Ocrelizumab: Could Genentech/Roche’s Experimental Drug Be the First Effective Progressive MS Therapy?

Ocrelizumab: Could Genentech/Roche’s Experimental Drug Be the First Effective Progressive MS Therapy?

Roche announced positive results for three pivotal Phase III studies of experimental MS therapy ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis (PPMS) patients at this year’s ECTRIMS 2015 conference. The results, particularly for treating PPMS, indicate that the novel therapy may represent a viable therapeutic option for progressive forms of the disease.

Multiple sclerosis (MS), a progressive neurodegenerative disorder, has no cure and is estimated to affect more than 2.3 million people worldwide. Relapsing Multiple Sclerosis is the most common type of MS, affecting approximately 85% of all patients with the disease. Primary progressive MS (PPMS) is characterized by escalating worsening symptoms and affects 1 in every 10 MS patients. No approved treatments currently exist for PPMS.

Ocrelizumab, an investigational, humanized monoclonal antibody was designed to target a selective group of immune cells — CD20-positive B cells — which have been shown to damage myelin, the protective layer that covers neurons and that once destroyed leads to motor function impairment, irreversible neurological disability and paralysis.

The therapy was tested in three major clinical trials – OPERA I, OPERA II and ORATORIO. The OPERA I and OPERA II studies tested ocrelizumab in patients with relapsing MS, which showed increased efficacy in reducing three key markers of disease activity when compared to interferon beta-1a (Rebif®), a well-established MS therapy.

The ORATORIO study focused on patients with PPMS where ocrelizumab significantly reduced disease progression — particularly patients’ disability — for at least 12 weeks (primary endpoint), when compared to a placebo control group. Additionally, ocrelizumab achieved positive results in other parameters (secondary endpoints), including reducing the time required to walk 25 feet, the volume of chronic inflammatory brain lesions and brain volume loss.

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Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development commented on ocrelizumab’s major breakthrough: “The results of these three pivotal trials have the potential to transform the treatment of MS. Ocrelizumab is the first investigational medicine to significantly reduce disability progression in people with relapsing MS and people with primary progressive MS – a form of MS with no approved treatments. We are eager to work with regulatory authorities to bring this investigational medicine to the MS community as soon as possible.”

Stephen Hauser, M.D., Chair of the Scientific Steering Committee of the OPERA studies and Chair of the Department of Neurology at the University of California San Francisco School of Medicine added, “These results redefine our understanding of MS by highlighting the central role of the B cell. The findings may also encourage the MS community to look more closely at earlier treatment of the disease. Currently, many doctors reserve what are considered highly effective MS medicines until a patient’s disease becomes more advanced. Patients and their doctors need new treatment options that offer the potential for greater efficacy than a standard-of-care interferon with a similar safety profile.”

Xavier Montalban, M.D., Ph.D., Chair of the Scientific Steering Committee of the ORATORIO study and Professor of Neurology and Neuroimmunology at Vall d’Hebron University Hospital and Research Institute, Barcelona, Spain also noted, “This is an important moment for the MS community. For decades, trial after trial has failed to show the benefit of any medicine for people with primary progressive MS. Now, for the first time, we have a positive Phase III study result for people with this debilitating form of the disease.”

Roche will now seek marketing authorization for ocrelizumab in both relapsing MS and PPMS.

9 comments

  1. Missy says:

    So THAT’S why the big guns dropped heir patent challenges against Ampyra – who needs generic dalfampridine anymore? This is great news for MS sufferers.

  2. LYNNE HEAL says:

    NOT one MS drug has ever cured MS and never ever will either . Too many are making profits, shares and commissions from MS drugs alongside very high salarys . Billions upon billions .Awaits for someone to actually realize whats been going on for decades . Asks always how many have died on MS drugs . No one yet has done the data on. R.I.P to everyone whos no longer with us and cannot speak up after sadly passing away on MS drugs

  3. LYNNE HEAL says:

    From 2015. IMPORTANT TO UNDERSTAND—the trials with serious infections and deaths reported were at 52 and 48 weeks.
    The MS trial was ONLY 12 WEEKS.

    There were 6 deaths associated with infections in the RA phase III trial.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911947/
    There were 5 deaths associated with serious infections in the Lupus phase III trial.
    http://onlinelibrary.wiley.com/store/10.1002/art.38037/asset/art38037.pdf;jsessionid=6715BA3BC3CBCEB00677548A44DE6C77.f02t03?v=1&t=if74oiub&s=f1b0440dbdec19dbfae12216c503aeba8c47e403

    HOW MANY MORE DEATHS of MS participants in the trial would be reported if patients on Ocrelizumab were followed for a year, instead of 3 months??!!

  4. Alice Bager says:

    FOR SOME REASON, many tends to underestimate the risks with Ocrelizumab ( Ocrevus ) – it is far to much blue sky (sorry) opinions aired about this, to my view, risky MS-agent.

    APART FROM ALL these cancer cases in the ORATORIO / PPMS trial (2.3% vs 0.8%) and also worrying 6 cases of breast cancer vs 0 in placebo – if you include the RRMS trial (Opera I/Opera II), it would be good to look at the history of this Ocrelizumab – its footprints in the past.

    OCRELIZUMAB WAS HALTED in 2009/2010 both in Lupus and in RA due to several fatal deaths. It is by the way, very little talk about this in the context of the hype around, at least among some, Ocrelizumab in MS (rrms and ppms) … I wonder why this silence as to previous safety footprints with ocrelizumab ( Ocrevus ) …(?!)

    THERE WERE 6 DEATHS associated with infections in the RA phase III trial.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911947/

    FURTHERMORE, THERE WERE 5 DEATHS associated with serious infections in the Lupus phase III trial.
    http://onlinelibrary.wiley.com/doi/10.1 … 38037/full

    Both studies were halted due to these deaths using Ocrelizumab.

    ON OF THE FEW that really highlights the high risks with this Ocrelizumab is this professor Mark Freedman, who, for instance, did this statement at an interview at Ectrims 2015 – he starts talking about Ocrelizumab at the 3:50 mark of the video.

    https://www.youtube.com/watch?v=EzM1NbZ … e=youtu.be

    MY POINT:
    Given Ocrelizumabs history, I think it is about time to acknowledge that this agent comes with great risks, given its bad safety footprints both in previous studies in RA and Lupus, and now lastly in MS – referring then firstly to all these malignancies.

    Yes it appears to have a good efficacy towards halting relapses, but at what cost ? Roche wants of course to market this agent for a broad patient population to earn money. That is only natural wish for a business company.

    But to my opinion, use of Ocrelizumab could only be an option for patients who is willing to take the risks and have highly active MS-disease.

    And as professor Mark Freedman states in the above interview, what will happen in the long run when you suppress or deplete the B-cells so heavily as ocrelizumab dose …?

    I JUST WISH THAT we could have a more balanced discussion about risks and benefits. So far, to much of the debate is focused on the positive effects, but not so much is mentioned about Ocrelizumabs (OCREVUS) risks.

    Professor Mark Freedman is one of the few that stands up and air a more balanced view on risks and benefits with regard to this Ocrevus (Ocrelizumab).

    Conclusion:
    It is a about time to have a more balanced discussion with regard to risk and benefits

    • Tim Bossie says:

      There is no doubt that this drug comes at great risk. Thank you for the extra information and we hope that as technology and new practices are made available drugs like these will get better and without the terrible risk and effects.

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