Staying With Rituxan Rather Than Switching to Ocrevus

The latest disease-modifying therapy, called Ocrevus (ocrelizumab), was approved in March 2017 for relapsing and primary progressive forms of MS. Ocrelizumab works differently than other DMTs for MS in that it selectively depletes B-cells. B-cells are a type of white blood cell that develops antibodies in response to specific antigens, a process which helps the immune system to fight invaders. However, abnormal B-cells may mistakenly produce autoantibodies that contribute to autoimmune diseases such as multiple sclerosis, rheumatoid arthritis (RA), lupus, or scleroderma.

Ocrevus is very closely related to the drug Rituxan (rituximab) which is used to treat certain autoimmune diseases, such as rheumatoid arthritis and myasthenia gravis, as well as cancers like non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Both therapies work in the same way to alter the immune system. Rituxan is also commonly used off-label to treat MS, and I have personally used it since 2009.

Ocrelizumab specifically targets and destroys CD20+ B-cells in a way that serves to lower the immune system. Studies of ocrelizumab demonstrated that it could reduce relapses by 46 to 47 percent in people with relapsing MS compared to treatment with subcutaneous interferon beta-1a. People with primary progressive MS (PPMS) who received ocrelizumab were 24 percent less likely to experience disability progression than those who received placebo in a clinical study.

Ocrelizumab is an intravenous infusion therapy which is delivered twice a year in an infusion center or doctor’s office. The first dose is divided in half and given as two separate infusions, two weeks apart. Pre-medications, such as corticosteroids and an antihistamine, are given in advance to reduce the risk of infusion-related reactions that may include itchy skin, hives, coughing or wheezing, throat irritation, flushing, shortness of breath, dizziness, or fatigue. Since ocrelizumab weakens the immune system, patients are at greater risk of developing infections. Additional risks include reactivation of the hepatitis B virus and progressive multifocal leukoencephalopathy.

The decision to switch treatment or not

The MS community has received ocrelizumab with excitement and open arms. I personally know several people who have either switched to Ocrevus already or are considering it. Several factors come into play when making treatment decisions, including comparing efficacy, side effects, impact on lifestyle, and insurance coverage. Twelve years ago, MS patients would choose a treatment and stick with it, even if their disease remained active. Now, patients have options and may switch DMTs when their disease fails to reach NEDA (no evidence of disease activity).


Like many people living with multiple sclerosis, I am determined to do all I can to slow down the disease. Although I might not always exercise as much as I should or I might indulge in rich food on occasion, I still try to focus on healthy lifestyle habits and reduce stress. An important part of fighting this disease for me is to consistently use a disease-modifying therapy.

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Why I Am Not Considering Ocrevus?

Ocrevus Receives Breakthrough Therapy Designation

Genentech and Roche announced that the Food and Drug Administration has granted Breakthrough Therapy Designation for the investigational medicine ocrelizumab (Ocrevus™) for the treatment of people with PPMS. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening disease and for which preliminary clinical evidence suggests that the drug may demonstrate substantial improvement over existing therapies. Remember that PPMS has no approved therapies.

Breakthrough Therapy Designation was granted to ocrelizumab based on positive results form a pivotal Phase III study (called ORATORIO) which showed treatment with ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo in patients with PPMS. Top-line results were of ORATORIO were presented at the 31th ECTRIMS conference in October 2015.

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FDA Grants Breakthrough Therapy Designation to Treatment for Primary Progressive MS

Positive Trial Results for Ocrelizumab in Primary Progressive MS

After lots of hype and buildup ahead of the conference, the pharmaceutical company Roche-Genentech finally revealed a bit more than simply “positive results” from three pivotal Phase III studies of the experimental MS therapy ocrelizumab in relapsing MS and primary progressive MS (PPMS). While relapsing MS has 13 approved therapies and other treatments which are used off-label, such as rituximab, effective treatment for PPMS has continued to be elusive.

What is ocrelizumab?

Ocrelizumab is a humanized (10 percent mouse, 90 percent human-derived) monoclonal antibody designed to target a selective group of immune cells - CD20+ B-cells - which have been implicated in the damage of myelin, the fatty substance that protects nerve cells and helps to speed the transmission of nerve signals throughout the body. In clinical trials, ocrelizumab 600 mg was administered by intravenous (IV) infusion every six months, given as two 300 mg infusions spaced two weeks apart in the ORATORIO trial, while repeat rounds in the OPERA I and II trials were given as a single 600 mg dose infusion.

Ocrelizumab works in the same way as rituximab (Rituxan), a chimeric (100 percent mouse-derived) monoclonal antibody that attaches to CD20 cell surface proteins and causes certain B-cells (but not stem cells or plasma cells) to self-destruct. Rituxan is used to treat rheumatoid arthritis (RA), non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), granulomatosis with polyangitis (GPA) and microscopic polyangitis (MPA). Rituxan is also used off-label for a number of other autoimmune diseases including MS and neuromyelitis optica (NMO). Patents protecting Rituxan (jointly marketed by Genentech and Biogen) from generic competition begin to expire in 2015.

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Is Ocrelizumab The Next Game-Changer in MS Treatments?

Ocrelizumab in Multiple Sclerosis

Many news stories are flooding my Google Alerts due to ECTRIMS which occurred last week.  Many abstracts to read and discuss, so little time.

One treatment which I'm keeping my eyes on is ocrelizumab (which is basically the humanized version of rituximab).  Studies of ocrelizumab in rheumatoid arthritis were halted last March due to deaths in the Phase III trials.  Studies of ocrelizumab in lupus have also been halted.

I'm personally interested in following the success of ocrelizumab just so that MS patients might be able to try it on-label, as opposed to attempting to use rituximab off-label.  But if it proves to be unsafe, then we should all stop to weigh the benefits/risks (as we should with all treatment choices).

I'm including one brief article below regarding this new information.  Please do follow the links at the end of this article for more information.  The one statement which gives me a little twinge in the stomach refers to the MS market quickly growing to $13 billion.  Just a couple weeks ago, it was estimated at $7 billion.

While I do not believe in conspiracies to keep us "sick", I must concede that we represent a lucrative market.  Too many dollar signs floating around.  Sigh. 

Patient death mars promising MS results in PhII ocrelizumab trial
By John Carroll

Just five months after risk factors forced Roche and Biogen Idec to scuttle a program to develop ocrelizumab for rheumatoid arthritis, researchers are touting new mid-stage data showing that MS patients on the drug experienced a reduction in relapses and brain lesions. But they also noted that one person died in the trials and that patients in the drug arm of the trial experienced a higher rate of some side effects than the patients in the placebo arm.

The patient died from systemic inflammatory response syndrome, which is sometimes caused by infection. But the researchers said they could find no evidence of opportunistic infections in the study. Infusion site reactions among patients taking two different doses of the therapy were significantly higher than the placebo group, though researchers reported that the reactions were largely mild to moderate and tapered off during the second infusion.

MS is one of the hottest fields in drug development. Pharma companies are zeroing in on a market with high unmet medical needs, with analysts forecast MS drug sales are quickly headed to $13 billion.  Roche and its partner say they are ready to

"We are strongly encouraged by these data and the possibility that ocrelizumab could become a new option for patients with MS," said Dr. Hal Barron, Roche's chief medical officer. "We believe in the potential of ocrelizumab and look forward to exploring it further in the final phase of clinical development."

Patient deaths during the Phase III RA trial doomed the program. The two companies shut it down, just as they did for lupus. Ocrelizumab had been one of the brightest starts in Roche's pipeline, but its potential blockbuster status has dimmed considerably in recent months.

- check out the Roche release for more
- read the Reuters story

Related Articles:Roche, Biogen shutter blockbuster ocrelizumab arthritis program
Infections and deaths force Biogen, Roche to suspend blockbuster program