Could Genentech’s Ocrelizumab Become the First Effective Primary Progressive MS Therapy?

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Genentech, a leading biotechnology company and member of the Roche Group, recently announced promising results on a pivotal Phase III clinical trial (ORATORIO) assessing its investigational therapy ocrelizumab as a treatment for patients with primary progressive multiple sclerosis (PPMS).

Multiple sclerosis (MS) is a chronic, progressive neurodegenerative disorder that results from an abnormal attack on the central nervous system (brain, spinal cord and optical nerves) by the body’s own immune system, causing inflammation and damage to the myelin layer that covers and protects neurons, resulting in motor function impairment, irreversible neurological disability and paralysis. There is no cure for MS, and it is estimated that more than 2.3 million people in the world suffer from the disease.

Progressive forms of MS are estimated to affect at least 40% of all MS patients and are characterized by a gradual, steady progression of disability, leading to impaired vision and walking, pain, fatigue, incontinence and cognitive changes. Patients usually have a poor response to treatment and there is little or no recovery. According to the National Multiple Sclerosis Association, progressive forms of the disease include Primary Progressive Multiple Sclerosis (PPMS), which is diagnosed in 10% of all MS cases and is characterized by a steady progression of the disease from the time of diagnosis, and Secondary Progressive Multiple Sclerosis (SPMS), where patients initially experience a relapsing-remitting MS phase (RRMS) of neurological dysfunction that later evolves in approximately half of the cases into a secondary progressive disease.

Ocrelizumab is a humanized, monoclonal antibody against immune B cells that express CD20 proteins at their surface. These cells are thought to be a key contributor to the myelin and neuron damage in MS patients.

The ORATORIO (NCT01194570) study is a multicenter, double-blind, randomized, placebo-controlled, Phase III clinical trial developed to evaluate the efficacy and safety of ocrelizumab (administered intravenously as two 300 mg infusions two weeks apart) in 732 patients with PPMS.

Researchers now report that the ORATORIO study has met its primary endpoint, as ocrelizumab treatment was found to significantly reduce the patients’ clinical disability progression in comparison to a placebo. In the trial, clinical disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) sustained for a period of at least 12 weeks.

In terms of safety, the occurrence of adverse events in the patient group given ocrelizumab was similar to the one in the placebo group. The most common adverse events reported were mild-to-moderate reactions related to the infusion.

“People with the primary progressive form of MS typically experience symptoms that continuously worsen after the onset of their disease, and there are no approved treatments for this debilitating condition,” said the chief medical officer and head of Global Product Development, Dr. Sandra Horning in a press release. “Ocrelizumab is the first investigational medicine to show a clinically meaningful and statistically significant effect on the progression of disease in primary progressive MS.”

The safety and efficacy of ocrelizumab has also been evaluated in Phase III clinical trials (OPERA I and OPERA II) in patients with relapsing forms of MS (either RRMS or SPMS with relapses), having yielded promising results, as ocrelizumab treatment significantly reduced the annualized relapse rate, the progression of clinical disability assessed by EDSS, and the number of MS lesions in the patient’s brain in comparison to IFN beta-1a treatment.

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Together, the results of these three clinical trials support the theory that immune B cells play a key role in MS and that ocrelizumab can be considered an effective therapy for the disease.

The ORATORIO trial results will be presented at the upcoming 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain, as a late-breaking abstract by Dr. Xavier Montalban, chair of the Scientific Steering Committee of the ORATORIO trial and professor of Neurology and Neuroimmunology at Vall d’Hebron University Hospital and Research Institute, Barcelona, Spain. The presentation is scheduled for Saturday, October 10th (8:52 – 9:03 am CET, Abstract #228).

Results from the Phase III trials OPERA I (NCT01247324) and OPERA II (NCT01412333) in relapsing forms of MS will also be presented at the Congress by Dr. Stephen Hauser, 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. The presentation is scheduled for Friday, October 9th (14:40 – 14:52 pm CET, Abstract #190).

Genentech is currently planning to obtain marketing authorization for ocrelizumab as an approved therapy for both PPMS and relapsing MS, and plans to submit data on the ORATORIO and OPERA I and II trials to the U.S. Food and Drug Administration (FDA) in early 2016.

Multiple Sclerosis News Today, from the BioNews Services group, plans to cover the ECTRIMS 2015 Congress and offer the readers real-time data and updates as they are disclosed at the meeting.

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  1. Maggie says:

    Please, please let this drug really work and have mild side effects. Progressive MS is nothing short of miserable and under diagnosed.

    • Maggie says:

      Genentech says the incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was also similar to placebo.

      Genentech plans to pursue marketing authorization for ocrelizumab in relapsing MS and in PPMS. Data from the OPERA I and II studies and from the ORATORIO study will be submitted to the U.S. Food and Drug Administration in early 2016.

      Sounds very promising with little side effects. There’s hope in the horizon but I still hold the most hope through regenerative medicine in the future. We also half to elect the right people into office. I, myself, think Bernie Sanders will get this done for us. Us meaning all suffers due to chronic debilitating sometimes fatal conditions. I think the GMO food we eat has a lot to do with these climbing numbers of cancer, auto immune, inflammatory etc… diseases. I wouldn’t doubt if Monsanto is in bed with Big Pharma and the FDA. I’m not a conspiracy theorist but it just makes sense the more you do your research.

  2. Patricia Black. says:

    I have secondary progressive Multiple Sclerosis and have lost all my independence I hate this disease. I manage to walk with the help of a frame but I cant go out without a scooter. I wish I could go on a trial, I would do anything to get well again.

    • betty fertig says:

      3/24/2016 reply to patricia black. i have primary progressive ms, and like you have lost all my independence. i had to give up driving, which i love to do. i have a cane, a rollator, and a walker. i really hate this disease, too. i have a very supportive family, but until you have ms, they will never understand.

  3. Sherry Adams says:

    I have PPMS and sometimes I feel like I am losing it! It has mostly effected my cognitive function, mathematical skills and word skills. I can never locate the right words, or I say things that come out wrong often to the embarrassment of others. I never even realize what I said wrong. I stop mid sentence altogether forgetting the words or what I was even saying. My family is kind about these things but I have become a loner when I use to be the life of the party. Thank God for spell check I can’t spell most of the time and have forgotten punctuation altogether. I have seizures caused by my MS and for an RN forced to retire due to PPMS I want a cure like years ago!!! I’m way too young to be retired.

  4. William Wezel says:

    I have PPMS for some 16 years now. Walking with a stick or walking frame is the only way I can get around. Getting on a bus, train or plane ( with stairs ) is impossible.
    My eye sight has been reduced by some 30 to 40%

    When and how will this new drug be released?

  5. David Corke says:

    I am an MS patient and it is getting worse every day, if there is any testing that you need to do I am willing to help.I used to go on runs every night but now I have a job to walk across the room with a frame.Wishing you all the luck in the world with your research and hope to hear from you soon.

  6. Winnie says:

    Let’s all pray hard for this drug to be a success & available to all of us very very soooooooo !!! And yes, at an affordable price!

  7. Renee says:

    Oh my God, I just read the breaking news on this new drug and I nearly cried. Do we with PPMS dare to hope that there might actually be something for us on the horizon? PPMS is such a cruel disease. I have had it for approx 13 years and it has been a slow decline and paralysis and has taken away a lot of my quality of life. Please please let this be IT and that it be available in my country and affordable.

  8. Maggie says:

    Just FYI: What is “acceptable risk” for an MS patient taking Ocrelizumab therapy?

    From 2015. There were 6 deaths associated with infections in the RA phase III trial.

    There were 5 deaths associated with serious infections in the Lupus phase III trial.;jsessionid=6715BA3BC3CBCEB00677548A44DE6C77.f02t03?v=1&t=if74oiub&s=f1b0440dbdec19dbfae12216c503aeba8c47e403

    There was a new press release out from Biogen regarding the termination of the Phase III trial of its drug, ocrelizumab.

    “Swiss drugmaker Roche AG and Biogen Idec Inc. are discontinuing development of ocrelizumab in patients with rheumatoid arthritis (RA), after an infection-related safety signal was observed in Phase III testing, resulting in the death of some patients. Results from the program will be made available at a medical forum, the companies said, without divulging the specific type of infection or the number of affected study patients.

    Roche and Biogen have said that the infections were serious, some of which were fatal, and others were opportunistic infections.The FDA had placed a clinical hold on the studies prior to the companies’ ultimate decision to stop development in RA. Last year Biogen had stopped its Phase III program of ocrelizumab in lupus patients.
    The market reacted with little surprise to the latest news, with shares in the two companies barely rattled by the news of the folded ocrelizumab program in the RA setting.
    Biogen shares (NASDAQ:BIIB) dipped 24 cents, closing at $50.46, while Roche Holding was down slightly on the Swiss stock exchange.

    “A Phase II study of ocrelizumab is ongoing in patients with relapsing remitting multiple sclerosis, and data from that study will be submitted for presentation this fall at the European Committee for the Treatment and Research in Multiple Sclerosis conference in Sweden.”

    Even with the knowledge that this drug has killed…the trial continues in MS patients. Why? Who decided this was acceptable risk for MS patients??? One only needs to look to investor publications for the answer:

    This is from the Wall Street Journal yesterday…remember, the WSJ is VERY CONCERNED with MS patients’ safety!

    “Roche said Tuesday that ocrelizumab’s phase II trials in treating patients with relapsing remitting multiple sclerosis are continuing. But some analysts doubt the drug will come to market as the recent safety issues are likely to put the U.S. Food and Drug Administration on alert.

    Ocrelizumab was expected to reach peak sales of up to $2 billion and was partly considered to be a line-extension drug for Roche’s cancer medicine Rituxan, one of the company’s best-selling products, which will lose patent protection in 2015.

    The recent trial failures have curbed the drug’s sales potential and some analysts now expect that if ocrelizumab’s multiple sclerosis indication passes all regulatory hurdles, it will generate less than $1 billion in annual sales.”

    Less than one billion?? That is really so sad. It could have made 2 billion IF IT DIDN”T KILL PEOPLE!!!

    “Roche and Biogen are continuing a phase 2 trial testing ocrelizumab in multiple sclerosis patients. That’s probably not a complete waste of money. Given the relative severity of that disease, multiple sclerosis drugs can have worse side effect profiles than rheumatoid arthritis drugs.”

  9. I was in the trial..It is over and now is in the “open label” phase..
    I thought I was getting the placebo because I was getting worse, but I was getting the drug I just found out. I have PPMS and still getting worse.

  10. Colin Campbell says:

    Being aged 55 it is utterly ridiculous that I not be immediately given ocrelizumab at my own risk. I am considering voluntary assisted suicide so would rather help others by taking ocrelizumab NOW. Makes far more sense to try ocrelizumab as I literally have nothing to lose.

  11. H.Crawford says:

    I’m only 48 and this horrible disease is making my life a nightmare. I pray this med works as well as they say. At this time I would rather be with God than live this miserable life. Please hurry the release.Thanks

  12. Geoff Flynn says:

    HSCT works just fine with progressive. I’m PPMS and had HSCT in Oct 2015, haven’t felt this good in years. Pharmaceutical companies are not a fan since it doesn’t require taking drugs for the rest of your life. It gets very little support from the MS establishment but you can’t argue with the results. I see many comments from desperate progressives. I know the feeling since I received no help from the MS clinic or “experts” in general. Unfortunately you have to do your own research. I encourage you to look into HSCT.

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