therapy designation can be assigned to a drug if "it as a drug which is intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition" and if the preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development

U.S. FDA grants Breakthrough Therapy Designation for Roche’s investigational medicine ocrelizumab in primary progressive multiple sclerosis

Ocrelizumab is the first investigational medicine to receive Breakthrough Therapy Designation in multiple sclerosis (MS)

Roche announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for the investigational medicine ocrelizumab (OCREVUSTM) for the treatment of people with primary progressive multiple sclerosis (PPMS). There are currently no approved treatments for PPMS, a debilitating form of MS characterised by steadily worsening symptoms and typically without distinct relapses or periods of remission.

Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The designation is based on positive results from the pivotal Phase III study (called ORATORIO), which showed treatment with ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo. Top-line results were presented at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October 2015.

Roche plans to pursue marketing authorisation for both PPMS and relapsing multiple sclerosis (RMS), a more common form of the disease, and will submit data from three pivotal Phase III studies to global regulatory authorities in the first half of 2016.

OCREVUS is the proprietary name submitted to global regulatory authorities for the investigational medicine ocrelizumab.

p.s. This corrects my mistake calling it OCREVUSTM which was a slip up after a cut and paste removed the superscript from trade mark (TM).....LoL

This is great news however it is not a done deal and we will have to wait and see whether there is a green light for all of primary progressive MS or whether they will be pinned back to "active" primary progressive MS and whether there are any other issues that the regulators come up with once they get to see the full data package.

Who makes up these names?.....OCREVUSTM...Indeed

34 comments:

  1. Thanks for posting this, MD. Do we have any idea when us plebs will get a look at the full data package? Will it be made public when it's presented to the FDA?

    I'm curious about the numbers for the secondary malignancies that they mentioned (how many of each type), and as to how the malignancy rates compare to those of Lemtrada and Cladribine.

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    1. You will never see the full package unless you do a freedom of information request and this could definately be got from the EMA, but the main data will be published in papers, perhaps this year.

      I believe the malignacies would set alarm bells going if the PPMS trial was examined in isolation as it was quite abit higher than the placbo arm and that occurring in the doomed cladribine studies but it will be dressed up with the data from the RR trials and suspect the malignancy rate is very similar to other DMT.

      Mark (http://www.wheelchairkamikaze.com/2015/10/ocrelizumab-update-rrms-trials.html) points out 11 ocrelizumab verses 2 in plaecbo, which is consistent with what I heard on the grapevine at ECTRIMS remember cladribine was rejected on 0 placebo verses 3 (originally 6 stated, but 3 would fall by the wayside)

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    2. Might this, then, be good news for the folks trying for a second time to get Cladribine licensed for MS? If Clad has one third, to one quarter of the malignancy rates of Ocrelizumab, and roughly the same effectiveness (not counting the PPMS CPD decrease), it seems like it would be given the green light if Ocrelizumab gets the ok.

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    3. I dont think that Merck is going to FDA for approval, and I bet the malignanct rates are similar. The FDA/EMA were rather blinkered because another trial is not the way to see if there is a cancer signal, it is better to use and monitor as a 2 year trial is reallly too short to expose a cancer risk.

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    4. Thanks very much for the mention of my blog, Wheelchair Kamikaze. As you have reiterated here in the comments section, I see no reason to believe that Ocrelizumab will be any more effective than Rituxan in treating PPMS patients who don't display active inflammatory activity. Seems like the drug company is going to great lengths to stack the deck, first over populating their trial with patients who had the greatest chance at responding, and then withholding full trial results until, it seems, the last possible moment.

      While it is of course encouraging to see any progress being made towards treating PPMS, in some ways getting an Ocrelizumab FDA approval for treating PPMS might actually be a setback for patients with the disease. We know with a reasonably high degree of certainty that Rituxan did not stop progression in the vast majority of PPMS patients it was trialed on. Since the two drugs share a mechanism of action, Ocrelizumab can't be expected to be somehow more effective than its older cousin. An FDA approval, though, would put the focus back on modulating and/or suppressing the immune systems of progressive MS patients, when in fact an entirely new approach is most likely needed.

      Immunosuppression within the CNS may prove to be effective in SPMS patients who develop tertiary lymphatic tissues within their central nervous systems, and I'm surprised this approach hasn't been looked at more vigorously. However, PPMS patients generally don't display such lymphatic tissues, further making the likelihood of immunosuppression being successful less likely.

      Am I way off base here, or is my skepticism towards Ocrelizumab and PPMS justified? After all, the drug was developed simply because Rituxan was soon due to come off patent. Hard not to be cynical under these circumstances.

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  2. Am sure that I am not alone; I wonder what price this is going to be? Still good news.

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    1. At least as expensive as natalizumab, maybe more I predict

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    2. When in the infusion room sometimes I see people starting their rituxin and they get a couple of benedryl. I assume this dampens something. Would that still be the case with Ocrevus since it is more humanized does it produce less of a reaction?

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    3. Rituximab is chimeric and so injection reactions/allergies could be a problem (30%) ocrevus should reduce this (<5%) and this should be reduced further with ofatamumumab

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  3. How to pronounce OCREVUSTM?

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    1. Its pronounced EXPENSIVE lets hope its EFFECTIVE.

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    2. Och Re Vust Um
      Is my take

      If you don't use English you are going to get all sorts of pronounciation
      Let's hope it doesn't spell PML


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    3. Since it is pretty much the same as Rituximab I would expect the PML risk to be a fraction of Tysabri.

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    4. You one of our Swiss visitors today? ;-)

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    5. It would be nice if you guys could post how to pronounce various MS drug names. For eg - I would like to know if there is an emphasis on 'o' in Copaxone, what does the 'g' sound like in gilenya. I have heard doctors and nurses pronounce them many different ways!

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    6. Co Pax Own (Copaxone) Ow Badge Ee Oh (Aubagio) Am Pie Ra/Fam Pie Ra
      Av On Ex (Avonex). Tie Sab Ree (Tysabri), Ree Biff (Rebif), Jill En Ya (Ja) (Gilenya), Beta Seer On Beta fear On (betaseron/betaferon), Lem Trar Da (Lem trada), Pleg Rid ee (Plegridee)

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    7. I think that the tm on the end lost its superscript from the press release. It looks like it should just be Ocrevus

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  4. Is this Friday session something to do with the long-awaited subgroup analysis?

    #ACTRIMS2016 http://www.actrims.org/forum2016/index.php/program/full-program
    Friday, February 19
    4:20 pm- 4:30 pm Talk 3: Efficacy of ocrelizumab in patients with PPMS with and without T1 gadolinium-enhancing lesions at baseline in a Phase III, placebo-controlled trial
    Jerry Wolinsky (The University of Texas Health Science Center of Houston)

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    1. This may show that it is not activity dependent because you GAD enhance for 2 week. So you are negative but you get a lesion one month later and enhance. Surely they should link it to T2 lesions but hey this may be how you get a licence. Pharma don't care if people take a drug that doesn't work for them look at the 70% on beta interferons :-(

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  5. Hmm... But isn't Ocrelizumab still a wrecking ball / blunderbuss? Roll on Charcot project!

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  6. It's Ocrevus, if you look at the source article you'll see the TM for trademark.

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    1. LOL. I copied it from Roche website or is it the Ro website as it is based in switzerland.so they don't do superscript

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    2. Corrected. It has made my day maybe we should call is ocrevustum:-)

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    3. OMG - http://www.trademarkia.com/ocrevus-86205182.html . They has OCREVUS since last year and they didn't tell us? It's such a great name.. rolls right off the... Weird name aside, I'm hoping for news on the RRMS filing too.

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    4. Ocrevus!? That was my maternal grandmothers name from the old country. What a coincidence.

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  7. I'm don't understand this response. (Sorry). I understand they picked younger patients. If there are enough who never have enhancing lesions, wouldn't that be covered in this afternoon's talk. How did the drug affect any with no enhancing lesions yet have active PPMS (meaning progression of disability)? This drug will go in the market and patients will not know?? Sorry doctors but you need to speaking out about this. Not just on this blog, but neurologists everywhere. Especially if this fastrsck process does not provide satisfactory answers about risks. Patients deserve data regarding both sides of the risk-benefit calculus.

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    1. In the rituximab trial the people responding the best were younger people with short disease duration and it was found that people with active disease (meaning new MRI lesions) were responding.

      So in the PPMS trial they loaded it up with young people (below 55) and short disease duration (who are more likely to have lesions and about 30% of people had gadolinium lesions in the trial.

      The PPMS population actually has about 15% of gadolinium activity, so in the trial there wwere twice as many people recruited who could respond. So the trial was loaded to show a positive response and that is what happened but the question is does it really work in people who are not having new lesions. Based on all other trials we would think no. However are B cells the drivers of progressive MS. Also why did gilenya fail. The age was certainly different.

      The question is how are the results dress edup and will it convince the regulators to say yes...use it for every one with PPMS or will they say it is most likely to work in people with active (MRI positive) MS. This is such an obvious question unless someone has slpped the assessors a few bob it will be surprising if this question is not asked. If it is not asked some butt needs to be kicked!!

      In the title it says they will relate activity to people with gadolinium enhancing lesions. They are responders. However there may be people who had gadiolinium lesions before or after their scans.

      I am sure there will be people at ACTRIMS that can tweet about this presentation, it is bound to catch the medias eye

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  8. "Among other parameters, the B cells of patients with MS produced elevated levels of IL-6."

    And many more info on IL-6
    "Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges; doi:  10.1177/1756285612474333


    "These data identify IL-6 as an important target to modulate autoimmune responses and chronic inflammation."

    "IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells"; doi: 10.1073/pnas.0809850105

    I dind't find any info on how ocrelizumab acts on IL-6.
    Only about the interaction of B-cells and IL-6.

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  9. When will DR's be able to prescribe Ocrevus for patients AND should we harvest stem cells before taking?

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