Nikki J
Moderator
- Joined
- Mar 22, 2012
- Messages
- 17,824
- Reason
- PALS
- Diagnosis
- 04/2014
- Country
- US
- State
- MA
- City
- Boston
I am sharing this comment from facebook with the author’s permission. Keith Mayl is, as he says, an ALS physician and researcher in the UK
I wanted to share some thoughts regarding #NurOwn with the ALS community. I’ve been watching the build up to this day closely and wanted to wait for the FDA Advisory Committee discussion to have access to all the data and evidence before making a comment.
I am an ALS physician-scientist. I have led several clinical trials for ALS including the Tofersen trial, and all the other ASO trials. I strongly advocated for Tofersen and spoke at the Ad Com in support of full approval. I have no conflicts to declare and this opinion is my own.
None of us (physicians/industry) will ever truly know what it means to have ALS, but I sincerely sympathise with the suffering and devastating effects of this disease and I am categorically on your side and will continue to be throughout my career.
I know how much hope and emotion has been invested in the lead up to this day and I know the disappointment is substantial. I want nothing more than to see effective treatments be approved for ALS.
Watching the Ad Com today was difficult, as though 2 different interpretations of the data were being made, with patients and families caught in the middle of it. Hope is not enough to approve a drug and I do believe that the patient voice was not honoured today because of the disparity between the testimonies and the data, which seriously calls into question the messaging that has been communicated to the community about the effectiveness of this drug.
Before even considering effectiveness, I would like to stress that there are serious concerns over the manufacturing quality of this drug. This is truly not acceptable for a drug developer, and calls into question what exactly patients received. This is a disservice to you, make no mistake. The regulatory standards are there to ensure quality, and this point alone is enough to undermine the validity of this drug. I want to stress this because it is unacceptable to have such poor manufacturing processes; you deserve better for giving your lives to participate in the trials and advocating so strongly for its approval. It really pains me to know that a poor quality product has been given to patients. This is not, and never will be acceptable, and this point alone, from a regulatory perspective, is sufficient to deny approval. I am truly disappointed that Brainstorm did not do enough to ensure the quality and manufacturing process of this drug was adequate, because it only serves to harm the data and potentially harm patients.
Second, the absence of preclinical data to support the proposed mechanism of action is another failure and disservice to you. Before a trial even begins, there should be clear and substantial scientific data to support the intended mechanism of action. Without this, it’s like taking a shot in the dark. No convincing arguments were put forward today to support how the drug works. It is not enough to claim that it works by secreting NTFs and immuno modulation, without proving that this is the case and that this approach yields benefit in preclinical models. This is truly disappointing for me to hear as a scientist and as a physician. How can we ever expect the results to be clear when key basic questions remain unanswered? It is not enough to assume a cocktail of NFTs is beneficial, and the minute levels of various NFTs in the CSF following administration, seriously questions how the drug could ever be effective. No data was presented to prove that MCS adhere to the spinal cord and therefore we are unable to know whether they are located in then right place. This is a disservice to you, as there should be no doubts over such fundamental aspects of the drug such as it’s mechanism of action, site of action and persistence in vivo. Without this, how can we ever justify this drug fulfils it’s intended purpose? You deserve better than this and is another major disappointment from Brainstorm.
Next comes efficacy. I hear the testimonies loud and clear, and I do not doubt them. We clearly know very little about this drug and perhaps all the elements aligned in some instances to provide an effect. But the data clearly shows that such an effect is not reproducible, consistent or identifiable within a plausible subset of patients. I do believe that the future of ALS treatment will be far more tailored, and that we are unlikely to end up with a one size fits all approach. This is why we need far better ways of stratifying patients according to their underlying biology, not arbitrary characteristics such as fast or slow, or early or late. Back to the efficacy, the unbiased analysis from the FDA clearly shows negative results from 2 randomised controlled studies on all primary and secondary endpoints. We can debate the adequacy or acceptability of post-hoc analyses, but this must always be taken with caution and such analyses do not make up for otherwise negative pre-specified data.
The data presented is not convincing, and it never was which is why the FDA rejected the BLA on 2 occasions and promoted the Sponsor for more. Instead Brainstorm wasted FOUR YEARS to get us to this day today, instead of hearing the message and doing more to validate this drug. This is a disservice to you. I understand financial constraints may have limited the ability to perform another trial, but that is not a sufficient excuse to persist with negative data and apply statistical methods to look for a signal and exploit patients for years in the process. You deserve better than this. The outcome today was predictable, and the community has been played with for years with hope that something positive might happen today. This is wrong on so many levels and has been difficult for me to reconcile. We must honour your lives, efforts and families every step of the way. We must never exploit your generosity and commitment to research and we must never subject you to bad science or poor quality drugs. There is no credibility if any of that takes place and I am so disappointed that this battle has lingered on for years when your lives and all the resources poured into this program could have been used elsewhere. I fully understand the level of risk ALS patients are willing to take on and I applaud the bravery, but this makes you vulnerable and this should NEVER be exploited. The increased mortality in the treated group is a major concern and was not accounted for in any way. This treatment may have harmed you more than doing good and I cannot accept that.
I care deeply about ALS patients and the community and I hope you can see that. I want to see effective treatments come to life and I am committed to contributing to that as best as I can throughout my career. You truly deserve better than this and we should not applaud Brainstorm. We should be holding them accountable for the inadequacy presented today
I wanted to share some thoughts regarding #NurOwn with the ALS community. I’ve been watching the build up to this day closely and wanted to wait for the FDA Advisory Committee discussion to have access to all the data and evidence before making a comment.
I am an ALS physician-scientist. I have led several clinical trials for ALS including the Tofersen trial, and all the other ASO trials. I strongly advocated for Tofersen and spoke at the Ad Com in support of full approval. I have no conflicts to declare and this opinion is my own.
None of us (physicians/industry) will ever truly know what it means to have ALS, but I sincerely sympathise with the suffering and devastating effects of this disease and I am categorically on your side and will continue to be throughout my career.
I know how much hope and emotion has been invested in the lead up to this day and I know the disappointment is substantial. I want nothing more than to see effective treatments be approved for ALS.
Watching the Ad Com today was difficult, as though 2 different interpretations of the data were being made, with patients and families caught in the middle of it. Hope is not enough to approve a drug and I do believe that the patient voice was not honoured today because of the disparity between the testimonies and the data, which seriously calls into question the messaging that has been communicated to the community about the effectiveness of this drug.
Before even considering effectiveness, I would like to stress that there are serious concerns over the manufacturing quality of this drug. This is truly not acceptable for a drug developer, and calls into question what exactly patients received. This is a disservice to you, make no mistake. The regulatory standards are there to ensure quality, and this point alone is enough to undermine the validity of this drug. I want to stress this because it is unacceptable to have such poor manufacturing processes; you deserve better for giving your lives to participate in the trials and advocating so strongly for its approval. It really pains me to know that a poor quality product has been given to patients. This is not, and never will be acceptable, and this point alone, from a regulatory perspective, is sufficient to deny approval. I am truly disappointed that Brainstorm did not do enough to ensure the quality and manufacturing process of this drug was adequate, because it only serves to harm the data and potentially harm patients.
Second, the absence of preclinical data to support the proposed mechanism of action is another failure and disservice to you. Before a trial even begins, there should be clear and substantial scientific data to support the intended mechanism of action. Without this, it’s like taking a shot in the dark. No convincing arguments were put forward today to support how the drug works. It is not enough to claim that it works by secreting NTFs and immuno modulation, without proving that this is the case and that this approach yields benefit in preclinical models. This is truly disappointing for me to hear as a scientist and as a physician. How can we ever expect the results to be clear when key basic questions remain unanswered? It is not enough to assume a cocktail of NFTs is beneficial, and the minute levels of various NFTs in the CSF following administration, seriously questions how the drug could ever be effective. No data was presented to prove that MCS adhere to the spinal cord and therefore we are unable to know whether they are located in then right place. This is a disservice to you, as there should be no doubts over such fundamental aspects of the drug such as it’s mechanism of action, site of action and persistence in vivo. Without this, how can we ever justify this drug fulfils it’s intended purpose? You deserve better than this and is another major disappointment from Brainstorm.
Next comes efficacy. I hear the testimonies loud and clear, and I do not doubt them. We clearly know very little about this drug and perhaps all the elements aligned in some instances to provide an effect. But the data clearly shows that such an effect is not reproducible, consistent or identifiable within a plausible subset of patients. I do believe that the future of ALS treatment will be far more tailored, and that we are unlikely to end up with a one size fits all approach. This is why we need far better ways of stratifying patients according to their underlying biology, not arbitrary characteristics such as fast or slow, or early or late. Back to the efficacy, the unbiased analysis from the FDA clearly shows negative results from 2 randomised controlled studies on all primary and secondary endpoints. We can debate the adequacy or acceptability of post-hoc analyses, but this must always be taken with caution and such analyses do not make up for otherwise negative pre-specified data.
The data presented is not convincing, and it never was which is why the FDA rejected the BLA on 2 occasions and promoted the Sponsor for more. Instead Brainstorm wasted FOUR YEARS to get us to this day today, instead of hearing the message and doing more to validate this drug. This is a disservice to you. I understand financial constraints may have limited the ability to perform another trial, but that is not a sufficient excuse to persist with negative data and apply statistical methods to look for a signal and exploit patients for years in the process. You deserve better than this. The outcome today was predictable, and the community has been played with for years with hope that something positive might happen today. This is wrong on so many levels and has been difficult for me to reconcile. We must honour your lives, efforts and families every step of the way. We must never exploit your generosity and commitment to research and we must never subject you to bad science or poor quality drugs. There is no credibility if any of that takes place and I am so disappointed that this battle has lingered on for years when your lives and all the resources poured into this program could have been used elsewhere. I fully understand the level of risk ALS patients are willing to take on and I applaud the bravery, but this makes you vulnerable and this should NEVER be exploited. The increased mortality in the treated group is a major concern and was not accounted for in any way. This treatment may have harmed you more than doing good and I cannot accept that.
I care deeply about ALS patients and the community and I hope you can see that. I want to see effective treatments come to life and I am committed to contributing to that as best as I can throughout my career. You truly deserve better than this and we should not applaud Brainstorm. We should be holding them accountable for the inadequacy presented today
