The FDA Advisory Committee meeting to look at Jazz’s request to market sodium oxybate for the treatment of fibromyalgia was fascinating. I originally planned to just go for the public comment hour, but ended up staying and I am glad I did. I kind of wish I had gone for the morning presentation by Jazz – pharmaceutical companies are quite slick – it was fun to see them responding to the afternoon clarifying questions from the committee. But I did get a copy of their slides – Dr. Russell and Dr. Spaeth spoke as part of the Jazz presentations. The background materials are available on the FDA website, and seems to include the same information in the slides, but presented differently.
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisDrugsAdvisoryCommittee/ucm222886.htm
The audience was an interesting mix of financial/stock suits, press, pharma suits, a few doctors, and only a very few lay people and/or people with FM, that I could tell. Jazz paid travel expenses for several of the patients who testified, but not all. They clearly chose carefully – lovely, articulate, professional women with incredibly compelling stories of how sodium oxybate gave them a normal life after years of suffering with inferior treatments for their FM symptoms. If I am remembering right, only two people spoke out AGAINST approval (one from Project GHB and another from a drug treatment center in CA). Only three Mds spoke at the public comment – Mohammad Yunus and Victor Rosenfeld (and a few of his patients spoke as well), and Evan Ekman. I talked to a few of the women who spoke after the vote. They were quick to tell me that sodium oxybate changed their lives and that there were sad to think others may not get the opportunity to try it if the FDA doesn’t approve it, since many insurance companies won’t cover it now.
As a side note – I called my health insurance company and they indicated that they would cover Xyrem, regardless of the diagnosis my physician indicated it for, with a $35 copay. So I hope that patients who feel that this treatment may help them will pursue it with their doctors and insurance companies, even if the FDA doesn’t approve it specifically as a treatment for fibromyalgia.
I decided to stay for the clarifying questions and discussion when I realized that they would be voting – was curious. A few members monopolized the discussion. The risks of diversion creating an epidemic of GHB abuse was a predominant theme. No one seemed to question that the research gave sufficient evidence that treatment was effective for FM for pain and fatigue (tho they seemed to be hung up that there was not sufficient evidence for sleep improvement, however, which I found ironic). Several kept quoting the “5 million people with fibromyalgia” figure as evidence that there would be insufficient measures to keep the drug under strict control, since the potential user base is so much larger than for narcolepsy.
My takeaway from it all is that if Jazz wants to impress the FDA they need to find a way to more clearly define a distinct population of patients who might benefit from sodium oxybate. I think further research should identify why some people are responders and other non-responders. In the discussion session, Shelden Kapen, brought up the lack of imaging data. I presume he meant he would have liked data to identify or clarify differences, either to measure efficacy or patient population differences. I think that was his idea. He brought up the need for more data to show how slow wave sleep correlates with changes in FM symptoms (he cited Moldofsky and Van Cauter.
Clearly, the broad definition of what is an FM patient, even using the new standards to define a cohort for clinical trials that researchers have come up with, does not help. Another person brought up the need to more clearly identify the subgroups of FM patients (I think it was Dr. Richard Denisco of NIH).
I think Jazz needs to clearly find evidence to explain WHY certain patients respond to sodium oxybate treatment where pregabalin (Lyrica) or Cymbalta, for example may have failed to provide substantial relief. This way the patient population that could be prescribed the drug would be more discreet (not the potential 5 million that freaked some of the committee). Jazz was quick and eager to respond to the recurring sentiment of the panel about the huge population of potential users of this treatment. The say they estimate a potential population of patients who would consider use of the drug at 120,000.
What I am still unclear about it whether the responders in the clinical trials also had sleep disorders as part of their constellation of FM symptoms. Dr. Spitzer’s recent paper talks about something he calls ”Narcoleptiform Sleep Disorder” I wonder if it is the people who have this that are the ones who are the subset of FM patients who would do well on sodium oxybate.
Obviously, the identification of subgroups could be a much bigger issue for all FM research. The diagnostic criteria encompasses such a large group of patients. But we all know from experience that there are differences among FM patients and the symptoms we present with can vary widely, and treatments currently available have a similar wide variety of responders.
http://www.ncbi.nlm.nih.gov/pubmed/20461783 The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.
http://www.ncbi.nlm.nih.gov/pubmed/19820221 Fibromyalgia syndrome module at OMERACT 9: domain construct.
The two yes votes were Dennis Dixon, statistician from NIH, who remarked “efficacy has been shown ... the results are impressive ... safety measures acceptable ... side effect minimal,” and Richard Meisch, MD from U of Texas who simply said “benefits outweigh the risks” when explaining his yes vote. So, that is my report. Hope you found it interesting!
I admit that I cried during some of the public testimony - I could really relate to their stories and was so happy that they had found a solution that worked for them. I recorded some of the public comment and posted it if you have any interest: http://littlebirdexpress.tumblr.com/post/987729377/public-comment-audio-for-fda-advisory-meeting-sodium
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisDrugsAdvisoryCommittee/ucm222886.htm
The audience was an interesting mix of financial/stock suits, press, pharma suits, a few doctors, and only a very few lay people and/or people with FM, that I could tell. Jazz paid travel expenses for several of the patients who testified, but not all. They clearly chose carefully – lovely, articulate, professional women with incredibly compelling stories of how sodium oxybate gave them a normal life after years of suffering with inferior treatments for their FM symptoms. If I am remembering right, only two people spoke out AGAINST approval (one from Project GHB and another from a drug treatment center in CA). Only three Mds spoke at the public comment – Mohammad Yunus and Victor Rosenfeld (and a few of his patients spoke as well), and Evan Ekman. I talked to a few of the women who spoke after the vote. They were quick to tell me that sodium oxybate changed their lives and that there were sad to think others may not get the opportunity to try it if the FDA doesn’t approve it, since many insurance companies won’t cover it now.
As a side note – I called my health insurance company and they indicated that they would cover Xyrem, regardless of the diagnosis my physician indicated it for, with a $35 copay. So I hope that patients who feel that this treatment may help them will pursue it with their doctors and insurance companies, even if the FDA doesn’t approve it specifically as a treatment for fibromyalgia.
I decided to stay for the clarifying questions and discussion when I realized that they would be voting – was curious. A few members monopolized the discussion. The risks of diversion creating an epidemic of GHB abuse was a predominant theme. No one seemed to question that the research gave sufficient evidence that treatment was effective for FM for pain and fatigue (tho they seemed to be hung up that there was not sufficient evidence for sleep improvement, however, which I found ironic). Several kept quoting the “5 million people with fibromyalgia” figure as evidence that there would be insufficient measures to keep the drug under strict control, since the potential user base is so much larger than for narcolepsy.
My takeaway from it all is that if Jazz wants to impress the FDA they need to find a way to more clearly define a distinct population of patients who might benefit from sodium oxybate. I think further research should identify why some people are responders and other non-responders. In the discussion session, Shelden Kapen, brought up the lack of imaging data. I presume he meant he would have liked data to identify or clarify differences, either to measure efficacy or patient population differences. I think that was his idea. He brought up the need for more data to show how slow wave sleep correlates with changes in FM symptoms (he cited Moldofsky and Van Cauter.
Clearly, the broad definition of what is an FM patient, even using the new standards to define a cohort for clinical trials that researchers have come up with, does not help. Another person brought up the need to more clearly identify the subgroups of FM patients (I think it was Dr. Richard Denisco of NIH).
I think Jazz needs to clearly find evidence to explain WHY certain patients respond to sodium oxybate treatment where pregabalin (Lyrica) or Cymbalta, for example may have failed to provide substantial relief. This way the patient population that could be prescribed the drug would be more discreet (not the potential 5 million that freaked some of the committee). Jazz was quick and eager to respond to the recurring sentiment of the panel about the huge population of potential users of this treatment. The say they estimate a potential population of patients who would consider use of the drug at 120,000.
What I am still unclear about it whether the responders in the clinical trials also had sleep disorders as part of their constellation of FM symptoms. Dr. Spitzer’s recent paper talks about something he calls ”Narcoleptiform Sleep Disorder” I wonder if it is the people who have this that are the ones who are the subset of FM patients who would do well on sodium oxybate.
Obviously, the identification of subgroups could be a much bigger issue for all FM research. The diagnostic criteria encompasses such a large group of patients. But we all know from experience that there are differences among FM patients and the symptoms we present with can vary widely, and treatments currently available have a similar wide variety of responders.
http://www.ncbi.nlm.nih.gov/pubmed/20461783 The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.
http://www.ncbi.nlm.nih.gov/pubmed/19820221 Fibromyalgia syndrome module at OMERACT 9: domain construct.
The two yes votes were Dennis Dixon, statistician from NIH, who remarked “efficacy has been shown ... the results are impressive ... safety measures acceptable ... side effect minimal,” and Richard Meisch, MD from U of Texas who simply said “benefits outweigh the risks” when explaining his yes vote. So, that is my report. Hope you found it interesting!
I admit that I cried during some of the public testimony - I could really relate to their stories and was so happy that they had found a solution that worked for them. I recorded some of the public comment and posted it if you have any interest: http://littlebirdexpress.tumblr.com/post/987729377/public-comment-audio-for-fda-advisory-meeting-sodium
