#NewsSpeak: Results from CHANGE-MS Phase 2b Study

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Are HERVs in the final common pathway that leads to demyelination in MS? #NewsSpeak #ResearchSpeak


It is very difficult for me to comment on these results without seeing the data firsthand. However, as there is no difference at 6-months between active- and placebo-treated subjects this trial must be interpreted as being negative. Please note that GNbAC1 targets the envelope protein of probably one human endogenous retrovirus or HERV.  GNbAC1 is a monoclonal antibody and is not an antiviral agent, hence this study does not exclude a role of HERVs in the pathogenesis or molecular pathway of MS. 

Press release: BusinessWire. GeNeuro and Servier Announce Six-Month Results from CHANGE-MS Phase 2b Study in Multiple Sclerosis. August 28, 2017 01:30 AM Eastern Daylight Time


GeNeuro and Servier announced their 6-month results from the 12-month CHANGE-MS Phase 2b study of three doses of GNbAC1 for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The data showed that GNbAC1 is well tolerated and that there is no statistical difference at 6-months between GNbAC1 and placebo in the study’s primary endpoint of reducing the number of cerebral Gad-enhancing lesions as measured by MRI, nor on the other MRI measures of neuroinflammation. Relapses in the overall population decreased by over 50% relative to the year prior to study but there was no significant difference at 6 months between treated and placebo groups. Based on the unique mechanism of action and pharmacokinetics of GNbAC1, the study will continue, as planned, exploring potential benefits of the drug on MRI and clinical measures, including remyelination properties, with final results from the full 12-month expected in the first quarter of 2018.

GNbAC1 is the result of more than 25 years of research into human endogenous retroviruses (HERVs), including 15 years at Institut Mérieux and INSERM, a French national medical research institute. Found in the human genome, certain HERVs have been linked to various autoimmune and neurodegenerative diseases. Researchers have demonstrated that the retroviral envelope protein encoded by a HERV-W family human endogenous retrovirus (pHERV-W), which has been identified in brain lesions of patients with MS, particularly in active lesions, stimulated inflammatory processes through an interaction with the TLR4 receptor of innate immunity and inhibited neuron remyelination. pHERV-W env has also been identified in the pancreas of Type 1 diabetes (T1D) patients. By neutralizing pHERV-W env, GNbAC1 could at the same time block these pathological inflammatory processes and restore remyelination in MS patients and maintain insulin production in T1D patients. As pHERV-W env has no known physiological function, GNbAC1 is expected to have a good safety profile, without directly affecting the patient’s immune system, as observed in all clinical trials to date.

CoI: multiple

About the author

Gavin

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

9 comments

Leave a Reply to luis fernando Cancel reply

  • Well, despite the fact that this doesn't completely discount endogenous retroviruses as playing a key role in MS etiology, these results are very disappointing. When they expanded the trial to type I diabetes patients, I expected that they were seeing positive results with their MS cohort.

    On a somewhat tangential subject, do you have any thoughts on the BCG vaccine, which has been tried on MS in the past and is now undergoing trials on type I diabetes patients in Boston. Apparently they are using a protocol involving multiple injections over a relatively short period of time. The vaccine seems to work on the genetic level, down regulating some of the genes that are implicated in autoimmune diseases.

  • Using an antibody to target something inside a brain cell, is going to mean an uphill task.The antibody won't get into the brain and probably not in the cell..

    • You right

      Saw an Mit presentation (koch institute) about drug imaging in GBM ,in mouse studies and the drug is all over the place and guess what ?

      Not on the tumor
      One thing that i learn is that the BBB is not at all equal(at least in mouses) there are parts that are more premeable than others
      Obrigado

  • Be careful.
    These results are not complete.
    There are preliminary results at 6 moths.
    The study continues, it lasts one year.
    Geneuro has immediaely supposed that maybe the process could be longer before to see any positive results.
    They after said they had elements confirming this.
    They are going topresent all the data the 28th f october during ECTRIMS in Paris.
    w have to wait.

  • In October 2018, in the Congress of the European Committee for Treatment and Research on Multiple Sclerosis held in Berlin (ECTRIMS 2018), GeNeuro announced that final analysis of the Phase 2b CHANGE-MS clinical study had produced robust results regarding key markers related to MS progression, and that the effects were greater in patients who did not experience inflammatory activity during the study. These patients represent a group of MS patients who are not well served by currently available therapies. The CHANGE-MS results suggest temelimab has the potential to become a totally new mechanism of action targeting a cause of MS progression. Furthermore, they suggest that temelimab could be used as a single agent in patients experiencing progressive MS without active inflammation, or synergistically with existing anti-inflammation MS drugs.

    Source: MS-UK, 28/01/2019

    Is there any more news on temelimab?

    • The company website has news all the time…a paper comes out and its up there.
      Ask how much antibody gets in the CNS that is the answer you want to know.

      However, look at their pipe line. Now this approach is being used in diabetes, peripheral neuropathy, Psoriasis, diabetes and ALS…therefore the MS logic now starts to disintegrates, although many of the above are considered to be autoimmune issues. It starts to sound like snake oil. What next fatigue I suspect (HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
      Lucas S Rodrigues, Luiz H da Silva Nali, Cibele O D Leal, Ester C Sabino, Eliana M Lacerda, Caroline C Kingdon, Luis Nacul, Camila M Romano bioRxiv 693465; doi: https://doi.org/10.1101/693465)

      I am there to be proved wrong. The trial in diabetes should now have finished Q12019. We are now in Q2. Earth shattering results?

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