What if MASAC?
A few of my readers, primarily those not residing in the US, have asked what is MASAC? The acronym stands for Medical And Scientific Advisory Committee. Per the National Hemophilia Foundation (NHF), a national US based organization, MASAC was developed to advance clinical care and promote hemophilia research. You can read more about MASAC's role and its previous recommendations here.
MASAC on SIPPET
Over the past 7 months the hemophilia community speculated on what the SIPPET study was and what its results really meant to them. Now MASAC is here with its recommendations on SIPPET in MASAC document # 243.
Here are some of the fundamental facts based which I make my comment:
In the season of disclaimers and disclosures, I have the following claimer: These are solely my opinions. I have not received any funds from plasma-derived or recombinant product manufacturers to express my thoughts.
So let's get right to it. Like everyone else who is SIPPET-aware in the hemophilia community, I too waited to hear what MASAC had to say. Initially, I had set very high expectations for MASAC. I expected a clear-cut opinion - If you fall in this category... do this, else do that. Very quickly, I lowered my sights. I suspected MASAC could not show a preference of one product over another. Very fair. Then how would they respond to increased incidence of inhibitors using recombinant products.
They released a statement on Jun 28, 2016. Here are the bullets from MASACs recommendation and in italics are my thoughts.
MASAC Recommendations
Based on currently available evidence, MASAC makes the following recommendations:
1. Individuals with greater than 50 exposure days (ED) to any recombinant product (i.e. Previously
Treated Patients or PTPs) should consider remaining on their current product, since multiple
clinical studies have shown that their risk for inhibitor development with any FVIII product is
markedly diminished after 50 EDs
Well, I fall in this category. Here the indication is to not 'rock the boat'. If you are treating with product X, stay with the same. Sounds good to me and in line with my plans. I am also delighted to know that my chances of developing an inhibitor is low to none. All round good news for me. But then what about that new product that has a longer half-life; the one in the horizon that is injected subcutaneously; the one with a cryptic name, ALN-AT3 (reminded me of R2-D2). There are numerous products in the works (a.k.a pipeline). If someone such as me, stays on his/her product based on MASAC, who would be on the new products. PUPs? At my clinic visit my hematologist shares her experience with new products and recommends a me to switch. Should I? What if I develop an inhibitor after the switch? Can my hematologist answer this question, can MASAC? Clearly, the answer is 'maybe not'. Inhibitors are truly an unknown. I do not believe that predisposition to inhibitors is geographic or ethnic.
2. Individuals with more than zero and less than 50 exposure days should consider staying on
their current recombinant FVIII product, since the differences between SIPPET and
numerous other studies may not warrant switching patients who have already initiated a
treatment regimen.
Once again, if I understand this guideline, no product switch is recommended (' consider staying on their current recombinant FVIII product') to this group of patients. Then who gets to try out the products in the pipeline? PUPs, again? MASAC document states "PUP studies have been published for each new FVIII product introduced to the market in the past 25 years.". Has this data been shared with the consumer- either by the manufacturer or the national organizations (NHF, HFA). Is it hosted online for me to view. Such data would help me and many others like me choose a product to switch to. This bullet also directly addresses 'current recombinant FVIII product' users. What is recommended to non-recombinant users, having less than 50 exposure days? I would like to see MASAC address this population.
3. Newly diagnosed individuals and their caregivers should consider the new data from the
SIPPET study in the context of all the accumulated data on inhibitor formation in PUPs and
the pathogen safety risk/benefit of the two product classes and consider the following
options:
a. Initiate therapy with a pdFVIII/VWF product in all PUPs.
b. Initiate therapy with a rFVIII product as previously recommended by MASAC (6).
c. Initiate therapy with a newer rFVIII product.
For once, MASAC's recommendation is clear to me with 3 (a). All PUPs 'treat with pdFVIII/VWF product '. MASAC members have spoken and given good direction, based on the cumulative wisdom gathered from the universe of hemophilia research and their own medical experiences, weighing in on the results from SIPPET. I was excited to read this. Then, it got murky with 3(b) and 3(c). What is MASAC really recommending to PUPs or 'Newly diagnosed individuals'. Is it pdFVIII/VWF or is it rFVIII or is it R2-D2, ACE910 (new products)? If they are indeed saying that PUPs pick any product have they really considered the results from the SIPPET study. Perhaps they are waiting for a similar study exclusively on US based patients.
The referenced document (6) in 3(b) is titled:
6. MASAC Recommendation regarding the use of recombinant clotting factor products with
respect to pathogen transmission. MASAC Document #169, 2006
I have always known recombinant products to be safer than plasma-derived. MASAC does acknowledge this fact, though it also cautions us on the potential transmission of the new and emerging viruses such as Zika, SARS in a pdFVIII/VWF product. So, once again, is MASAC saying that these viruses could pass through the manufacturing stages, in theory, and infect? So now has it come down to the debate of choosing between Inhibitors vs. virus, for PUPs and newly diagnosed? Who will take the final decision? The family of the PUP who in all likelihood knows very little about these nuances OR the medical team? If it is the medical team, for the care to be standardized across treatment centers they will need clearer direction from MASAC or data from prospective studies. Perhaps MASAC is looking for additional SIPPET-like clinical trials conducted in the US before they can do this (I know I am repeating this). For now, recommending 3(b) and 3(c) alongside 3(a) to PUPs is confusing.
4. Regardless of which option is chosen, all PUPs should be enrolled in the ATHN data collection system or a clinical trial to assess outcomes.
As I alluded to above is data collection through HTCs for ATHN being analyzed for new inhibitor development as part of a clinical trial. If so, then there is data available from US based studies and MASAC can release a statement on it. Such a report, even if interim, would promote willingness in the community to enroll PUPs. If not, then it is simply a reminder to enroll PUPs and has little to do with 'MASAC on SIPPET'.
5. For all classes of treatment products, the risk for inhibitor formation in PUPs is unacceptably high. All efforts by government, HTCs, patient advocates, and industry should be directed at reducing the risk of inhibitor formation.
I agree here. An incidence of inhibitors, even at 26.8%, is too high a number, with a lot of implications. There are products in the horizon which help clotting in inhibitor patients by bypassing inhibitors. These are exciting times as Dr. Glenn Pierce wrote in PEN magazine.
In Summary
With this document MASAC have covered all patients under their oversight who receive FVIII products- PUPs and non-PUPs. They agree that inhibitors have been on the rise since the introduction of recombinant products in 1992. They attribute this to closer monitoring of inhibitor development and more sensitive assays since the 90s. They acknowledge that the SIPPET study was across a diverse patient population while previous, similar studies were in primarily "Caucasians". SIPPET has studied only a small number of patients (16%) on 3rd generation recombinant product, which a majority of the US based patients are such products, recommending that the community do not extrapolate the SIPPET results to newer and in-pipeline products.
They have stated also that all new products are studied on PUPs. Where is this data? Were inhibitor development studied over 50 exposure doses? MASAC points to the fact that in the SIPPET study did not follow patients after 50 EDs. Well, the study was terminated prematurely due to a World Federation of Hemophilia announcement to consider not using Kogenate FS, for newly diagnosed patients with Hemophilia A, when other, safer, clotting-factor concentrates are available. This was due to higher risk of inhibitors.
MASAC suggests that 'risk of inhibitor development must be weighed against transmission of pathogens via pdFVIII/VWF'. Here they are re-stating the obvious- do a risk-benefit analysis. But, who does this analysis? Is it the patient? How does he/she figure this out if he/she plans to switch to a newer product. If it is the doctor, does he have all the inhibitor development data to faithfully perform this analysis? I am aware of a few new products available to me to switch to right now or coming soon. Where do I find the information I need to make the decision to switch with confidence?
If you, my reader, has similar or additional questions or answers I'd love to hear from you in the comments section below or in an email.
EHC on SIPPET
A few of my readers, primarily those not residing in the US, have asked what is MASAC? The acronym stands for Medical And Scientific Advisory Committee. Per the National Hemophilia Foundation (NHF), a national US based organization, MASAC was developed to advance clinical care and promote hemophilia research. You can read more about MASAC's role and its previous recommendations here.
MASAC on SIPPET
Over the past 7 months the hemophilia community speculated on what the SIPPET study was and what its results really meant to them. Now MASAC is here with its recommendations on SIPPET in MASAC document # 243.
Here are some of the fundamental facts based which I make my comment:
- SIPPET studied only toddlers with Hemophilia A (Factor VIII deficiency)
- SIPPET studied only previously untreated patients (PUPs).
- Only 18 of 251 PUPs studied were from the US.
- MASAC as an advisory committee is part of the National Hemophilia Foundation (NHF), a US based national organization. MASAC makes recommendations for patient care in the US.
- I have Hemophilia A, am 55 years old, without inhibitor (never had one). I have used recombinant FVIII for over 20 years.
In the season of disclaimers and disclosures, I have the following claimer: These are solely my opinions. I have not received any funds from plasma-derived or recombinant product manufacturers to express my thoughts.
So let's get right to it. Like everyone else who is SIPPET-aware in the hemophilia community, I too waited to hear what MASAC had to say. Initially, I had set very high expectations for MASAC. I expected a clear-cut opinion - If you fall in this category... do this, else do that. Very quickly, I lowered my sights. I suspected MASAC could not show a preference of one product over another. Very fair. Then how would they respond to increased incidence of inhibitors using recombinant products.
They released a statement on Jun 28, 2016. Here are the bullets from MASACs recommendation and in italics are my thoughts.
MASAC Recommendations
Based on currently available evidence, MASAC makes the following recommendations:
1. Individuals with greater than 50 exposure days (ED) to any recombinant product (i.e. Previously
Treated Patients or PTPs) should consider remaining on their current product, since multiple
clinical studies have shown that their risk for inhibitor development with any FVIII product is
markedly diminished after 50 EDs
Well, I fall in this category. Here the indication is to not 'rock the boat'. If you are treating with product X, stay with the same. Sounds good to me and in line with my plans. I am also delighted to know that my chances of developing an inhibitor is low to none. All round good news for me. But then what about that new product that has a longer half-life; the one in the horizon that is injected subcutaneously; the one with a cryptic name, ALN-AT3 (reminded me of R2-D2). There are numerous products in the works (a.k.a pipeline). If someone such as me, stays on his/her product based on MASAC, who would be on the new products. PUPs? At my clinic visit my hematologist shares her experience with new products and recommends a me to switch. Should I? What if I develop an inhibitor after the switch? Can my hematologist answer this question, can MASAC? Clearly, the answer is 'maybe not'. Inhibitors are truly an unknown. I do not believe that predisposition to inhibitors is geographic or ethnic.
2. Individuals with more than zero and less than 50 exposure days should consider staying on
their current recombinant FVIII product, since the differences between SIPPET and
numerous other studies may not warrant switching patients who have already initiated a
treatment regimen.
Once again, if I understand this guideline, no product switch is recommended (' consider staying on their current recombinant FVIII product') to this group of patients. Then who gets to try out the products in the pipeline? PUPs, again? MASAC document states "PUP studies have been published for each new FVIII product introduced to the market in the past 25 years.". Has this data been shared with the consumer- either by the manufacturer or the national organizations (NHF, HFA). Is it hosted online for me to view. Such data would help me and many others like me choose a product to switch to. This bullet also directly addresses 'current recombinant FVIII product' users. What is recommended to non-recombinant users, having less than 50 exposure days? I would like to see MASAC address this population.
3. Newly diagnosed individuals and their caregivers should consider the new data from the
SIPPET study in the context of all the accumulated data on inhibitor formation in PUPs and
the pathogen safety risk/benefit of the two product classes and consider the following
options:
a. Initiate therapy with a pdFVIII/VWF product in all PUPs.
b. Initiate therapy with a rFVIII product as previously recommended by MASAC (6).
c. Initiate therapy with a newer rFVIII product.
For once, MASAC's recommendation is clear to me with 3 (a). All PUPs 'treat with pdFVIII/VWF product '. MASAC members have spoken and given good direction, based on the cumulative wisdom gathered from the universe of hemophilia research and their own medical experiences, weighing in on the results from SIPPET. I was excited to read this. Then, it got murky with 3(b) and 3(c). What is MASAC really recommending to PUPs or 'Newly diagnosed individuals'. Is it pdFVIII/VWF or is it rFVIII or is it R2-D2, ACE910 (new products)? If they are indeed saying that PUPs pick any product have they really considered the results from the SIPPET study. Perhaps they are waiting for a similar study exclusively on US based patients.
The referenced document (6) in 3(b) is titled:
6. MASAC Recommendation regarding the use of recombinant clotting factor products with
respect to pathogen transmission. MASAC Document #169, 2006
I have always known recombinant products to be safer than plasma-derived. MASAC does acknowledge this fact, though it also cautions us on the potential transmission of the new and emerging viruses such as Zika, SARS in a pdFVIII/VWF product. So, once again, is MASAC saying that these viruses could pass through the manufacturing stages, in theory, and infect? So now has it come down to the debate of choosing between Inhibitors vs. virus, for PUPs and newly diagnosed? Who will take the final decision? The family of the PUP who in all likelihood knows very little about these nuances OR the medical team? If it is the medical team, for the care to be standardized across treatment centers they will need clearer direction from MASAC or data from prospective studies. Perhaps MASAC is looking for additional SIPPET-like clinical trials conducted in the US before they can do this (I know I am repeating this). For now, recommending 3(b) and 3(c) alongside 3(a) to PUPs is confusing.
4. Regardless of which option is chosen, all PUPs should be enrolled in the ATHN data collection system or a clinical trial to assess outcomes.
As I alluded to above is data collection through HTCs for ATHN being analyzed for new inhibitor development as part of a clinical trial. If so, then there is data available from US based studies and MASAC can release a statement on it. Such a report, even if interim, would promote willingness in the community to enroll PUPs. If not, then it is simply a reminder to enroll PUPs and has little to do with 'MASAC on SIPPET'.
5. For all classes of treatment products, the risk for inhibitor formation in PUPs is unacceptably high. All efforts by government, HTCs, patient advocates, and industry should be directed at reducing the risk of inhibitor formation.
I agree here. An incidence of inhibitors, even at 26.8%, is too high a number, with a lot of implications. There are products in the horizon which help clotting in inhibitor patients by bypassing inhibitors. These are exciting times as Dr. Glenn Pierce wrote in PEN magazine.
In Summary
With this document MASAC have covered all patients under their oversight who receive FVIII products- PUPs and non-PUPs. They agree that inhibitors have been on the rise since the introduction of recombinant products in 1992. They attribute this to closer monitoring of inhibitor development and more sensitive assays since the 90s. They acknowledge that the SIPPET study was across a diverse patient population while previous, similar studies were in primarily "Caucasians". SIPPET has studied only a small number of patients (16%) on 3rd generation recombinant product, which a majority of the US based patients are such products, recommending that the community do not extrapolate the SIPPET results to newer and in-pipeline products.
They have stated also that all new products are studied on PUPs. Where is this data? Were inhibitor development studied over 50 exposure doses? MASAC points to the fact that in the SIPPET study did not follow patients after 50 EDs. Well, the study was terminated prematurely due to a World Federation of Hemophilia announcement to consider not using Kogenate FS, for newly diagnosed patients with Hemophilia A, when other, safer, clotting-factor concentrates are available. This was due to higher risk of inhibitors.
MASAC suggests that 'risk of inhibitor development must be weighed against transmission of pathogens via pdFVIII/VWF'. Here they are re-stating the obvious- do a risk-benefit analysis. But, who does this analysis? Is it the patient? How does he/she figure this out if he/she plans to switch to a newer product. If it is the doctor, does he have all the inhibitor development data to faithfully perform this analysis? I am aware of a few new products available to me to switch to right now or coming soon. Where do I find the information I need to make the decision to switch with confidence?
If you, my reader, has similar or additional questions or answers I'd love to hear from you in the comments section below or in an email.
EHC on SIPPET
The European Haemophilia Consortium (EHC) has 45 National Member Organisations (NMOs) from 27 Member States of the European Union (EU) and most Member States of the Council of Europe. Simplified, EHC is the NHF equivalent of the EU. EHC has posted their own response to the SIPPET study here.
Brexit impact on hemophilia care in Europe
The European Association for Haemophilia and Allied Disorders (EAHAD) is a multi-disciplinary association of healthcare professionals who provide care for individuals with haemophilia and other bleeding disorders. Its members include hematologists, nurses, physiotherapists, laboratory scientists and researchers from across Europe. The Brexit vote on June 24, 2016 and UK's decision to part from the EU could have an impact on collaborations between the different member states and UK. To minimize this impact the president of EAHAD published this letter on June 28, 2016.
Next post: What does SIPPET mean to the developing world? Who is a PUP in the developing world?
Brexit impact on hemophilia care in Europe
The European Association for Haemophilia and Allied Disorders (EAHAD) is a multi-disciplinary association of healthcare professionals who provide care for individuals with haemophilia and other bleeding disorders. Its members include hematologists, nurses, physiotherapists, laboratory scientists and researchers from across Europe. The Brexit vote on June 24, 2016 and UK's decision to part from the EU could have an impact on collaborations between the different member states and UK. To minimize this impact the president of EAHAD published this letter on June 28, 2016.
Next post: What does SIPPET mean to the developing world? Who is a PUP in the developing world?
No comments:
Post a Comment