I just returned from a meeting in Europe and one of the best things about these meetings is hearing stories of families, listening to experiences, and learning about those special times when a child’s insight makes us stop in our tracks. It is not about criticism or what is wrong, right, or in between. It is just about those times when we find our hearts’ making a recording that we will remember all the days of our life.
One mom talked about all the things she was doing for her son. She described a pretty time consuming schedule that included supplements, stretching exercises, aqua therapy, as well as a very strict diet. It was pretty amazing really and I had the sense that she had achieved the perfect “10” as a mom, someone we would all look up to and wonder just how she fits everything into a 24-hour period or if she found some magic to stretch the few hours in a day. All of a sudden in the middle of her story, she had tears in her eyes as she talked about one particular evening when her son was grumpy as she started the stretching exercises. He had had a full day. As she started his stretches, he started crying. She asked if the stretch was painful. He said ‘no.’ Like all of us, she probed, asking if something went wrong at school, if his stomach was upset, if he was in pain, looking for something, anything to understand the tears. We have a natural tendency to try to ‘fix’ everything. He simply said he did not want to do the stretching tonight. With that, her fear increased and she tried to sooth him, tell him how important this was for his muscles, how much she was doing to help him. And in that very simple way that children have, he said, “You are not doing this for me, I am doing this for you.” She felt her heart breaking.
I also spoke with a father whose son is now in college. He discussed his son’s detailed agenda to include a variety of interventions squeezed in between college classes and studies. I asked about friends, about movies, about music, about laughter. This father said all that would come later. I wondered when ‘later’ was planned. This father was so worried that if something interrupted their rigid schedule, his son would lose function. He felt this regimen was essential to maintain the life his son had, the things his son was able to do at this very moment. One glitch, one change, and it would fall apart.
I remember hanging on for dear life, thinking that if I changed one thing, if I took time to breathe, time off, time to enjoy something or some activity from my previous life, things would fall apart. It felt like my life was hanging on a thread. I remember hanging everything on the future. I started sentences with ‘when this happens,’ thinking that a certain clinical trial would yield amazing results and then we would catch up on whatever it was that we missed.
Every once in a while, I think it is good to take a step back and remember, the life we are living is not a dress rehearsal, it is the real deal. There are no ‘do overs’ and no way to recover time lost. So, while we are all aggressively pursuing what we think is the best route for our sons and daughters, it is important to listen to their voice, to ensure the discipline of care includes their perspective and their opinions.
And as you make up the schedule, please include 30 minutes of laughter. It should be considered a therapeutic intervention!
Tuesday, June 15, 2010
Thursday, June 10, 2010
Washington Week in Review
Did I miss Spring? I spent the last week of May in Washington, DC. I had meetings on Monday and Tuesday centered around regulatory issues (FDA and OOPD), compounds, small clinical trials, webinars, and workshops in the planning stages and tossing around some ideas about how to design new models for trials, or how we might encourage companies to think a bit outside the box. Discussions like this are like taking a breath of fresh air into your lungs. I find them invigorating, hopeful, and promising, incredibly thankful to see the results of our early investments in research now move from the bench to the bedside . On the other side, I realize nothing will ever move fast enough for our boys.
By midweek, the conversation changed slightly to include the range of interest, opportunities, and programs focused around Rare Diseases (R.A.R.E, Every Life Foundation, Rare Disease Caucus, GrandRx, Cure the Process, etc), how the Rare Disease Community is focused on developing tools to streamline the drug development process for rare disease and the worldwide focus on RARE.
At the end of the week, I participated in my last face-to-face meeting with the Institute of Medicine Committee. I have been serving on this committee for the last year. While some of the committee members knew each other in a past life, the charge of this committee was new and quite daunting. We were charged with writing a comprehensive paper on Accelerating Rare Disease Research and Product Development in Rare Diseases and writing recommendations that are expected to result in legislation. This experience has been intimidating, amazing, and wonderful all at the same time. The committee is comprised of individuals representing a broad range of expertise –academia (clinical trial experts, epidemiology, rare disease), researchers, venture capital, drug/device executives, attorneys, and foundations. This last meeting was bittersweet. We came to the end of our investigation, reporting progress to date and making recommendations for changes that we hope will positively impact the trajectory of treatments and cures. For me, it was a incredible learning experience, to systematically go through what we now know about rare disease, what we need to know, what tools need to be developed, what processes need to be streamlined, and where resources would be useful. What was even more moving was to understand that each member of the committee had been impacted by a rare disease, that each member understood how rare disease isolates, how rare disease impacts individuals, and how we, as a country might work together to break barriers that get in the way.
Friday, May 28, 2010
Ataluren Update
As many of you know, because you participated, PTC held an open conference call yesterday to update the community about ataluren and future plans. The discussion included analysis of data from the ataluren trial and a summary of regulatory challenges. Langdon Miller (Chief Medical Officer for the trial) described PTC’s plan for regulatory interactions relating to ataluren and the effects of these interactions on potential patient access to ataluren.
And when the call was over, like many of you, I walked away from the call still frustrated, still hurting for our boys.
I understand the urgency to complete the sub-analysis and to prepare the package to establish the path forward. Like you, I worried we would again be waiting until the presentation in Naples and another call.
Time. And like you, I have watched my own two sons lose strength and felt my heart break over and over again for them and for all of you.
I reviewed this conversation in my head throughout the night and today. I wanted to have something concrete to hold onto and step-by-step I went through the call. And I made some calls.
Here is what I understand:
By the Naples meeting PTC will have completed the analysis and prepared the package for the regulatory path ahead. Keep in mind, while on the call, PTC talked about an access program and mentioned Individual IND’s. I think the risk/benefit of the individual IND is worth pursuing as each day these boys lose function. You already know, I think in increments of 5 minutes: treasuring every one of those moments and hoping to buy more. I know all of you feel the same.
This morning I spoke with PTC and asked that question in order to get some details and clarification. PTC confirmed that they are planning for individual IND’s. Planning is being done in parallel to data analysis and preparing the regulatory package. PTC is interested in understanding who/how many of the families are interested in securing an individual IND. Please contact your site coordinator and ask if they would be willing to participate in an individual IND.
I know what you are thinking, that you may have another willing physician. At the moment, PTC wants to understand:
From the FDA SITE: The sponsor is the person who takes responsibility for and initiates a clinical investigation. The sponsor may be a pharmaceutical company, a private or academic organization, or an individual. A Sponsor-Investigator is an individual who both initiates and conducts a clinical investigation and under whose immediate direction the investigational drug is being administered or dispensed. For administrative reasons, only one individual should be designated as sponsor.
I feel – PPMD feels – that it is our job to tell your stories to PTC and any other company working in Duchenne. And we will.
I have said it before – I continue to believe in the work of PTC. I believe they are committed to helping our sons and I truly credit them with being trailblazers in Duchenne treatment. I also commend them for their communication with us. Most pharmaceutical companies would remain silent in a situation like this and while we may be frustrated by the information we receive or the amount of information we have received, at least we are not listening to silence.
But we won’t sit still and we won’t sit quietly.
And when the call was over, like many of you, I walked away from the call still frustrated, still hurting for our boys.
I understand the urgency to complete the sub-analysis and to prepare the package to establish the path forward. Like you, I worried we would again be waiting until the presentation in Naples and another call.
Time. And like you, I have watched my own two sons lose strength and felt my heart break over and over again for them and for all of you.
I reviewed this conversation in my head throughout the night and today. I wanted to have something concrete to hold onto and step-by-step I went through the call. And I made some calls.
Here is what I understand:
By the Naples meeting PTC will have completed the analysis and prepared the package for the regulatory path ahead. Keep in mind, while on the call, PTC talked about an access program and mentioned Individual IND’s. I think the risk/benefit of the individual IND is worth pursuing as each day these boys lose function. You already know, I think in increments of 5 minutes: treasuring every one of those moments and hoping to buy more. I know all of you feel the same.
This morning I spoke with PTC and asked that question in order to get some details and clarification. PTC confirmed that they are planning for individual IND’s. Planning is being done in parallel to data analysis and preparing the regulatory package. PTC is interested in understanding who/how many of the families are interested in securing an individual IND. Please contact your site coordinator and ask if they would be willing to participate in an individual IND.
I know what you are thinking, that you may have another willing physician. At the moment, PTC wants to understand:
- Who is interested in an individual IND, and
- If the physician from your clinical site would be willing to act as the sponsor.
From the FDA SITE: The sponsor is the person who takes responsibility for and initiates a clinical investigation. The sponsor may be a pharmaceutical company, a private or academic organization, or an individual. A Sponsor-Investigator is an individual who both initiates and conducts a clinical investigation and under whose immediate direction the investigational drug is being administered or dispensed. For administrative reasons, only one individual should be designated as sponsor.
I feel – PPMD feels – that it is our job to tell your stories to PTC and any other company working in Duchenne. And we will.
I have said it before – I continue to believe in the work of PTC. I believe they are committed to helping our sons and I truly credit them with being trailblazers in Duchenne treatment. I also commend them for their communication with us. Most pharmaceutical companies would remain silent in a situation like this and while we may be frustrated by the information we receive or the amount of information we have received, at least we are not listening to silence.
But we won’t sit still and we won’t sit quietly.
Monday, April 19, 2010
Week in Review: 4/11-4/15
I spent the better part of the week in Washington, DC with a full agenda. On Monday, I met with Peter Saltonstall (president of NORD). One of NORD’s major interests is the FDA. You are probably familiar with our advocacy agenda, this year concentrating on several areas relevant to clinical trials – one very specifically directed toward FDA. One of our requests focused on securing additional resources for the FDA, specifically more expertise and experience on rare disease (Duchenne), communication, and collaboration with the orphan products division and efforts to harmonize interaction between EMEA (European regulatory agencies) and FDA. NORD is focused on the same issues and when voices join together with specific messages, things happen. Anne Pariser, MD is now the Associate Director of Rare Disease, a new position with FDA.
On Monday evening, I served on a NORD panel to discuss barriers facing therapies for rare diseases. I spent some time discussing barriers such as risk benefit (such as asking for definitions of risk when the condition is fatal) and discussing TIME (how minutes matter when, in progressive conditions, each minute represents cell degeneration and death). Time. Loss of function. Lost time with someone you love. And steady state. How many times have we all prayed, that Duchenne stops now. Today. Steady state, no further degeneration.
On Tuesday I met with Anne Pariser. Anne has worked for the FDA for over 10 years, working in the area of inborn errors of metabolism. She is wonderful and anxious to accelerate therapies for rare disease. We discussed exon skipping and meetings planned for Fall. And I took a left turn in the conversation. You may already be aware, NIH (NINDS/John Porter/Berch Griggs/Katie Bushby-Treat NMD) have been awarded a
grant for a multi-site steroid trial. The trial will have several arms, evaluating an intermittent regimen with daily
Deflazacort and daily Prednisone. Makes no sense to me unless, at the end of the day, should the data suggest Deflazacort has less side effects (weight gain/behavior) it would be available (and covered by insurance) for families in the US. Anne said she had no knowledge of the trial. Now she does. And John Porter is connected to Dr. Pariser. And those planning the trial are connected to Dr. Pariser and to Elizabeth McNeil (orphan products). One of the goals of this study will be to (FINALLY) have Deflazacort available and approved in the US and hopefully elsewhere. Families deserve choices…and trials must consider access to whatever they are testing. Families already have significant financial burden in Duchenne. ALL therapies must be available and ALL boys must have access without additional expense.
grant for a multi-site steroid trial. The trial will have several arms, evaluating an intermittent regimen with daily
Deflazacort and daily Prednisone. Makes no sense to me unless, at the end of the day, should the data suggest Deflazacort has less side effects (weight gain/behavior) it would be available (and covered by insurance) for families in the US. Anne said she had no knowledge of the trial. Now she does. And John Porter is connected to Dr. Pariser. And those planning the trial are connected to Dr. Pariser and to Elizabeth McNeil (orphan products). One of the goals of this study will be to (FINALLY) have Deflazacort available and approved in the US and hopefully elsewhere. Families deserve choices…and trials must consider access to whatever they are testing. Families already have significant financial burden in Duchenne. ALL therapies must be available and ALL boys must have access without additional expense.
Wednesday and Thursday I was in closed meetings with the Institute of Medicine (IOM). Our task is to produce a report (Fall, 2010) on “Accelerating Rare Disease Research and Orphan Product Development.” The report will include discussions and recommendations on discovery, drug development, FDA, the Clinical trial process, insurance, Medicare/Medicaid and devices. You might be aware of Senator Spector’s CAN legislation – $500 million for rare disease. Cross fingers and pray this legislation becomes law.
Progress!
Tuesday, April 6, 2010
Albania
During the Connect Conference last year, I was invited to speak in Albania. It is hard to say no to invitations during the Conference because the need is so clear and the impact of information so evident. So, I said yes…knowing it would be sometime in the future and maybe, depending on the circumstances, might not happen. In January, Mira contacted me reminding me of our conversation and the scheduled date, March 27. In January, the end of March seemed far away.
I met Mira some years ago. This is a story we all know well. While Mira is a neurologist, she does not see individuals with Duchenne, rather only one, her friend’s son. He was diagnosed at six. No intervention recommended. None. Therapeutic nihilism.
He started steroids at the age of 18. Mira attended our conference in Philadelphia, coming back year after year. She delivered information and advice to the family, and this young man’s quality of life improved. She learned how to buy time. At 24 years old, his echocardiogram is stable. He is on steroids, ace inihibitors, beta blockers, supplements, swims three times/week, works for his father, and enjoys spending time with his friends. For this one young man, life is good.
On March 26, I arrived in Albania. The airport was small and as I watched the luggage arrive in baggage claim, I had the sinking feeling that mine had not made the connection from Rome. With only one flight/day from Rome to Tirana, there was no chance of clean clothes anytime soon. I had been traveling for 20 hours or so and looked it! Wrinkled clothes, bad hair, and no makeup! I was scheduled to speak early Saturday AM during the Albanian Neurology Conference. Thanks to Mira’s influence, this year was focused on Duchenne. Several Coke Zero’s (could not find a Diet Coke anywhere!) later and life improved.
Mira and I went out for lunch and a short history lesson about Albania. The communists were defeated just 20 years ago. The communists’ occupation included confiscating homes, tearing down churches, persecuting religious beliefs, taking away freedom, and crushing dreams. Medical care remains under government control. Patients are able to see their doctors, but there is little access to medicines. Rare disease... well, better not to have a rare disease in Albania.
A pause. The country of Albania is beautiful. Flying in, the 60,000 ft. view is lovely. Tirana is surrounded by mountains and bordered on the West and South by the Sea. On the ground, the people are warm, friendly, and kind. But I did see something else and maybe it was best characterized by the lovely young woman that interviewed me. We talked about Duchenne and about Albania. She said, "We try but dreams of change feel impossible, a mountain too difficult to climb."
The meetings started at 8:30AM and most of the talks were in Albanian. Doctors from around the country attended the meeting as well as neighboring countries such as Kosovo. The neurologist who cares for individuals with Duchenne spoke just before me. A kind, young doctor was sitting next to me, translating phrases, though as I stared at the slides, I understood. I closed my eyes and was back in 1984. The slides on the diagnostic workup hit a nerve –clinical presentation, EMG…. EMG! It was 1984, Children’s Hospital Cincinnati. I was standing next to my beautiful son Patrick. He was 4, with his blue eyes open wide and tears falling, “Mom, make them stop” and a frustrated technician telling him to grow up. EMG means sticking needles in a nerve to measure conduction. It was horrifying then and now. In 1984, EMG was done on Duchenne. I’ll never understand why or how EMG was included in the diagnostic workup and I screamed at the tech and later the neurologist. I did not understand the rationale then and certainly not now.
But today, at this meeting in Albania, EMG was included on the slide. I thought I was tired, misread the slide. The neurologist then described their genetic testing capability, that approximately 60% of the mutations were identified. What about the rest? Recommendations for steroid use are limited to an intermittent regime. There is no registry in Albania, no access to sequencing, no thought of clinical trials. One neurologist commented “you are the first parent I have ever met.” I’m certain he meant that I was the first parent ever to speak to physicians. My talk focused around “who’s actually in charge… the doctor who sees the patient for a short time, say 2 hours/year or the patient/family who spend around 8700 hours together each year?...” As part of the Q&A, I was asked about care in the US and answered step by step: no EMG, clinical diagnosis, genetic testing (full sequencing), steroids – and on and on and on.
This was my first trip to the region and while I recall hearing sound bites of information about communist oppression in the Balkans, I did not realize the real impact. While I cannot walk in their shoes, I learned from being there, from the stories. The communist presence is still felt. The Albanian people are rebuilding, but slowly. They lack educational opportunities and infrastructure. There are remnants of communism in healthcare, doctors who deliver the ‘no hope and no help’ messages. There are remnants of communism throughout the country, in buildings and in empty spaces, where homes, churches, and businesses used to exist. There are remnants of communism in the mentality of the people, perhaps reluctant to dream that things might be different. And there are pockets of strikingly beautiful areas everywhere, storybook places, where new dreams are planted.
And, as Duchenne connects all of us, together we will fertilize and help to nourish those young plants so that boys in Albania will have opportunities and dreams.
I met Mira some years ago. This is a story we all know well. While Mira is a neurologist, she does not see individuals with Duchenne, rather only one, her friend’s son. He was diagnosed at six. No intervention recommended. None. Therapeutic nihilism.
He started steroids at the age of 18. Mira attended our conference in Philadelphia, coming back year after year. She delivered information and advice to the family, and this young man’s quality of life improved. She learned how to buy time. At 24 years old, his echocardiogram is stable. He is on steroids, ace inihibitors, beta blockers, supplements, swims three times/week, works for his father, and enjoys spending time with his friends. For this one young man, life is good.
On March 26, I arrived in Albania. The airport was small and as I watched the luggage arrive in baggage claim, I had the sinking feeling that mine had not made the connection from Rome. With only one flight/day from Rome to Tirana, there was no chance of clean clothes anytime soon. I had been traveling for 20 hours or so and looked it! Wrinkled clothes, bad hair, and no makeup! I was scheduled to speak early Saturday AM during the Albanian Neurology Conference. Thanks to Mira’s influence, this year was focused on Duchenne. Several Coke Zero’s (could not find a Diet Coke anywhere!) later and life improved.
Mira and I went out for lunch and a short history lesson about Albania. The communists were defeated just 20 years ago. The communists’ occupation included confiscating homes, tearing down churches, persecuting religious beliefs, taking away freedom, and crushing dreams. Medical care remains under government control. Patients are able to see their doctors, but there is little access to medicines. Rare disease... well, better not to have a rare disease in Albania.
A pause. The country of Albania is beautiful. Flying in, the 60,000 ft. view is lovely. Tirana is surrounded by mountains and bordered on the West and South by the Sea. On the ground, the people are warm, friendly, and kind. But I did see something else and maybe it was best characterized by the lovely young woman that interviewed me. We talked about Duchenne and about Albania. She said, "We try but dreams of change feel impossible, a mountain too difficult to climb."
The meetings started at 8:30AM and most of the talks were in Albanian. Doctors from around the country attended the meeting as well as neighboring countries such as Kosovo. The neurologist who cares for individuals with Duchenne spoke just before me. A kind, young doctor was sitting next to me, translating phrases, though as I stared at the slides, I understood. I closed my eyes and was back in 1984. The slides on the diagnostic workup hit a nerve –clinical presentation, EMG…. EMG! It was 1984, Children’s Hospital Cincinnati. I was standing next to my beautiful son Patrick. He was 4, with his blue eyes open wide and tears falling, “Mom, make them stop” and a frustrated technician telling him to grow up. EMG means sticking needles in a nerve to measure conduction. It was horrifying then and now. In 1984, EMG was done on Duchenne. I’ll never understand why or how EMG was included in the diagnostic workup and I screamed at the tech and later the neurologist. I did not understand the rationale then and certainly not now.
But today, at this meeting in Albania, EMG was included on the slide. I thought I was tired, misread the slide. The neurologist then described their genetic testing capability, that approximately 60% of the mutations were identified. What about the rest? Recommendations for steroid use are limited to an intermittent regime. There is no registry in Albania, no access to sequencing, no thought of clinical trials. One neurologist commented “you are the first parent I have ever met.” I’m certain he meant that I was the first parent ever to speak to physicians. My talk focused around “who’s actually in charge… the doctor who sees the patient for a short time, say 2 hours/year or the patient/family who spend around 8700 hours together each year?...” As part of the Q&A, I was asked about care in the US and answered step by step: no EMG, clinical diagnosis, genetic testing (full sequencing), steroids – and on and on and on.
This was my first trip to the region and while I recall hearing sound bites of information about communist oppression in the Balkans, I did not realize the real impact. While I cannot walk in their shoes, I learned from being there, from the stories. The communist presence is still felt. The Albanian people are rebuilding, but slowly. They lack educational opportunities and infrastructure. There are remnants of communism in healthcare, doctors who deliver the ‘no hope and no help’ messages. There are remnants of communism throughout the country, in buildings and in empty spaces, where homes, churches, and businesses used to exist. There are remnants of communism in the mentality of the people, perhaps reluctant to dream that things might be different. And there are pockets of strikingly beautiful areas everywhere, storybook places, where new dreams are planted.
And, as Duchenne connects all of us, together we will fertilize and help to nourish those young plants so that boys in Albania will have opportunities and dreams.
Wednesday, March 31, 2010
GSK & PTC Updates
GSK
First off, a qualifier. If you are reading this for inside information, such as the start date of the trial, the protocol, the willingness (or not) to consider compassionate use, etc., stop reading right now.
We (Sharon Hesterlee, Kimberly Galberaith, and I) met the GSK team and while all of those thoughts were on our mind, we knew that those were not the questions to ask and that we were not meeting for the purpose of asking for confidential information in an effort to leak it to the greater community. Rather we were meeting to think about how we might work together to support and accelerate trials (and hopefully treatments) for our sons.
The GSK folks we met with consisted of the people involved in scientific communications, global commercial strategy, alliance development, and public policy. We went into this meeting without an agenda. We felt a synergy the moment we met and the conversation flowed from there, covering a range of topics to include urgency, high unmet need, anticipation, and expectations. We discussed the GSK relationship with Prosensa and the capability and capacity they bring to the table. It was obvious that GSK is committed to Duchenne. It felt good to see their interest in Duchenne, their openness to new opportunities, and here’s the thing...having GSK (better known as ‘big pharma’) onboard is quite a coup to be honest. These folks know the ropes, they have experience in taking drugs through the clinical process and to market.
We spent some time talking about the individuals and families who do not fit into the current antisense compounds (rare deletions, duplications), how the community feels fragmented based on mutations, as if, for some boys, there is less hope than for others. We talked about the fragility of the community, the increased frustration and desperation as strength decreases and walking is threatened. They understood, perhaps not to the degree of parents/families watching minute by minute, but the message was heard loud and clear. We spent a good bit of time discussing the need for a regular communications plan, a website where all foundations/organizations would direct interested individuals: the one-stop shopping for accurate information and consistent messaging, so that information does not arrive in sound bites or tidbits of information from anyone, rather information we all can count on to be accurate. We learned that while this sounds easy on some level, there are loads of hoops before information is released and SEC and regulatory concerns that need to be considered, such as communication that might suggest results or promise, or anything that can be perceived as persuasive in terms of trial recruitment.
We discussed clinical sites and whether more with fewer patients is better or less with more patients might produce better data with less variability. We discussed using clinical sites with expertise and experience (and trust by the community) in Duchenne AND with clinical trial experience.
We discussed their commitment. And while it is true, none of the people we met with have a child with Duchenne, they all have a story about their interest in medicine, the soundtrack of their lives where the twists and turns of their careers brought them to this place, this world of Duchenne. And they seemed happy to be here, dedicated to making a difference and joined the ‘church’ of believers, that Duchenne can and will have treatments.
As you might imagine, we left with that same laundry list of questions in our head, but respected the fact that data would become public during the AAN meeting. We discussed protocols, asked if they would consider expanded access or compassion and the ever present “WHEN” question. No answers at the moment and all possibilities are in discussion.
GSK/Prosensa will release data from the European trial during the upcoming AAN meeting, April 12-17 i in Toronto. Exact date is April 15. Stay tuned.
PTC
Same qualifier as above. If you are looking for sub-analysis data and next steps, stop reading.
Later the same day, we met with Stuart Peltz, Langdon Miller, Theresa Nalatacchio, and Diane Goetz. Fatigue was obvious as the analysis continues. You all already know, I think the PTC folks are what my mother calls “good people.” I have known Stu Peltz for 7 years. He is committed to Duchenne. He is a fighter. With his team he is sorting the data, sifting through to see the path forward. They believe there is a path and I think this coincides with the community’s belief. It isn’t easy and the path is not crystal clear at this moment as they weight the arguments and plans for moving forward.
We discussed the fact that the community feels like the rug has been pulled out from under, that the messaging from the clinical sites varying and frustrating, that parents are worried about what happens physically and psychologically as the drug/compound is stopped. And that frustration has turned to anger and there is no place to put the anger. Stu and his colleagues understand.
I guess that’s hard to imagine from where you sit, but it was quite obvious on their faces. This was not the plan. PTC has been the pioneer, the oldest child (in a manner of speaking) trying to carve a path forward in the best way possible, with a community that has not participated in registration trials, a community that does not have rigorous natural history data, a community with high unmet medical needs, and a sense of urgency that is hard to actually put into words. An urgency that makes a parents’ blood flow feel like lava when their child falls, or stops walking, or worse.
I believe in PTC and believe that they are working very hard to develop a plan for success. We talked about access programs, about compassion, and talked about Genzyme’s program. I was surprised to learn that Genzyme’s program for expanded access involved less than 5 people. PTC has 200 +/- boys who have participated in trials to consider as they plan next steps. They are listening. But at the same time, they need to succeed, otherwise even expanded use or compassionate use would come to a stop.
Ataluren needs a path forward, so that all boys who could likely benefit, have access to that opportunity.
First off, a qualifier. If you are reading this for inside information, such as the start date of the trial, the protocol, the willingness (or not) to consider compassionate use, etc., stop reading right now.
We (Sharon Hesterlee, Kimberly Galberaith, and I) met the GSK team and while all of those thoughts were on our mind, we knew that those were not the questions to ask and that we were not meeting for the purpose of asking for confidential information in an effort to leak it to the greater community. Rather we were meeting to think about how we might work together to support and accelerate trials (and hopefully treatments) for our sons.
The GSK folks we met with consisted of the people involved in scientific communications, global commercial strategy, alliance development, and public policy. We went into this meeting without an agenda. We felt a synergy the moment we met and the conversation flowed from there, covering a range of topics to include urgency, high unmet need, anticipation, and expectations. We discussed the GSK relationship with Prosensa and the capability and capacity they bring to the table. It was obvious that GSK is committed to Duchenne. It felt good to see their interest in Duchenne, their openness to new opportunities, and here’s the thing...having GSK (better known as ‘big pharma’) onboard is quite a coup to be honest. These folks know the ropes, they have experience in taking drugs through the clinical process and to market.
We spent some time talking about the individuals and families who do not fit into the current antisense compounds (rare deletions, duplications), how the community feels fragmented based on mutations, as if, for some boys, there is less hope than for others. We talked about the fragility of the community, the increased frustration and desperation as strength decreases and walking is threatened. They understood, perhaps not to the degree of parents/families watching minute by minute, but the message was heard loud and clear. We spent a good bit of time discussing the need for a regular communications plan, a website where all foundations/organizations would direct interested individuals: the one-stop shopping for accurate information and consistent messaging, so that information does not arrive in sound bites or tidbits of information from anyone, rather information we all can count on to be accurate. We learned that while this sounds easy on some level, there are loads of hoops before information is released and SEC and regulatory concerns that need to be considered, such as communication that might suggest results or promise, or anything that can be perceived as persuasive in terms of trial recruitment.
We discussed clinical sites and whether more with fewer patients is better or less with more patients might produce better data with less variability. We discussed using clinical sites with expertise and experience (and trust by the community) in Duchenne AND with clinical trial experience.
We discussed their commitment. And while it is true, none of the people we met with have a child with Duchenne, they all have a story about their interest in medicine, the soundtrack of their lives where the twists and turns of their careers brought them to this place, this world of Duchenne. And they seemed happy to be here, dedicated to making a difference and joined the ‘church’ of believers, that Duchenne can and will have treatments.
As you might imagine, we left with that same laundry list of questions in our head, but respected the fact that data would become public during the AAN meeting. We discussed protocols, asked if they would consider expanded access or compassion and the ever present “WHEN” question. No answers at the moment and all possibilities are in discussion.
GSK/Prosensa will release data from the European trial during the upcoming AAN meeting, April 12-17 i in Toronto. Exact date is April 15. Stay tuned.
PTC
Same qualifier as above. If you are looking for sub-analysis data and next steps, stop reading.
Later the same day, we met with Stuart Peltz, Langdon Miller, Theresa Nalatacchio, and Diane Goetz. Fatigue was obvious as the analysis continues. You all already know, I think the PTC folks are what my mother calls “good people.” I have known Stu Peltz for 7 years. He is committed to Duchenne. He is a fighter. With his team he is sorting the data, sifting through to see the path forward. They believe there is a path and I think this coincides with the community’s belief. It isn’t easy and the path is not crystal clear at this moment as they weight the arguments and plans for moving forward.
We discussed the fact that the community feels like the rug has been pulled out from under, that the messaging from the clinical sites varying and frustrating, that parents are worried about what happens physically and psychologically as the drug/compound is stopped. And that frustration has turned to anger and there is no place to put the anger. Stu and his colleagues understand.
I guess that’s hard to imagine from where you sit, but it was quite obvious on their faces. This was not the plan. PTC has been the pioneer, the oldest child (in a manner of speaking) trying to carve a path forward in the best way possible, with a community that has not participated in registration trials, a community that does not have rigorous natural history data, a community with high unmet medical needs, and a sense of urgency that is hard to actually put into words. An urgency that makes a parents’ blood flow feel like lava when their child falls, or stops walking, or worse.
I believe in PTC and believe that they are working very hard to develop a plan for success. We talked about access programs, about compassion, and talked about Genzyme’s program. I was surprised to learn that Genzyme’s program for expanded access involved less than 5 people. PTC has 200 +/- boys who have participated in trials to consider as they plan next steps. They are listening. But at the same time, they need to succeed, otherwise even expanded use or compassionate use would come to a stop.
Ataluren needs a path forward, so that all boys who could likely benefit, have access to that opportunity.
Monday, March 8, 2010
Katrina Revisited
I don’t know about you but I felt last week the Duchenne community was hit with our own hurricane, similar to the 5th deadliest hurricane in US history, 2005 Katrina. I’m not from New Orleans, but have a good friend, Diane, whose home was washed way when the levee system failed and neighboring parishes flooded. The 175 mile winds took everything - house, furniture, photos, memories, life as she knew it. While nearly 2,000 people lost their lives, her family managed to survive. She was in Cincinnati at the time, desperately seeking information and connections to those she loved. I could not imagine how she felt during that time, but saw it on her face: pain, desperation, sadness.
I cannot relate to Katrina, but on Saturday I felt like I was seeing the aftermath of our own ‘hurricane.’ The wind died down and the reality hit. As a community, we were left in the aftermath, trying to makes sense of the news, trying to find some meaning, some hope.
I have been following the discussions, the criticism, the sadness . These trial results are not what we expected or wanted. We all wanted a win for Duchenne. We depended on it as if it would feel like a neon sign that this one win would lead to more, would mean the stars were lining up just right. And sometimes when we hear bad news, everything else in the world looks bleak.
I must have asked Tom how he was feeling a million times, thinking the universe must be against us. Finally he told me I was simply not allowed to ask. I went to the nursing home to see my mother and this sweet 94-year-old German Catholic woman who taught me that "life is not a rehearsal and while you may not be able to control the boulders thrown in your path, you will find a way to walk around, over or compensate for them”; this lovely woman looked at me with tears in her eyes and said that ‘they’ were giving her pills to hurt her and there was no way to reason with her. She was afraid and I could not convince her that I knew what pills she was taking, that I was in contact with the doctors, that I would keep her safe. Senile dementia. I left feeling defeated, helpless. And my daughter Michelle moved into her new flat in London (Primrose Hill, Princess Lane), the boiler failed, and she had no heat or hot water. At that moment, I wanted to fly to London and bring her home to my safe house. (If you were to meet some of my relatives, you would understand that they typically do not allow children to move far from home). I called my other daughter Jenny to make sure she was safe. I had no reason to doubt it, but it felt like the universe had changed on its axis.
The discussions on the website reflect anger and sadness. We are all grieving. Discussions related to trial design – was it the right design? Was the 6 Minute Walk Test (6MWT) the best or worst choice as an outcome measure? How do you measure benefit in a population where clinical variability (function, progression, cognition) are highly variable? Should the stratification of the trial have been more precise as in eliminating boys who could not walk a certain distance (<350m) in the 6MWT? Too many sites/wrong sites? How much dystrophin expressed? What are the individual responses? Why can’t you change course in the middle of a trial? Do something different? Why suspend all trials? What about compassion? And what next?
I find the criticism and the desire to point the finger at someone or something incredibly sad and a bit overwhelming. I understand it as I have been angry since Duchenne entered my home, my vocabulary, my every thought. But it is DUCHENNE I hate, not the people. I thought about my own life and the decisions I have made and how with additional information, I might have made different decisions. I have made good decisions, bad decisions, ‘meh’ decisions (those are not so important decisions), and have had the opportunity to revise and re-do and some of the time, rethinking and redoing has improved the original decision by leaps and bounds. Pity that we don’t have a crystal ball.
On Saturday I received a call from a mom who had been contacted by another mom, whose son was not in the trial. The description of the call was sad – pointing the finger, criticizing people, recommending litigation. I was at first angry and then sadness fell on me like a wet blanket.
After that unsettling call, I drove to the Dorothy Lane Market in Dayton. I bought 3 way too expensive cookies (Laura’s large sugar cookies @ $3.00 per). If I was in New York, I would have gone to the Magnolia Bakery for cupcakes, but I was in Middletown, so the choices were limited. I ate all 3! I think it took less than 5 minutes to consume all of them, what may be upwards of a total of 3000 calories. While they were going down, I loved it. I thought it was perhaps the best investment ever. Then I went to my favorite shop in Hyde Park and tried on pants for summer. I could not button them at the waist and the way they looked in the mirror did not fit with the image I had in my head. So I left. In retrospect, I should not have eaten the cookies, should not have stopped running after freezing my bottom off in Florida in January, and should not have York Peppermint Patties sitting on my desk. Bad decisions and if I could get a do-over, I might make other choices.
Divorce/partners –another example. You marry your partner because it looks like a good decision at the time. Over time you learn more, life throws in a few boulders, and you find you need to make a different decision. And you do and the second time around it is sometimes better. Different factors, new knowledge, experience, wisdom. Your primary endpoint changed? Secondary endpoints different?
All this is trivial in light of a clinical trial that may mean the difference between maintaining/improving function or not and extending the length of life. But in some strange way, there are similarities. Decisions are made based on knowledge at the time. Trials are developed with advice and expertise from a range of individuals to include parents/patients – experts ( specific disease process, drug development, regulatory, business model, etc) and with all of that in mind, trials are conducted and data analyzed. The data informs and based on recommendations (in this case) the trial is suspended. Keep in mind, SUSPENDED is not ENDED. SUSPENDED to regroup, rethink, analyze, and clear the path forward.
I hear the phrase "compassionate use", but the case (based on current data primary /secondary outcomes) is not there.
So, we have to wait. Wait for sub-analysis. Wait for the plan. And once the path is developed, we will do whatever it takes to move toward success. Like you, I have heard the anecdotal stories –both positive and negative. I remain a believer –that Duchenne will have treatments and in the near future, that suppression of premature stops is a promising strategy. That exon skipping, utrophin upregulation, myostatin inhibition,
increasing nNOS – are all potentially promising.
increasing nNOS – are all potentially promising.
But I am not ready to throw arrows at anyone or anything...except Duchenne.
We are all reeling in the aftermath of our first (and hopefully only) hurricane. We have all fallen apart in our own ways. Let’sgather, like my friend, go back and sift through what we have learned and moveforward together. Stu Peltz and everyone at PTC are committed to our sons. There is a way forward and we will find it.
P.S. Diane sorted through the rubble and found a picture of her dad in perfect condition.
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