Thursday, March 30, 2017

Ocrevus: Prominent MS Clinic Issues Cautionary Statement

 

On March 28, 2017, the new MS drug Ocrevus was approved for both relapsing MS and progressive MS, becoming the first drug to achieve FDA approval for the progressive form of the disease.


One of the nation's leading multiple sclerosis clinics, the International Multiple Sclerosis Management Practice (IMSMP), today published a statement on their website regarding Ocrevus and its possible link to cancer and opportunistic infections (click here). Here is the clinic's statement in full:


Ocrelizumab (OCREVUS™), an anti-B cell therapy has been approved by the FDA as of March 28th 2017, for the treatment of Relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). This treatment is highly effective for RRMS, based on the data from the Phase III clinical studies. It is also the first drug approved for use in PPMS. At IMSMP/TISCH we have used Rituximab, a similar anti-B cell treatment, for the past 16 years with great success. It is because of the effectiveness of this therapy (Rituximab) we were able to persuade Medicare to cover the costs of this therapy in New York.

Rituximab, however, is NOT approved by the FDA for use in MS. At our center we use it as an off-label drug. This unfortunately can require several weeks to obtain approval from insurance carriers and often approval may be denied.

Therefore, the approval by the FDA of Ocrelizumab, which should have almost identical anti-B cell activity to Rituximab, appears to be good news for MS patients. However, there are some serious concerns with Ocrelizumab that patients need to be made aware before they consider this therapy. First, in the RRMS trial, there were 9 patients who developed various malignancies within three years of taking Ocrelizumab (4 patients within the first 2 years and 5 patients in the following year). This is alarmingly high considering that these patients were mostly in their third decade of life and had no previous history of cancer. In the trial for PPMS patients, 13 patients developed cancer within the three years of taking Ocrelizumab (11 in the first two years and 2 additional cases in the following year). This means that more than 1 in 50 patients developed cancer within three years of taking Ocrelizumab among the PPMS patients. These risks of malignancy associated with Ocrelizumab are not seen with Rituximab (more than a thousand patients just at our center since 2001 and several hundred thousand worldwide). This risk of cancer with Ocrelizumab is not explained at present and the magnitude of the problem cannot be defined, as the medication has not been given for a period longer than 3 years.

There are also additional concerns with Ocrelizumab, such as the risk of life threatening infections which caused the trials in patients with Rheumatoid arthritis and SLE to be halted in 2010.

Although, it is indeed progress that the first medication for PPMS has been approved, the patients should be fully informed of its’ potential risks. For patients who can obtain Rituximab, it would be safer to continue with this therapy, until with time, we are better able to advise patients about the risks associated with Ocrelizumab.

The IMSMP is the clinic at which I receive my MS care, and I am personally acquainted with all of the medical professionals who work there. I know firsthand that the staff is wholly dedicated to the well-being of MS patients and that they wouldn't issue such a statement without diligent consideration.

Having said that, in the interest of fairness, I reached out to Genentech, the makers of Ocrevus, for a statement on the IMSMPs comments on their drug.  I received the following response from Genentech spokesperson Kimberly Muscara:

The FDA approved Ocrevus as an important new medicine for people with relapsing forms of MS and the first and only treatment for people with primary progressive MS. Genentech encourages healthcare providers to prescribe medicines as per their label and indication, and as a company we cannot comment on off-label usage. As you know, Rituxan is not an FDA approved medicine for multiple sclerosis and has not been rigorously investigated in Phase III clinical trials.  

Additionally, Rituxan and Ocrevus are different molecules in structure and how they interact with the immune system. 

In controlled clinical trials, there was an imbalance in malignancy. An increased risk may exist. The incidence of malignancy was within background rates, and to date continued follow-up in the open-label extension study has not shown increased risk of malignancy with longer time on Ocrevus. Patient safety is very important to us at Genentech and we are committed to conducting long-term post-approval safety studies on Ocrevus.

Muscara also noted that some patients have been on Ocrevus longer than three years, as enrollment in the phase III trial started in 2011 and a number of patients have remained on the drug in extension studies. It should also be noted that Ocrevus is the first anti-B cell therapy approved for use in MS, and that the research that led to the drug has profoundly shifted the thinking of many MS researchers.


In the days since Ocrevus received FDA approval, I've seen and read countless articles and reports in the mainstream media heralding the drug as the latest medical miracle. While Ocrevus may indeed prove to be a major step forward in the treatment of MS, there are legitimate reasons to exercise discretion when considering this new drug. I'd urge all patients to have well-informed conversations with their neurologists before embarking on any new MS treatment. Each MS patient has their own set of priorities and tolerance for risk. What is completely unacceptable for one patient may be well within another's comfort zone.


I wrote a thorough review of the complicated history of Ocrevus (click here), and also conducted a lengthy interview with one of the drug's researchers, Dr. Peter Chin (click here). I hope that patients can glean valuable information from both of these articles.


Remember, the patient-doctor relationship MUST be a partnership, not a dictatorship, especially when it involves a chronic progressive illness such as multiple sclerosis. Arriving at any treatment decision is a multifactorial process, and as patients suffering from a potentially devastating disease we owe it to ourselves to fully participate in all decisions related to our ultimate well-being. Knowledge is power, my friends, use it wisely.

18 comments:

  1. It could open up clinical trials and FDA approval for Rituximab? I'm taking an RRMS drug that is doing okay at slowing MS progression on my MRIs right now. The thought of a drug that's has worked on PPMS is a beacon of hope, but with a cancer history in my family, I'm not sure I'm looking to change my treatment just yet. I will talk to my neurologist about it though. Thanks for the post!

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    1. Doubtful that there will be any trials of Rituxamab in ms. No money to be made from them by the pharmaceutical companies, and they're the ones that run the late stage clinical trials. The price of these trials is so high that the pharmaceutical companies are pretty much the only entities that cannot afford them these days. Crazy, right?

      Please check out the commentary that I wrote on ocrelizumab, which is linked to in the above article. It includes links to a retrospective study done in Europe on the use of Rituxan in MS patients. Shows it to be very effective. Interesting reading.

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  2. Interesting information. Thanks for doing the research! Can you post a link to the original statement from the IMSMP?

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    1. I just added a link to the statement, it's now in the paragraph preceding the text of the actual statement. Thanks for reminding me, meant to include a link when I first wrote the post.

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    2. Hello I have had MS for.almost 19 years now. I.was on betaseron copaxone ang gilenia these drugs did not work for me. Now I an on aubagio, which is working but I have heard that Lemtrada is much better. Once the infusions are complete then you are finished with all the MS drugs. Do you have an opinion on this medication and or any additional information?

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    3. Hi,

      Lemtrada is a very good drug, but it does have some very serious potential side effects. About 50% of patients taking it get secondary autoimmune diseases, and there is the risk of a deadly blood disorder.

      Certainly a drug to consider, but it warrants having some very serious talks with your neurologist. You don't mention what type of MS you have, but at this stage I'm guessing it's SPMS? I believe Lemtrada is mostly used on patients with very active relapsing remitting MS, who have enhancing lesions. Of course, doctors are free to prescribe it to whichever patients they choose…

      Hope this helps. My best advice is to discuss this with your neuro…

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  3. Meet the rock and the hard place.
    With MS and other autoimmune diseases running in my family, everyone who developed an autoimmune disease went on to develop the big "C". The stem cell solution can't come soon enough.

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    1. Stem Cell solution is already here! Just Google HSCT. My hubby had it in Chicago's clinical trial 6 years ago. It STOPPED his MS & he's had reversal of most of his previous symptoms. HSCT is also being done in Russia, Mexico, Philippines & more.

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  4. Mark,
    Thank you very much for keeping us well informed as always. I don't know what I would do if I didn't have access to your blog for all these years. The way you "digest" and summarize information, is priceless...

    As for this one, I thought I had seen an information that significant majority of those cancers were breast cancers, am I right?


    Thank you again and looking forward to your next post

    Dragana��

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    1. Yes, I believe many of these cancers were breast cancers.

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  5. Thank you Marc for following the research and development for us readers. I myself is on Rituximab, but unfortunately I am progressing (without a definitive diagnosis). As you note it is extremely important to be well informed when you meet your doctor. Thanks again. Johan

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  6. "Rituximab had been tested before in MS with notable success. However, as we explained before, that study did not lead to a phase III trial due to commercial interests. Then its humanized version was tested expecting more safety and tolerability. But it happened that, paradoxically, Ocrelizumab turned out to be less safe." Https://neuroimmunology.wordpress.com/2011/11/03/rituximab-vs-ocrelizumab-in-multiple-sclerosis/

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    1. Rituximab use comes with a risk of developing PML. I'll be curious to see if Ocrelizumab also shows this risk with longer safety studies.

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  7. How many were in these studies?

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    1. There were about 1600 patients in the relapsing MS studies, and about 700 in the progressive MS trial.

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  8. Thanks so much for the info I'm new at this so anything I can learn HELP'S.

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  9. Correction: Rituxan does NOT come with high risk of pml. Successful since 2004 for use on MS patients. No MS protocol has produced pml. Even used at higher doses for cancer pml risk 1/25000.

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