Genius

G

My #ECTRIMS2019 highlight #3 is the elevation of fatigue to be the first secondary outcome measure in a clinical trial. Was this genius or a marketing coup? I would have loved to be a fly on the wall when the steering committee of the OPTIMUM study made the decision to bump fatigue to the top of the secondary outcomes.

If you have MS you know that the most troubling symptom the majority of MSers complain about is fatigue. Therefore for a DMT to be able to claim it reduces fatigue is a big deal. I suspect MSers will find the promise of fatigue reduction a very compelling reason to choose one DMT over another.

The Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis (OPTIMUM) study was positive. Compared to teriflunomide ponesimod reduced the relative annualised relapse rate (ARR) by 30.5% (P<0.0003) and 3-month CDP (confirmed disability progression) by 17% (not significant).

If you recall this study was one of the studies we asked the Crowd to predict the results of. In fact, they were almost spot-on; they predicted that ponesimod would reduce the ARR and CDP compared to teriflunomide by 33.8% (interquartile range=24.5-44.3%) and 21.2% (interquartile range=10.0-25.0%), respectively. My interpretation is that the Crowd did very well; well done!

Please note that I will be contacting the winners of the #ECTRIMS competition very soon. There will two awards one for the OPTIMUM study and a second award for the ASCLEPIOS I & II studies.

When it comes to the S1P wars ponesimod is setting itself up very nicely to go head-2-head with newer entrants, i.e. siponimod and ozanimod. In my opinion, the safety profile of ponesimod is reasonably good, the lack of need for 1st-dose monitoring will put it alongside ozanimod in the S1P Me-Too wars. The question everyone is now asking ‘Will fatigue be the trump card?’. What do you think?

CoI: multiple

About the author

Prof G

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

7 comments

    • RRMS – low hanging fruit; easy to get a positive trial

      SPMS – harder to get a positive trial and surely Novartis does not want siponimod to cannibalise fingolimod’s market? You need to ask Novartis. Importantly, the FDA has not licensed siponimod for SPMS, but relapsing forms of MS, which includes active SPMS. Let’s wait and see what the EMA has to say about non-relapsing SPMS (inactive SPMS in the FDA’s books).

  • It might be a marketing coup, but I am sure it will push other DMT studies to include fatigue as an important outcome measure. Regardless of the reason, this is a huge win for MS-patients.

  • What kind of fatigue? Fatigue to me is an umbrella term for very different things. There’s what I think of as a systematic fatigue, a washed out feeling. Then just the fatigue of tired nerves, resulting in more difficulty walking etc. Fatigue as a term is very vague.

    • Anon, yes you’re so right to ask what kind of fatigue. I feel the same. There’s a tiredness that can be overcome by a short rest. An overwhelming exhaustion that will not disappear after a nap. A fatigue that can be overcome by aerobic exercise. Drowsiness caused by medication and muscle fatigue that will not allow you to move your legs at all. If a Pharma company wants to claim a medication will work for fatigue, I would want to know which one.

  • “Compared to teriflunomide ponesimod reduced the relative annualised relapse rate (ARR) by 30.5% (P<0.0003) and 3-month CDP (confirmed disability progression) by 17% (not significant).“ – So who cares? It does no better in slowing disability progression than teri. Basically, you just have less fatigue while your brain is being destroyed.

  • Is this not a triumph of the relative over the absolute? Ponesimod doesn’t appear to have made fatigue (by whatever definition) any better, it just didn’t make it worse, unlike teriflunomide. It’s a good thing that your medication doesn’t make you feel worse, but to claim that ponesimod makes your fatigue better would be going way too far, surely.

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