Below is an e-mail that Donna sent out to the HPS Network listservs. I know some of you choose not to join the listservs, but you do follow the blog to keep up with HPS related stuff. As you might imagine, I have a lot to blog about this, and I'll be posting that soon - but for those that don't know, I just wanted to give you the information and a chance to digest it.
Dear All,
This is a difficult email to write. We needed to wait until the participants were all notified, therefore many of you know the status of the protocol already.
Dr. Gahl called a while back to explain what the DSMB (Data Safety Monitoring Board ) had discovered when they reviewed the pirfenidone drug trial. Initially, they had decided that we needed to enroll more people to make the data significant. At that time, Dr. Markello had called and we accepted the challenge of finding 17 more participants. It is my understanding that when the DSMB was notified that we would keep enrolling they continued to evaluate the protocol.
When they looked at the PFT results of the people that were on Pirfenidone compared to the PFT results of the people that were on placebo, they did not see a statistical difference. Dr. Gahl explained that while he thinks that the drug is somewhat (though mildly) helpful, and definitely safe to give, the reason why they did not see a statistical difference is because a majority of people were not declining at the rate that was expected. If you remember, we did this trial in 1998 – 2000 and in that trial the participants had an FVC that was lower at the starting point. This trial, the second trial, was designed to medicate people earlier so the entrance criteria was an FVC of 85% or lower. This meant that the individuals in this second protocol were actually healthier than those in the first protocol. It also meant that the expected rate of decline in persons enrolled in the second protocol were based on the information garnered from the first protocol, or in other words, the rate of decline of the more affected persons. Without having prior studies done on individuals in the higher range ie. FVC say 70-85%, it was presumed that they would begin to decline similarly to the lower group. When this did not happen the study was unable to prove that pirfenidone was making a statistically significant difference.
Therefore, Dr. Gahl was advised to close the study. He wrote for us some taking points that he wanted me to share with you all.
1. On August 11, 2009, we learned that our clinical trial of pirfenidone for the lung fibrosis of HPS could never show that pirfenidone was helpful at slowing the progression of the disease. We were directed to stop the study, and that is what we are now doing.
2. This does not necessarily mean that pirfenidone does not work, just that our study could not prove that it works.
3. We believe that the reason for this outcome is that the patients enrolled in our study had such mild disease that, even if pirfenidone stopped all progression of the fibrosis, we could not detect a difference for many years.
4. In addition, the patients enrolled in this study did better than predicted, perhaps because of the superb care provided by Kevin O’Brien, Dr. Gochuico, and Dr. Markello.
5. The study did demonstrate safety of pirfenidone in this group of patients.
6. Going forward, we will continue to devote our efforts to determining the basis for the lung disease of HPS, trying to develop a treatment directed against the primary problem causing the fibrosis
He wanted me to be sure to tell you that he is continuing his dedication to help us. He feels hopeful that it will free up more time to get to the bottom of HPS. He also mentioned that pirfenidone was never the cure and it would have been terrible if we worked on finding the 17 more people and then spent years to find that it was not dramatically helpful. I know that Dr. Gahl, Dr. Markello, Kevin, Dr. Gochuico, Jose and the rest are all really sad.
Personally, I recall the fight that we had for three years, back in 2000, trying to get the drug back. Dr. Gahl was relentless and unwavering then and I believe that’s the only way he knows how to be.
My heart is breaking for those who were on the protocol. We owe them a huge amount of gratitude for the work that they have done on behalf of all of us. I also am amazed at our caring community who waited until all the participants were told before saying anything. The Puerto Rico group had to deal with this news in their hearts a day before they put on a tremendous conference. I am so proud of all of you and it is an honor to work with you. It is all the love in the Network that keeps it going.
Dear All,
This is a difficult email to write. We needed to wait until the participants were all notified, therefore many of you know the status of the protocol already.
Dr. Gahl called a while back to explain what the DSMB (Data Safety Monitoring Board ) had discovered when they reviewed the pirfenidone drug trial. Initially, they had decided that we needed to enroll more people to make the data significant. At that time, Dr. Markello had called and we accepted the challenge of finding 17 more participants. It is my understanding that when the DSMB was notified that we would keep enrolling they continued to evaluate the protocol.
When they looked at the PFT results of the people that were on Pirfenidone compared to the PFT results of the people that were on placebo, they did not see a statistical difference. Dr. Gahl explained that while he thinks that the drug is somewhat (though mildly) helpful, and definitely safe to give, the reason why they did not see a statistical difference is because a majority of people were not declining at the rate that was expected. If you remember, we did this trial in 1998 – 2000 and in that trial the participants had an FVC that was lower at the starting point. This trial, the second trial, was designed to medicate people earlier so the entrance criteria was an FVC of 85% or lower. This meant that the individuals in this second protocol were actually healthier than those in the first protocol. It also meant that the expected rate of decline in persons enrolled in the second protocol were based on the information garnered from the first protocol, or in other words, the rate of decline of the more affected persons. Without having prior studies done on individuals in the higher range ie. FVC say 70-85%, it was presumed that they would begin to decline similarly to the lower group. When this did not happen the study was unable to prove that pirfenidone was making a statistically significant difference.
Therefore, Dr. Gahl was advised to close the study. He wrote for us some taking points that he wanted me to share with you all.
1. On August 11, 2009, we learned that our clinical trial of pirfenidone for the lung fibrosis of HPS could never show that pirfenidone was helpful at slowing the progression of the disease. We were directed to stop the study, and that is what we are now doing.
2. This does not necessarily mean that pirfenidone does not work, just that our study could not prove that it works.
3. We believe that the reason for this outcome is that the patients enrolled in our study had such mild disease that, even if pirfenidone stopped all progression of the fibrosis, we could not detect a difference for many years.
4. In addition, the patients enrolled in this study did better than predicted, perhaps because of the superb care provided by Kevin O’Brien, Dr. Gochuico, and Dr. Markello.
5. The study did demonstrate safety of pirfenidone in this group of patients.
6. Going forward, we will continue to devote our efforts to determining the basis for the lung disease of HPS, trying to develop a treatment directed against the primary problem causing the fibrosis
He wanted me to be sure to tell you that he is continuing his dedication to help us. He feels hopeful that it will free up more time to get to the bottom of HPS. He also mentioned that pirfenidone was never the cure and it would have been terrible if we worked on finding the 17 more people and then spent years to find that it was not dramatically helpful. I know that Dr. Gahl, Dr. Markello, Kevin, Dr. Gochuico, Jose and the rest are all really sad.
Personally, I recall the fight that we had for three years, back in 2000, trying to get the drug back. Dr. Gahl was relentless and unwavering then and I believe that’s the only way he knows how to be.
My heart is breaking for those who were on the protocol. We owe them a huge amount of gratitude for the work that they have done on behalf of all of us. I also am amazed at our caring community who waited until all the participants were told before saying anything. The Puerto Rico group had to deal with this news in their hearts a day before they put on a tremendous conference. I am so proud of all of you and it is an honor to work with you. It is all the love in the Network that keeps it going.
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