#AANAM – Greater Exposure to Ocrevus Means Less Risk of Disability Progression in MS Patients, Study Contends

#AANAM – Greater Exposure to Ocrevus Means Less Risk of Disability Progression in MS Patients, Study Contends

Higher exposure to Ocrevus (ocrelizumab) is associated with greater immune B-cell depletion in the blood, and lessened risk of disability progression in patients with relapsing multiple sclerosis (MS) and primary progressive disease (PPMS), according to new research.

The study supporting that finding, “Pharmacokinetics, Pharmacodynamics and Exposure-Response Analyses of Ocrelizumab in Patients With Multiple Sclerosis,” was presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, held in Philadelphia May 4–10. The data were presented by Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco (UCSF).

Ocrevus is an approved treatment marketed by Genentech for patients with relapsing MS and those with PPMS. The therapy is a humanized monoclonal antibody that targets specific immune cells — CD20+ B-cells — and is administered intravenously (600 mg every six months).

In the study, researchers used Phase 2 and 3 clinical trial data to characterize Ocrevus’s pharmacokinetics — its absorption, distribution, metabolism, and excretion in the body — and pharmacodynamics (how the body responds to the therapy).

The team also analyzed exposure-response associations in terms of clinical effectiveness — as assessed through the annualized relapse rate, and 12- and 24-week confirmed disability progression (CDP) — and safety, namely the associated serious adverse side effects, serious infections, and infusion-related reactions.

Researchers created a model accounting for time-dependent Ocrevus’ clearance and patients’ body weight, which accurately described the treatment’s pharmacokinetics in 941 patients with relapsing MS and 482 with PPMS. Exposure to the therapy was 26% higher in patients with relapsing MS under 60 kilograms (kg), and 21% lower in those above 90 kg of body weight versus a 75 kg reference patient.

The data further showed that depletion of B-cells — targeted by Ocrevus —  correlated with the extent of exposure to the therapy. Although the reduction in relapses was found to be independent of exposure in patients with relapsing MS.

Ocrevus also reduced lesions, assessed through magnetic resonance imaging (MRI), to nearly undetectable levels in relapsing MS and PPMS patients.

“Greater B-cell depletion is observed with higher Ocrevus exposure,” Hauser said, while noting that the “annualized relapse rate and MRI [magnetic resonance imaging] outcomes were not exposure-dependent.”

Results also showed that greater decreases in the risk of 12- and 24-week CDP were associated with higher exposure to Ocrevus in patients with relapsing MS and PPMS, when compared to Rebif (interferon beta-1a, marketed by EMD Serono) and placebo, respectively.

“Lower rates of disability progression were associated with higher ocrelizumab exposure and lower median B-cell levels prior to the next infusion,” Hauser said.

Regarding safety, all safety parameters were similar across patients with different exposure to Ocrevus, suggesting that higher exposure does not seem to increase the likelihood of adverse side effects.

Overall, based on the results, Hauser concluded that “higher Ocrevus exposure and greater B-cell depletion may be important for the control of disability progression,” he said.

In an AAN-related Genentech press release, Hauser emphasized: “These are the first data to show that higher Ocrevus exposure is associated with greater control of disability progression without impacting safety. These analyses … create a compelling case for initiating therapy early in the disease course, and provide important information that clinicians can use to inform treatment decisions.”

Also, the fact researchers saw more pronounced effects in patients with higher Ocrevus exposure could indicate “that the current approved dose is closer to the lower part of the dose-response curve,” the team noted, suggesting that greater responses could be seen with higher Ocrevus doses.

However, Hideki Garren, MD, PhD, global head of MS and neuroimmunology at Genentech, is cautious about the idea of “higher dosing, more benefits.”

“It’s important to remember that the most well-characterized dose … is the [approved] 600 milligram dose — 600 mg every six months. In other words, we think that is enough to reduce lesions, reduce relapses, and reduce disability progression. We’ll certainly look into this data and explore more, but what physicians should follow is the well-characterized and proven dose,” Garren said in an interview with Multiple Sclerosis News Today.

Referring to Hauser’s presentation, Garren emphasized that the data show MS patients “need a robust B-cell suppression to see [Ocrevus effect in] disability progression, and again, disability progression, we believe, underlines all forms of MS,” Garren said.

Of note, six of the researchers involved in the study presented at the AAN meeting are affiliated with Roche, which owns Genentech.


  1. Betzaida Vazquez says:

    I use Ocrevus and is excelente. I walk better, i feel more flexible. I walk more and particularly leas spasticity. I love it. My mri is estable no more lesions

  2. Camelia says:

    I had my first infusion in February , and after 15 days I had a painful muscle spasm in hole my right side witch I had it before 5 and half years ago when I diagnosed.I had MRI and shows that I have two new lesions, don’t understand it but I am waiting for next dosage and see what’s the difference.

  3. Leanne says:

    I don’t feel I should necessarily take the data seriously when I get three ads on the same page trying to sell Ocrevus to me.

  4. Charles Dick says:

    researchers seem to be fixated on the B cells, while forgetting that there are also CD20+ T cells. I assume that someone is exploring this as a mechanism to explain the data being collected. A bimodal monoclonal antibody targeting CD20 and CD3 should be investigated. Such a thing could be efficiently engineered by modifying a few residues of each subunit.

  5. AES says:

    I have been on Ocrevus since September 2017 (dxed RRMS in July 2017). After my first dose I did still have one active lesion (down from they many I had prior to starting treatment), but since then I have had no new or active lesions on MRI. I have not had any relapses or disability progression. At least for now, it is working for me.

  6. Bill says:

    I started the infusions in Feb & March 2019, first two were separate infusions. I haven’t noticed any major changes in my progression, as of now. I am very optimistic about Ocrevus!
    I tried stem cell previously and it helped for 8 – 9 months, my dizziness, fatigue and gait improved, too expensive not covered by healthcare. I decided to try OCREVUS, So I might be a little premature with my evaluation on this.

    • Surjit says:

      Hi Bill,
      i am ms patient frOm India suffering frOm this disease since last 18 yrs. Can you please guide me what kind of stem cell treatment and from which place you did this ……..

  7. Barbara M. says:

    What about the age of the MS patient taking Ocrevus and other possible serious side effects? These are the reasons this drug was not prescribed to my husband.

    • Tiffany says:

      I am 33, dx PPMS in 2013. (“Super rare” for my young age, I quote because I don’t feel it’s as rare as I feel misdiagnosed or overlooked) I just had my 4th infusion (2 half, 2 full doses) I went from 4 new lesions and increase in size of 3 down to 1 new lesion on my last 2 scans. Although it seems slow the lesions, my physical progression has not slowed. I also begin to have a severe increase in general and back pain as well as fatigue 3-4 months post infusion. The 2 months leading up to my next one feel almost torturous. I don’t know what my prognosis is for other side effects by I’m stuck between a rock and a hard place with no other options.

  8. Tom says:

    37yr male. First round of Ocrevus infusions in Feb. 2019. Dx with RRMS in Oct. 2018, but I suspected MS for at least seven years. Same story as many of us, no one believed my symptoms until I ended up in the hospital due to a bad flair up. Brain MRI in Jan. 2019 and then again in April 2019, both show new lesions. Progression continues. Doctors hopeful I will stabilize soon. Based on all the the research, aggressive and early treatment seems to be the best decision. However, I also have lesions in my cervical spine, so maybe my journey with this disease will not be altered by these drugs. Have access to some of the best doctors, but I guess there is not much they can do. Recently, I stopped being mad at the reactive treatment approach of the MS medical society and started fighting my life long battle with this disease on my terms. Going to continue with Ovrevus for at least two more rounds of infusions. Stay strong, resilient, well informed, and positive. That’s all any of us can really do.

  9. Scott Bredeson says:

    I will never use Ocverus again. One of the side effects is upper respiratory tract infections. I got pneumonia and also I am still dealing with severe wheezing in my upper chest. I will be looking for other alternatives.

  10. Shannan Hannula says:

    I was diagnosed with RRMS in 2002 and after 5 years on BetaSeron self-injections with 11 new lesions detected by MRI I was changed to Tysabri infusions. I have had NO new lesions or exacerbations but after 12 years on Tysabri due to the high risk of PML my doctor wants me to switch from Tysabri to Ocrevus. None of the information I have read compares Ocrevus results to Tysabri results, and I see to PML warning on Ocrevus too so I am hesitant to switch. I really appreciate reading comments from Ocrevus patients who have posted on this site!

  11. Larry Cahill says:

    Everyone gets 600 mg infusion every six months no matter what their weight is. What is the best weight a person should be for the 600 ml give you the best result?
    Wouldn’t it be better to make the dose based on a persons weight? Not one size for all.
    “Exposure to the therapy was 26% higher in patients with relapsing MS under 60 kilograms (kg), and 21% lower in those above 90 kg of body weight versus a 75 kg reference patient.”

  12. Iman Farag says:

    I am 60 diagnosed MSPP in 2010. Is the effectiveness of Ocrevus affected by patients age and or MS duration? Is symptoms treatement more reliable due to time considerations.?

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