Multiple Sclerosis Research Repository

March 31, 2025

In Re: Dr. Amit Bar-Or being awarded the 2025 John Dystel award due to your nomination

Dear Dr. Hafler,

I am writing this feedback in response to the awarding of the John Dystel award to Dr. Amit Bar-Or (press release: https://www.eurekalert.org/news-releases/1077660).

In the above-cited press release, you are quoted as saying that Dr. Bar-Or’s “involvement in clinical trial programs and translation work has led to B-cell therapies that have been transformative in the treatment of MS.”

I would like to provide you with my feedback as someone who has a loved one with MS that very much disagrees with your above-quoted assertion, which is as follows:

1. Dr. Bar-Or was one of the ORATORIO Clinical Investigators.  I have reviewed the ORATORIO clinical trial documentation as well as the FDA approval document of Ocrevus for PPMS and was sufficiently disturbed and alarmed by my findings that I submitted a Citizen Petition to the FDA last month requesting that they withdraw their approval of Ocrevus for PPMS because this approval appears to have violated the statutory regulations, as the evidence from the ORATORIO clinical trial did not meet the statutory regulatory standard of “substantial evidence of effectiveness,” as the single clinical trial (ORATORIO) which served as the sole evidence/basis for the FDA’s approval of Ocrevus for PPMS was not an “adequate and well-controlled trial.”  Here is the link to this Citizen Petition currently published on the docket at Regulations.gov: https://www.regulations.gov/docket/FDA-2025-P-0547

The FDA approval documentation of Ocrevus for PPMS evidences that the ORATORIO 

trial was riddled with such serious, severe and egregious issues that the clinical reviewer 

team leader, Dr. John Marler, wrote that this trial was not an adequate and 

well-controlled trial. 

2. The evidence of the B-cell therapies (really, lack of evidence) in regards to their evidence of efficacy (really, lack thereof) against progression/confirmed disability worsening/disability accumulation is FAR from “transformative.”  I will again refer to the example of Ocrevus and the results from the OPERA I and II clinical trials for RMS and the ORATORIO trial for PPMS:

1. From the OPERA I and II clinical trials using pooled data from both trials: The Number Needed to Treat would be 18.5, meaning that 18.5 patients would need to be treated with Ocrevus for 1 patient to receive the benefit of a 40% relative risk reduction (or a 5.4% absolute risk reduction) of 12-week confirmed disability progression
2. From the ORATORIO clinical trial for PPMS: The Number Needed to Treat would be 15.6, meaning that 15.6 patients would need to be treated with Ocrevus for 1 patient to receive the benefit of a 24% relative risk reduction (or a 6.4% absolute risk reduction) of 12-week confirmed disability progression

There is nothing “transformative” about a “therapy” with NNTs that are this high 

and absolute risk reductions that are this low. 

Research shows that relapses and relapse-associated worsening (RAW) barely contribute to progression in MS and that almost all progression is due to PIRA.  Per research, Ocrevus showed little efficacy against PIRA.  Additionally, research shows that there is only a weak to moderate association between lesions and progression in MS.  So while one could make the argument that B-cell MS “therapies” such as Ocrevus are “transformative” because they show greater efficacy against relapses and conventional MRI activity than other MS “DMTs” (I do not use this term because the evidence doesn’t support that any of these “therapies” show efficacy against the underlying pathology of MS-rather, they appear to mitigate certain manifestations of MS such as the relapses and conventional MRI activity which are not the main or even significant drivers of progression), efficacy against relapses and conventional MRI is far from “transformative.”  What would be “transformative” is if these “therapies” showed far more evidence of efficacy against progression/disability accumulation.  

There is much more I could and would like to write about this topic, but for now, I will stop here.  When time permits, I will send the rest of the thoughts and information that I would like to send.  In closing, I find the misrepresentation of the MS DMTs very disturbing on many levels, including ethically, which is why I will speak out against them as much as I am able to.  

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