“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.
Even if it's "just" a safer teriflumonide, that seems like a good thing.
I've done the induction therapy. I'd at least consider a study, though since I'm in the US I'd have to consider whether I think it would actually be funded.
I’d try it in a New York minute. Perhaps this is something that is safe for us old p/w MS. Anything that would help. Just my thought. Thanks for this, Prof G. I note all the differing opinions, but I believe that’s a good thing. (Yours truly “treat MS like cancer..) :)
There are actually quite a few things that should be available, or at least trialing (if you are able to enter the trial) by end of the year. And a few reparative therapies/strategies in the next few years. I know it's kind of crass to say "just hang on," but seriously... there actually is something to be optimistic about nowadays for the near future.
I asked to be switched to teri, mainly for its anti-EBV properties as I have had a few EBV-reactivations. I was on interferons and DMF before that. Vidofludimus has been on my list. I think I'd like to wait for some more results. At the moment, the side-effects of teri are manageable, so there's no rush to switch.
I do wonder what 15 years of teri will do to my liver. After 2 years of teri, ALT, AST are always on the high side (just outside normal range), and I've developed a high cholesterol/dyslipedemia. Is your the guess that longterm use of vidofludimus would be less problematic for liver and dyslipedemia?
I would absolutely use this. Right now. Wish it were ready to go. I’ve done Mavenclad - activity. Kesimpta for two years and looking at stopping. This would be the perfect deescalation. Comorbid reactivating EBV continues to kick up MS here.
That isn't what the trial results showed! They showed a 20% relative risk reduction, which is VASTLY different than what you have written in this article!
"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..."
a) "Immunic Announces Vidofludiumus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial"
b) "-Reduced Relative Risk of 24-Week Confirmed Disability Worsening Events by 20% in Overall Study Population Compared to Placebo..."
c) "...Reduced Relative Risk of 24-Week Confirmed Disability Worsening Events in Patients Without Gadolinium-Enhancing Lesions..."
d) "In the overall PMS patient population...vidofludiumus calcium reduced the relative risk of 24-week confirmed disability worsening...by 20% compared to placebo"
e) "...vidofludimus calcium was associated with a 30% reduction in the relative risk of 24wCDW events in the primary progressive multiple sclerosis...study population...compared to placebo"
f) "Vidofludiumus calcium reduced the relative risk of 24wCDW events in patients without gadolinium-enhancing lesions at baseline by 29% compared to placebo"
This Immunic Press Release is also grossly misleading and misrepresentative when it says parts such as the following:
a) "The tremendous reduction of confirmed disability worsening in PMS patients..."
-A 20% relative risk reduction (again, it seems safe to assume that the absolute risk reduction is very, very small and thus the NNT will be high) for 24-Week CDP is HARDLY "a tremendous reduction"
b) "We are particularly thrilled to see such a clinically meaningful effect in the PPMS population, with a 30% reduction in the relative risk of 24-week confirmed disability worsening events..."
-again, a 30% relative risk reduction (again, it seems safe to assume that the absolute risk reduction is very, very small and thus the NNT will be high) for 24-Week CDP is HARDLY a "thrilling...clinically meaningful effect"
The results math is only one tool in the complete picture. Shouldn't get too hung up on just the "numbers needed to treat." It's almost like only reading the abstract and leaving the rest on the table.
I disagree. I think NNT is extremely relevant and important for patients to be aware of, as not all patients will receive the treatment benefit, but many patients don't understand this aspect.
I'm really not trying to be argumentative or rude. But we should be aware of everything in sum total. No, not all recipients will receive a benefit... but what should they get instead? A "numbers needed to treat" is one part of the picture, but not the most important part. The miracle… sorry, MEDICAL establishment is still far away providing a highly effective disease modifying medication that is equally effective for everyone. In the meantime people need help and they need hope. A "clinically meaningful effect" is better than nothing, which is pretty close to what there is now for progressive disease.
Also, regarding the term "high efficacy DMT": There is no standard definition or criteria was to what constitutes a "high efficacy DMT" in the USA as far as I am aware. In the UK, the Association of British Neurologists has established the criteria as a DMT that reduces relapses by 50% or more. However, research (which I am happy to provide upon request) has proven that relapses and RAW (relapse-associated worsening) barely contribute to progression in MS-rather, almost all progression in MS is due to PIRA. So what is the point of "high efficacy DMTs" that reduce relapses by 50% or more? Okay, people don't have to suffer the symptoms of a relapse, but reducing relapse doesn't prevent progression.
Also, while on the topic of treatments for progressive MS that have a "clinically meaningful effect," are you aware that the FDA's approval documentation for Ocrevus for PPMS found the following: treatment benefit was seen in less than 5% of trial participants (ORATORIO/WA25046 clinical trial, the only trial the FDA relied on for their controversial and divided approval decision); no treatment benefit was seen in women; treatment effect disappeared after Week 18; and there was no statistically significant difference for the endpoint of 3 month CDP between Ocrevus and placebo if imputed data wasn't used (and imputed data wasn't used in the Ocrevus for RMS trials, OPERA I and II). Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761053orig1s000medr.pdf.
Do you feel that Ocrevus for PPMS, then, constitutes a treatment for progressive MS that has a "clinically meaningful effect"?
I'm not trying to be rude or argumentative either, and I agree that those with progressive MS need both help and hope. However, my concern is that grandiose language such as "The tremendous reduction of confirmed disability worsening"; "such a clinically meaningful effect in the PPMS population"; and "vidofludiumus calcium may represent a novel and exciting approach...," as examples.
My issue is that this Press Release and article, along with other information (such as the results of ORATORIO trial of Ocrevus for PPMS) contains intentionally misleading and misrepresentative information that distorts and exaggerates the true findings of the results of the CALLPER study. This information lacks transparency.
The ultimate question is if a treatment that offers a treatment benefit of a relative risk reduction of 20% or 30% for 24 Week CDP with a low absolute risk reduction and a high NNT constitutes a "clinically meaningful effect." I would argue that it most definitely does not.
The information in your post is still wrong per my review of the Immunic Press Release. Nowhere does this Press Release state that vidofludimus calcium "...reduced 24-week confirmed disability worsening (CDW) by 20% compared to placebo...".
Rather, the Press Release states: "In the overall PMS patient population (n=467), vidofludiumus calcium reduced the relative risk of 24-week confirmed disability worsening (24wCDW) events based on changes in the expanded disability status scale (EDSS) by 20% compared to placebo."
Yes, the Press Release is distorted, misleading, confusing, and contradictory. They are trying to exaggerate and "hype up" the results of the CALLIPER trial, likely as they try to get FDA approval for vidofludiumus calcium.
Also have secondary progressive and I’m not on the DMT. Tested positive for EBV but my doctor won’t tell me if it’s a reactivation or an old virus. Will follow with great interest.
I'd be interested to know more and maybe participate in tests but if I'm going to come off Ocrevus it's not going to be for a placebo so I guess thats still going to be a long way off.
“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.
I agree on both counts. Difficult to relate and underwhelming. This is why we need to use vidofludimus after an induction therapy.
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.
Same here in states…you took it? I wonder if I could tolerate it..
I have PPMS and would gladly join a trial. However, as so often before, I suspect that, at 73, I will be told I’m too old!!
Maybe us older MSers could be very useful. If we’re prepared to take part in the trials.
Can’t take part in a trial, but I’d try it!!
Even if it's "just" a safer teriflumonide, that seems like a good thing.
I've done the induction therapy. I'd at least consider a study, though since I'm in the US I'd have to consider whether I think it would actually be funded.
I’d try it in a New York minute. Perhaps this is something that is safe for us old p/w MS. Anything that would help. Just my thought. Thanks for this, Prof G. I note all the differing opinions, but I believe that’s a good thing. (Yours truly “treat MS like cancer..) :)
There are actually quite a few things that should be available, or at least trialing (if you are able to enter the trial) by end of the year. And a few reparative therapies/strategies in the next few years. I know it's kind of crass to say "just hang on," but seriously... there actually is something to be optimistic about nowadays for the near future.
Hi Christopher, I hope so..
:oD
I asked to be switched to teri, mainly for its anti-EBV properties as I have had a few EBV-reactivations. I was on interferons and DMF before that. Vidofludimus has been on my list. I think I'd like to wait for some more results. At the moment, the side-effects of teri are manageable, so there's no rush to switch.
I do wonder what 15 years of teri will do to my liver. After 2 years of teri, ALT, AST are always on the high side (just outside normal range), and I've developed a high cholesterol/dyslipedemia. Is your the guess that longterm use of vidofludimus would be less problematic for liver and dyslipedemia?
I’d definitely take part in the study. When I apply for studies I don’t get responses so I no longer apply.
New info -for me - unexpectedly positive. As of now, it's unavailable where I am. But I will be staying alert....
Teriflumide didn't work for me, 3 relapses in 14 months. I wouldn't recommend to anyone.
I would absolutely use this. Right now. Wish it were ready to go. I’ve done Mavenclad - activity. Kesimpta for two years and looking at stopping. This would be the perfect deescalation. Comorbid reactivating EBV continues to kick up MS here.
That isn't what the trial results showed! They showed a 20% relative risk reduction, which is VASTLY different than what you have written in this article!
"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..."
ALSO Per the Immunic Therapeutics Press Release:
a) "Immunic Announces Vidofludiumus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial"
b) "-Reduced Relative Risk of 24-Week Confirmed Disability Worsening Events by 20% in Overall Study Population Compared to Placebo..."
c) "...Reduced Relative Risk of 24-Week Confirmed Disability Worsening Events in Patients Without Gadolinium-Enhancing Lesions..."
d) "In the overall PMS patient population...vidofludiumus calcium reduced the relative risk of 24-week confirmed disability worsening...by 20% compared to placebo"
e) "...vidofludimus calcium was associated with a 30% reduction in the relative risk of 24wCDW events in the primary progressive multiple sclerosis...study population...compared to placebo"
f) "Vidofludiumus calcium reduced the relative risk of 24wCDW events in patients without gadolinium-enhancing lesions at baseline by 29% compared to placebo"
This Immunic Press Release is also grossly misleading and misrepresentative when it says parts such as the following:
a) "The tremendous reduction of confirmed disability worsening in PMS patients..."
-A 20% relative risk reduction (again, it seems safe to assume that the absolute risk reduction is very, very small and thus the NNT will be high) for 24-Week CDP is HARDLY "a tremendous reduction"
b) "We are particularly thrilled to see such a clinically meaningful effect in the PPMS population, with a 30% reduction in the relative risk of 24-week confirmed disability worsening events..."
-again, a 30% relative risk reduction (again, it seems safe to assume that the absolute risk reduction is very, very small and thus the NNT will be high) for 24-Week CDP is HARDLY a "thrilling...clinically meaningful effect"
c
The results math is only one tool in the complete picture. Shouldn't get too hung up on just the "numbers needed to treat." It's almost like only reading the abstract and leaving the rest on the table.
I disagree. I think NNT is extremely relevant and important for patients to be aware of, as not all patients will receive the treatment benefit, but many patients don't understand this aspect.
I'm really not trying to be argumentative or rude. But we should be aware of everything in sum total. No, not all recipients will receive a benefit... but what should they get instead? A "numbers needed to treat" is one part of the picture, but not the most important part. The miracle… sorry, MEDICAL establishment is still far away providing a highly effective disease modifying medication that is equally effective for everyone. In the meantime people need help and they need hope. A "clinically meaningful effect" is better than nothing, which is pretty close to what there is now for progressive disease.
Also, regarding the term "high efficacy DMT": There is no standard definition or criteria was to what constitutes a "high efficacy DMT" in the USA as far as I am aware. In the UK, the Association of British Neurologists has established the criteria as a DMT that reduces relapses by 50% or more. However, research (which I am happy to provide upon request) has proven that relapses and RAW (relapse-associated worsening) barely contribute to progression in MS-rather, almost all progression in MS is due to PIRA. So what is the point of "high efficacy DMTs" that reduce relapses by 50% or more? Okay, people don't have to suffer the symptoms of a relapse, but reducing relapse doesn't prevent progression.
Also, while on the topic of treatments for progressive MS that have a "clinically meaningful effect," are you aware that the FDA's approval documentation for Ocrevus for PPMS found the following: treatment benefit was seen in less than 5% of trial participants (ORATORIO/WA25046 clinical trial, the only trial the FDA relied on for their controversial and divided approval decision); no treatment benefit was seen in women; treatment effect disappeared after Week 18; and there was no statistically significant difference for the endpoint of 3 month CDP between Ocrevus and placebo if imputed data wasn't used (and imputed data wasn't used in the Ocrevus for RMS trials, OPERA I and II). Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761053orig1s000medr.pdf.
Do you feel that Ocrevus for PPMS, then, constitutes a treatment for progressive MS that has a "clinically meaningful effect"?
I'm not trying to be rude or argumentative either, and I agree that those with progressive MS need both help and hope. However, my concern is that grandiose language such as "The tremendous reduction of confirmed disability worsening"; "such a clinically meaningful effect in the PPMS population"; and "vidofludiumus calcium may represent a novel and exciting approach...," as examples.
My issue is that this Press Release and article, along with other information (such as the results of ORATORIO trial of Ocrevus for PPMS) contains intentionally misleading and misrepresentative information that distorts and exaggerates the true findings of the results of the CALLPER study. This information lacks transparency.
The ultimate question is if a treatment that offers a treatment benefit of a relative risk reduction of 20% or 30% for 24 Week CDP with a low absolute risk reduction and a high NNT constitutes a "clinically meaningful effect." I would argue that it most definitely does not.
The information in your post is still wrong per my review of the Immunic Press Release. Nowhere does this Press Release state that vidofludimus calcium "...reduced 24-week confirmed disability worsening (CDW) by 20% compared to placebo...".
Rather, the Press Release states: "In the overall PMS patient population (n=467), vidofludiumus calcium reduced the relative risk of 24-week confirmed disability worsening (24wCDW) events based on changes in the expanded disability status scale (EDSS) by 20% compared to placebo."
These are 2 VERY and FAR different things!
Actually it says it right at the top of the press release on the website, in the bullet points.
Yes, the Press Release is distorted, misleading, confusing, and contradictory. They are trying to exaggerate and "hype up" the results of the CALLIPER trial, likely as they try to get FDA approval for vidofludiumus calcium.
"one of the agents on my list of maintenance therapies after an induction therapy"
Has anyone tested this type of DMT along with an anti-CD20? Are such studies planned?
You have said often that people on anti-CD20 eventually start to deteriorate clinically.
The deterioration increases if the anti-CD20 is stopped or replaced by something less effective (that's my observation, n=1).
We need something on top of the anti-CD20, preferably something off-patent and affordable
Teriflunomide
How can I get on a trial for it? Can anyone please advice? I have PPMS
I would try it, I have Secondary Progressive & am not on any DMT.
Also have secondary progressive and I’m not on the DMT. Tested positive for EBV but my doctor won’t tell me if it’s a reactivation or an old virus. Will follow with great interest.
Is this something that would be used along side a high efficacy DMT? Like used along with ocrevus?
After ocrelizumab. The iVido study.
I'd be interested to know more and maybe participate in tests but if I'm going to come off Ocrevus it's not going to be for a placebo so I guess thats still going to be a long way off.