Vidofludimus - a Slam Dunk, or not?
Many will say there is no place for teriflunomide me-too in the MS therapeutic landscape. Do you agree?
Another positive result and new treatment for people with MS, in particular those with primary progressive MS.
Today's press release shows that vidofludimus, an inhibitor of dihydroorotate dehydrogenase (DHODH), reduced 24-week confirmed disability worsening (CDW) by 20% compared to placebo and 30% in subjects with primary progressive MS (PPMS)> Please note these are relative risk reductions we will need to see the results for the absolute reduction and the number needed to treat to prevent one CDW. Significantly, in the subpopulation without Gd-enhancing lesions at baseline, 24-week CDW was reduced by 29% compared to placebo. The impact of vidofludimus on the annualised rate of per cent brain volume change was relatively modest, i.e. 5% better than placebo. However, it did impact thalamic volume, i.e. it reduced some end-organ damage. Annualised thalamic volume loss was reduced by 20% in the vidofludimus group compared to placebo. The total volume of new or enlarging T2 lesions showed a substantial difference between vidofludimus calcium and placebo over time, with vidofludimus calcium decreasing and placebo increasing the volumes; the mean per cent change was -0.22% for vidofludimus and +2.97% for placebo at month 24. Importantly, no new safety signals were identified with vidofludimus.
Vidofludimus has a similar mode of action to teriflunomide. As these results are relatively modest compared to other high-efficacy DMTs and tolebrutinib, the first BTK inhibitor to report out in non-relapsing MS, many will say there is no place for teriflunomide me-too in the MS therapeutic landscape. I disagree.
Firstly, vidofludimus has fewer off-target effects than teriflunomide, i.e. it is better tolerated with less liver toxicity. It also has at least two other modes of action. It has been shown to activate Nurr1, which may be neuroprotective. Whether vidofludimus gets into the central nervous system to activate Nurr1 is a moot point and needs further work. The third mode of action is its antiviral effects, particularly its impact on EBV (see abstract link below).
Vidofludimus is high on my list of anti-EBV antiviral agents to treat MS. We now need to show that it works via an EBV mechanism. I sincerely hope Immunic, the company developing the drug, will invest in finding this out. I have many ideas on how to look at EBV biology in vidofludimus-treated pwMS.
Vidofludimus is one of the agents on my list of maintenance therapies after an induction therapy. It would now be my go-to agent for testing in the iTeri study, which would have to be now called the iVido study.
Do you find these results exciting? Or is there no place for a teriflunomide me-too in the MS therapeutic landscape? Would you participate in the iVido study?
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Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
“reduced 24-week confirmed disability worsening (CDW) by 20% compared to placebo and 30% in subjects with primary progressive MS (PPMS)”
How can an MSer interpret this? It’s the equivalent of mobile phone deals which say that for £xx a month you get 80GB of data! It doesn’t mean anything.
If this therapy is reducing disability worsening by 20%, what’s driving the disability worsening ie the mechanisms / drivers not impacted by this therapy.
Surely MSers want therapies that stop disability worsening, or at least slow it down to a level that has minimal impact during their lifetime. Are we likely to see such therapies in the not too distant future ie therapies which reduce disability worsening by 75%, 90%? Vidofludimus results appear very underwhelming.
Yes, I would gladly do the study- but I’m 67, in the US, and they would never take me in the study. Sigh. I think Terifl does help me, as I could stagger a little farther on my daily walk when I take it (and saw a decrease when I was not taking it), but doctors don’t believe patients. Just what the sales reps tell them, unfortunately.