Monday, 28 August 2017

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

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


  1. 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.

  2. 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..

    1. 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

  3. This is disappointing, I had hoped for better numbers from this one. Been watching this for a long time.

  4. 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.


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