The MouseDoc and I want to have a little bit of fun in anticipation of the late-breakers at ECTRIMS and at the same time do a thought experiment.
We want to see how wise the crowd is when it comes to predicting trial results.
Aware crowds may be wiser than individuals. In the book ‘The Wisdom of Crowds: Why the Many Are Smarter Than the Few and How Collective Wisdom Shapes Business, Economies, Societies and Nations’ James Surowiecki argues that the aggregation of information in groups, results in decisions that are often better than could have been made by any single member of the group. He opens the book with an anecdote about Francis Galton’s surprise that the crowd at a county fair accurately guessed the weight of an ox when their individual guesses were averaged (the average was closer to the ox’s true butchered weight than the estimates of most crowd members).
We want to see how wise you are when it comes to guessing the outcome of the two phase 3 trials programmes being presented at ECTRIMS. We know they are positive, but how positive is the question? To make it a competition we will be giving away two prizes; a lego MRI scanner set or one of our #ThinkSocial Bart-MS T-shirts. You can choose your prize.
Study 1: Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis (OPTIMUM)
Please note the Janssen Pharmaceutical Company announced positive top-line results stating the study met its primary and most secondary endpoints. As you know ponesimod is a second-generationn S1P modulator. The question is how good will it be compared to Teriflunomide? It may help to remind you that fingolimod, the first licensed S1P modulator, reduced the annualised relapse rate by 52% compared to interferon-beta-1a (Avonex) in the TRANSFORMS study, but had no significant effect on disability progression.
Study 2: Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis (ASCLEPIOS I & II)
Novartis has announced that both of their phase 3 trials of ofatumumab vs. teriflunomide met their primary outcome. In ASCLEPIOS I and II, ofatumumab (OMB157) met primary endpoints to reduce the annualized relapse rate over Aubagio (teriflunomide) in patients with relapsing forms of MS (RMS) and that key secondary endpoints of delaying time to confirmed disability progression were also met.
Ofatumumab is a 3rd-generation anti-CD20 monoclonal antibody. Ocrelizumab is already licensed and was compared to interferon-beta-1a (Rebif) in two parallel phase 3 trials (OPERA I & II); ocrelizumab reduced the annualised relapse rate by 47% and the rate of 3-month confirmed disability progression by 40% compared to interferon-beta in these trials.
I have recently argued that ofatumumab may be underdosed and that as a result, it won’t do as well against teriflunomide (which has similar efficacy to Rebif), compared to what ocrelizumab did against Rebif. Do you agree with me or not?
So please complete the survey below and leave your email address and name if you want to enter the draw for the prize.
CoI: multiple
MD Here….I asked a question in the comments
Ahhhhh…. This is the best crowd sourced fun yet!
You know us we always like abit of fun. Posanimod has a similar mechanism of action to fingolimod siponimod, ozanimod etc
Ofatumumab has a similar mechanism of action to rituximab, ocrelizumab but is a monthly injection under the skin rather than an infusion.
Lastly now I now what the kids of the people at Queen Square and Nottingham get for Christmas:-)
Wonder about a Lego mouse
Nice idea but sadly the majority are always wrong, otherwise we would all make millions on the stock markets. It’s just human nature, which is also the reason communism has failed because it goes against human nature, this in turn fuels change like a pendulum swinging backwards towards the more extreme end of the pendulum we reach the more powerful the change will be. Humans never change, perhaps it needs another evolutionary step to change our thinking.
It is the mean of the crowd that counts, not the individual.
I think you are better with this one:
Extraordinary Popular Delusions and the Madness of Crowds
Charles Mackay
It’s so annoying that these new drugs are compared to Rebif, rather than against one of the newer medications, and sheesh- 3 month window? Too short by half.
Can’t guess because a. I live in Canada and b. Have lost my mind due to MS and struggle with reading studies. But as with many who think they know about MS when they just understand the minimum, i’ll Try anyway!
The two new DMTs are being compared to teriflunomide and not Rebif.
If the crowd was wiser, we wouldn’t have Trump or Boris in top dog positions. And we wouldn’t be leaving the EU.
Don’t worry, we won’t be leaving the EU 😉
😀
That´s what I was thinking. Though, Trump lost the popular vote.
I am a neurologist, so I will not compete for the prizes. My guess in both trials is that ponesimod and ofatumumab will best Aubagio on ARR by only 30% and disability by only 20%.
This would male ofatumumab look poor.
I predict Ofatumumab will ~38% on ARR and ~25% on CDP and Ponesimod 21% on ARR and 9% on CDP.
In phase 2 it surpressed new lesions by 100% beating Ocrelizumab. I suspect it will do better then Ocrelizumab. But will be worse then Alemtuzumab in brain atrophy. Posenimod in conjunction with tecfidera stopped ms completely. I suspect as good as fingo but safer. Ozanimod will beat all 2 hands down. Again targets different sp1 and sp2.
But Novartis has dialled down the dose to allow B-cell reconstitution to occur very quickly. Also, relapses and MRI are not the disease, it is disability progression that is more important. Ocrelizumab data shows that latter.
Being a fan of Daniel Kahneman, you have done something that will bias the crowd – you’ve provided a anchor and that can lead to anchoring bias 🙂
OK, where do I get a Lego MRI set?
When you look at the cost if is about the same as an MRI scan
http://shop-mri.amazings.eu/MRI-small-7sets.html
Wow
We bought a box full, but the conditions of the purchase were that we can’t resell them.
Here is my prediction that will never happen::
1. Ponesimod would not outperform fingolimod head to head.
2. Ofatumumab would not outperform rituximab or rituximab’s humanized clone (ocrezulimab) head to head.
3. Both of these drugs would never outperform alemtuzumab and HSCT.
4. None of the above drugs will have an effect on innate immunity therefore very little if any effect on stopping MS progression.
The madness and greed goes on and on. Teriflunomide is the next generation low lying fruit comparison drug, almost like a second generation CRAB drug
It is time for neurology to take a stand at these conferences on behalf of their patients and start asking the relevant questions that further MS research, not stagnate it.
I agree. We are entering an era of the me-toos. What we need is novelty. New treatments targeting new and interesting mechanisms; testing hypotheses rather than positioning themselves for a marketing war.
Agreed. Well stated.
Wasn’t Biogen ant lingo trial reporting 2nd phase results?
I love the Lego mouse! Who made it? Brilliant!
I dont know I found the picture on the internet
There is quite a bit about lego MRI sets on the web and how they are helping children understand what to expect in the MRI scanner, at various NHS hospitals. A very good idea.
https://www.esneft.nhs.uk/ipswich-dad-builds-lego-hospital-scanner/
Just got diagnosed after more than 20 years of having the disease, about to start treatment with teriflunomide.
Sad to see that even though it seems that a lot has been going one during the past 10 years… We are still well under the EAE spell. T cells, B cells, T cells again, B cells again, let’s get rid of both, but innate immunity but it’s virus and now, of course, the microbiome. We get metoos and monoclonals with sides born from the internist son of Stephen King and a psycho hematologist but no multitarget treatments and no reasonable remission inducing scheme for all the newly diagnosed. Aggressive focus in prehab while EDSS is low? Do you mean keep your job, take up pilates and save for disability while you still can?
So… Whomeverimod will never be tested head to head to fingolimod, the new antiCD20 kid on the block won’t be tested against rituxi and the newly diagnosed 20 somethings will keep being worried about buying gluten & dairy free NON GMO magical ketones instead of getting as strong as they can while they can.
The trials we want are not the trials that get done, sucks as a doctor and as a patient.
Will follow ECTRIMS19 between heavy squat sets by the swimming pool in order to keep my n=1 going, while I still can.
Too angry to play the game now, LOL. But thanks for the blog.
That is a comment that I have a great deal of agreement with.
Thanks Angela. An older MSer after an extraordinarily fortunate life ( a geek in science, engineering, economics, law, in a loving family etc ) and now a confused imposter on whomeverimod, I am still fortunate but vacant, spending my time in exercise, sleep, trying to sing in a choir, and wondering what I did yesterday and if I’ve taken my meds. Perhaps I should be angry too.