For Immediate Release: Feb. 14, 2014 Media Inquiries: Andrea Fischer, 301-796-0393, andrea.fischer@fda.hhs.gov Consumer Inquiries: 888-INFO-FDA
FDA approves Vimizim to treat rare congenital enzyme disorder First drug to receive Rare Pediatric Disease Priority Review Voucher
The U.S. Food and Drug Administration today approved Vimizim (elosulfase alfa), the first FDA-approved treatment for Mucopolysaccharidosis Type IVA (Morquio A syndrome). Morquio A syndrome is a rare, autosomal recessive lysosomal storage disease caused by a deficiency in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Vimizim is intended to replace the missing GALNS enzyme involved in an important metabolic pathway. Absence of this enzyme leads to problems with bone development, growth and mobility. There are approximately 800 patients with Morquio A syndrome in the United States.
Vimizim was granted priority review. An FDA priority review provides for an expedited review of drugs for serious diseases or conditions that may offer major advances in treatment. Vimizim is also the first drug to receive the Rare Pediatric Disease Priority Review Voucher – a provision that aims to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.
“This approval and rare pediatric disease priority review voucher underscores the agency’s commitment to making treatments available to patients with rare diseases,” said Andrew E. Mulberg, M.D., deputy director, Division of Gastroenterology and Inborn Errors Products in the FDA’s Center for Drug Evaluation and Research (CDER). “Prior to today’s approval, patients with this rare disease have had no approved drug treatment options.”
The safety and effectiveness of Vimizim were established in a clinical trial involving 176 participants with Morquio A syndrome, ranging in age from 5 to 57 years. Participants treated with Vimizim showed greater improvement in a 6-minute walk test than participants treated with placebo. On average, patients treated with Vimizim in the trial walked 22.5 meters farther in 6 minutes compared to the patients who received placebo.
The most common side effects in patients treated with Vimizim during clinical trials included fever, vomiting, headache, nausea, abdominal pain, chills and fatigue. The safety and effectiveness of Vimizim have not been established in pediatric patients less than 5 years of age. Vimizim is being approved with a boxed warning to include the risk of anaphylaxis. During clinical trials, life-threatening anaphylactic reactions occurred in some patients during Vimizim infusions.
Vimizim is marketed by Novato, Calif.-based BioMarin Pharmaceutical Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
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FDA Approves Vimizim for Treatment of MPS IVA February 14th, 2014mcfadyena
I thought I would take a moment to update you on our latest attempt, our latest plea, to Shire Pharmaceuticals to open communication and connect with us about Jack Fowler, Expanded Access, and doing what is right for the Hunter Community as a whole.
Yesterday evening, I sent Shire CEO Flemming Ornskov and Head of R and D Phil Vickers an invitation to participate in a teleconference with Jack’s physician (and Internationally renowned MPS expert) Dr. Barbara Burton, and with Dr. Emil Kakkis, an expert in rare diseases who has a wealth of experience in the pharmaceutical world and with expanded access requests to save children’s lives. The purpose of the call was to ensure that all parties are on the same page moving forward, with the hope that a collaborative discussion can take place to best meet the needs of everyone involved.
I have not had a response from Shire, though I remain hopeful that they will agree to participate. At some point, someone at that company needs to look at this situation with a different lens. At some point, someone at Shire will have to look back at their company credo and work to “Be As Brave As The People” they treat. I’m hoping that some point is soon.
I’ll keep you updated as things progress. In the meantime, I’ve been busy speaking with numerous media outlets and scheduling in radio appearances. I can confirm that Jamie and Jason Fowler, Jack’s parents, and The Isaac Foundation will appear on a Boston Call-In Show in late February, from 9 – 10 pm. This show is carried over 38 states, so chances are we’ll be on the radio somewhere close to you.
We know that our case to #SaveJack is solid. We have everything in place to save this little boy’s life. We only need Shire to sponsor our effort, something we all know they should do.
Just a post to congratulate Isaac’s longtime pal, John Mayer, for being asked to perform at the Beatles Tribute that aired on television last night. Being asked to be a part of recognizing an iconic band like The Beatles isn’t small potatoes, and we couldn’t think of a better person to hit the stage in tribute.
Oh – it was nice to see the strap the boys had made for John as well. It looks great, and the boys are always so happy to see him using it. It was made and given out of love, and we’re thrilled it gets a bit of use.
Take Care!
A.
Congrats, John Mayer. February 10th, 2014mcfadyena
I’m excited to announce that The Isaac Foundation will be working with families throughout Canada to help ensure provincial funding for Enzyme Replacement Therapy (ERT) for MPS IVA patients is forthcoming once the treatment gets approval from Health Canada.
Morquio Syndrome is a rare disease that is part of the MPS umbrella of lysosomal storage disorders. The disease affects major organ systems in the body and leads to devastating symptoms for sufferers. These symptoms included bone and joint disease, heart and airway disease, a shortened stature, and premature death.
We have been fortunate to have had success advocating for families seeking support and treatment options for other forms of MPS in numerous provinces over the past 8 years. Currently, there are no treatment options for sufferers of MPS IVA. However, recent clinical trials for Biomarin’s Vimizim have produced very promising results, and Health Canada is expected to approve the treatment for use in Canada in the very near future – most likely before the summer of 2014. A decision by the FDA in the United States is imminent, and an approval in the US could mean that patients can access the treatment via the Federal Government’s Special Access Program. However, approval through the SAP is always contingent on provincial funding being made available.
We are excited to help advocate with families as they seek treatment options for themselves or their affected children, and will work with the same passion and resolve that we have given all of our other advocacy efforts.
If you or your family is interested in working with The Isaac Foundation to help bring ERT to your province for yourself or your children, please don’t hesitate to contact Andrew McFadyen at HERE or via telephone at 613.328.9136.
For more information about Morquio A Syndrome please click HERE.
Morquio A Syndrome (MPS IVA) Advocacy February 9th, 2014mcfadyena
Hi Everyone,
Jack Fowler’s case was presented in the Boston Globe today. And while it’s nice to get some exposure, I truly feel the editor at the Globe should be held accountable for the biased and single-sided view the article portrayed.
Nowhere in the article was the FDA’s position put forward – a position we have been open and transparent about presenting since day 1. That position is simple – access to investigational medicines outside of the clinical trial setting have NO BEARING on clinical trial results. In fact, there are cases where expanded use have helped to speed up the process. Indeed, the FDA guidelines say the following:
“There are examples in which FDA has made use of adverse events information from expanded access use in the safety assessment of a drug. There are a small number of cases in which an important adverse event was first identified during expanded access use and those adverse events were in clouded in product labelling. This is not a negative from a public health perspective – the sooner important adverse events are identified the better. Even from the sponsor’s viewpoint, early discovery of a rare adverse event is, on the whole, a benefit. Although adverse events first identified during expanded use of a certain drugs have been included in the drugs’ approval product labelling, we are unaware of any cases in which adverse event information obtained from expanded access use has resulted in denial of approval for a product.”
As I have previously noted, the FDA has been in contact with The Isaac Foundation regarding expanded access, and I have assurances that any adverse events that happen outside of the clinical trial setting will not hinder the clinical trial for any reason. Why the Boston Globe editor did not see fit to ensure that information was presented is beyond me, is unfortunate, and leaves an incomplete picture of the story as a whole.
In addition, no quotes were sought from families who have children currently participating in the trial. The trial is currently in Phase II/III and has lasted over 4 years. Families are reporting incredible results in their children – their lives have been saved. The treatment works, and the reversal of devastating symptoms these children have been experience is proof positive. Moreover, the treatment is safe! Over 4 years of clinical trial has seen NO ADVERSE EVENTS REPORTED. None. Zero. A few words from families who have experience dealing with this treatment would have shed light on the trial, the effectiveness of the treatment, and the safety of administering that treatment to our kids.
Finally, with all due respect to Dr. Muenzer, I have to object to his comment that “compassionate use will destroy a trial.” That statement flies in the face of all evidence the FDA has provided us, and flies in the face of the entire purpose of compassionate use for our kids. Expanded use guidelines were clarified by the FDA a few short years ago, and they were clarified so that physicians and pharmaceutical companies alike could fully understand that compassionate use does not affect trials. Their guidelines ensure that expanded access is provided as a treatment option for patients, not a data collection option for principal investigators or pharmaceutical companies. In short – any expanded use will not impact the trial. Not by any stretch. And to further this point, I emailed Janet Woodcock at the FDA for a direct statement on the matter. She promptly replied and said “…in our collective knowledge here at CDER, adverse events occurring during the development program have not delayed the programs. In one case, we know the drug development was actually accelerated.” One would have expected this information would be available to anyone who asked, including Shire Pharmaceuticals.
It is beyond me why the Boston Globe would neglect to present these viewpoints in their story. Journalism is supposed to present an objective viewpoint on a trending topic. It’s purview is to educate the public and allow for open discussion. For that discussion to take place – for any fair and open discussion to take place – all the viewpoints need to be laid out. Sadly, important information was precluded from the story, and I hope this entry helps clarify the matter once again.
Finally – Phil Vickers – never in this world would it be “ethically wrong” to try to save a child’s life. EVER.
On another note, I emailed Shire CEO Flemming Ornskov yesterday to ask, once again, for a collaborative solution to this matter. I am hopeful that Flemming and his team will agree to sit down directly with the FDA, Dr. Muenzer, and Dr. Burton to work through this matter, set a proper policy and guidelines for access to this investigational drug, and work to do what is best for our children. ALL of our children.
With thanks for your continued support,
The Isaac Foundation
Boston Globe – A Few Notes January 31st, 2014mcfadyena
Last night on NBC news, Shire Pharmaceuticals released a statement for the media (no personal interviews, sadly). Our response to their statement is included below.
Once again, I’m calling on Shire to publicly address our case, point by point, with their rationale for not supporting expanded access use for Jack Fowler. I’m happy to present the document publicly, and I call on Flemming Ornskov to be open, transparent, and honest with the Fowler family and the public, and provide the reasons that Shire cannot live up to their public motto by “Being Brave” to #SaveJack.
Shire’s statement reads:
We remain deeply sympathetic to Jack Fowler and his family. Patients have been, and will always be, at the heart of what we do, and have driven our desire to research potential new therapies for more than 20 years. Guidance from regulatory agencies is that expanded access to investigational medicines and devices outside of a clinical study setting should be based on the existence of compelling evidence of efficacy, or the drug’s benefit, and safety. Efficacy is typically studied in later stage trials; these data are not yet available for our investigational treatment as we have only just initiated our Phase II/III study. Shire does support, and has provided, expanded access at the appropriate stage in the development process-when clinically validated efficacy and safety information is available. We remain focused on completing our Phase II/III trial with the hope of making our investigational treatment available to as many Hunter syndrome patients as possible, as quickly as possible.
1. “Patients have been, and will always be, at the heart of what we do…”
Flemming Ornskov specifically said to the Fowler family, and I was present to witness this statement: “We don’t deal with patients. We don’t deal with families. We are in the business of developing products.”
2. ” Guidance from regulatory agencies is that expanded access to investigational medicines and devices outside of a clinical study setting should be based on the existence of compelling evidence of efficacy…”
Richard Klein, a member of the Office of Special Health Issues at the FDA (the regulatory body authority that guides expanded access protocol) has stated a few things regarding efficacy (source information at bottom):
“Confidence of safety is more important than efficacy.”
With regards to safety confidence, “for a patient with an immediate life-threatening condition, evidentiary burden is low.”
“Efficacy (and safety) of early phase investigational drugs not proven – and sometimes not known; however, might be given in hope of direct benefit to patient.”
3. “Shire does support, and has provided, expanded access at the appropriate stage in the development process-when clinically validated efficacy and safety information is available.”
Shire did not have a compassionate (or expanded use) policy in place when we approached them about Jack Fowler. I have the transcript of our teleconference where we questioned them on this fact, and they agreed that there should be something in place but that there was not. While they may have allowed this type of request in the past, they have had not set criteria to allow expanded access for patients until January of 2014, long after we approached them to #SaveJack. Incidentally, those criteria are riddled with errors, and I will post our response to that policy soon.
4. “We remain focused on completing our Phase II/III trial…”
Expanded Access to an investigation drug outside the clinical trial setting can HELP with clinical trials and, in some cases, speed up approval of a drug. As well, any adverse affects that transpire while a patient is receiving Expanded Access to a medication DOES NOT IMPACT THE CLINICAL TRIAL in the slightest. See below, direct from the FDA:
In an email to The Isaac Foundation, Janet Woodcock from the FDA stated, “…in our collective knowledge here at CDER, adverse events occurring during the development program have not delayed the programs. In one case, we know the drug development was actually accelerated.”
The FDA has made a very clear statement on this matter, and included this information in their report on Expanded Access. This report states: “Although adverse events first identified during expanded access use of certain drugs have been included in the drugs’ approved product labeling, we are unaware of any cases in which adverse event information obtained from expanded access use has resulted in denial of approval for a product.”
Former FDA Director Dr. Lester Crawford stated “The FDA, categorically, does not attach special significance to adverse events reported from such expanded access program as (one critic) has tried to join. We recognize that these programs involve less-controlled use of new drugs, and we assess the reported data accordingly. The development of a new medication is not slowed by side effects occurring outside clinical trials.”
Source from Richard Klein: http://www.fda.gov/downloads/ForIndustry/DevelopingProductsforRareDiseasesConditions/OOPDNewsArchive/UCM294794.pdf
Shire has released there guidelines for compassionate use (or expanded use) of their products. They didn’t have any criteria before we approached them, which continues to astound me. Regardless, their criteria is riddled with issues and inaccuracies, and I’ll post our response to it tomorrow.
In the meantime, the info graphic included below is a quote from Shire’s CEO Flemming Ornskov. Jamie Fowler, Jack’s mom, posted it on her page today, and it’s quite telling.
The letter below is posted on Deb Purcell’s blog site over at treypurcell.com. Deb is the director of our MPS II Fund, is a passionate advocate for children suffering from MPS, has been responsible for bringing so much awareness to the disease throughout Canada, and is one of the kindest and most caring people I have ever met.
Deb’s son Trey has MPS II and is currently enrolled in Shire’s clinical trial. Her letter below was hand-delivered to Flemming Ornskov by myself and the Fowler Family during our now infamous 30 second meeting with the CEO.
Sadly, I have a hard time believing that he read it. And I have a hard time believing he took the huge binders with over 32,000 signatures and comments from people around the globe supporting Jack. Or the other letters from parents who have children currently enrolled in the trial. And most sad of all, I expect he didn’t look or read the note that Jack’s mom left him.
Regardless, the message is poinient and is beautifully written. And because our site has been visited an unbelievable amount of times throughout this campaign, I’m including it below for you to read, comment, and share.
Oh – and Shire has been spending the bulk of their day visiting our site and reading your comments and posts. Perhaps Flemming will take a moment to read the thoughts below while he’s here.
Thanks, as always, for your love, care, and support.
Before I get on with the letter that Jamie and Jason Fowler hand delivered to Flemming Ornskov at their brief meeting in Chicago last Saturday, January 18 (more can be read at Jack’s new website: http://www.savejack.ca/), I am bursting with hopeful news. Due to new and close connections our MPS II community has developed with the FDA, this past week, our #SaveJack team connected directly with the FDA on one very important point. If an adverse event happened to Jack, would or could the FDA shut down the trial? This is a quote directly from the FDA this week:
‘As far as I know, and in our collective knowledge here at CDER, adverse events occurring during the development program have not delayed the programs. In one case, we know the drug development was actually accelerated.’
Former FDA Commissioner Dr. Lester Crawford stated:
“The FDA, categorically, does not attach special significance to adverse events reported from such expanded access program as (one critic) has tried to join. We recognize that these programs involve less-controlled use of new drugs, and we assess the reported data accordingly. The development of a new medication is not slowed by side effects occurring outside clinical trials.”
In my eyes, this has been the only question holding us back. I can see from Shire’s perspective why they would not approve a drug for a child if it could threaten their clinical trial and shut down treatment for many other children (not including the financial burden they must look at). However, with the above answer straight from the horses mouth, there is no good reason not to submit an application to the FDA for Jack Fowler to receive Intrathecal Elaprase.
It will not harm their trial. A doctor and institution are ready. The finances are in place if there are any issues with funding. We just need Shire to say yes. With this new news, I am so so so hopeful that there is no longer anything holding Shire back from saving Jack’s life.
Please please please Flemming Ornskov and Phil Vickers, the decision has been made so easy for you!! Just say yes! And finally, here’s the letter:
Dear. Dr. Ornskov,
My name is Deb Purcell and I am the mother of a boy, Trey, who lives with MPS II. The long version of our journey is on our website at www.treypurcell.com. The short(er) version, I will share with you here.
Trey was diagnosed unexpectedly at 23 months of age on February 14, 2006. That diagnosis uprooted our lives. It changed everything about what it means to be a parent, what it means to be alive. It took my husband and I at least a year to adjust to what it meant to be parents of a child with MPS II. Most of our days were filled with tears and the only reasons we could find to live were our two children at the time, Trey and his 3-month old brother Avery.
One year after diagnosis, after a huge battle with our government to access the drug, Trey began IV Elaprase. With Elaprase giving us hope, life improved. However, as you know, 2/3 of kids with Hunter’s are cognitively affected. Beginning when Trey was two, every six months we traveled to North Carolina to have Trey’s IQ tested. With each test, we were told that the chances of Trey’s brain being affected were reduced. When Trey first tested for the Intrathecal trial at the age of five in 2009, Dr. Muenzer told us Trey’s brain would be okay. His IQ was stable and Trey was beyond the age at which his IQ would decline. When Trey was six, I asked Dr. Muenzer to test Trey one last time, to be sure. It was then we were told Trey’s brain was affected and Trey would be screened for the trial.
I cannot explain to you what it is like to live for four and a half years, wondering if my son would live or die. Because that is the difference between the severe and attenuated form of Hunter Syndrome to a parent. Attenuated means college, jobs, traveling, LIFE. Possibility. Severe means g-tubes, seizures, wheelchairs, safe rooms, vegetative state, and DEATH.
For four and a half years, every moment of my life was taken up by fear. If Trey had a toilet accident, if he hit his brother, if he forgot a word, if he put his shirt or pants or shoes on backwards, if he had a tantrum, if he didn’t finish a puzzle or scribbled on paper instead of drawing, if he choked on food, if he woke in the night, I was seized by terror and the possibility that Trey’s brain was affected. Even when Trey did great, when he learned a new word, when he shared, when he learned to cut with a knife or ride a bike or put his hearing aids in, I wondered if that meant his brain was okay. For four and a half years, I lived with indescribable fear.
When we learned Trey’s brain was affected, I had the second biggest collapse of my life, the first being upon diagnosis. When I got back up after that, I had something to fight for. The Intrathecal trial.
I planned how often to call and email Dr. Muenzer so that he would know we want Trey in the trial and are dedicated and not giving up, but not so much that I would put him off. We stopped turning on any movies or TV and hired daily tutors to keep Trey’s cognition high enough long enough so he would not drop below inclusion criteria. I interviewed doctors about symptoms of hydrocephalus so I could have some indication of whether or not Trey’s intracranial pressure (ICP) would exclude him. We did anything and everything we could- I could tell you more in person- to ensure Trey would qualify for the trial.
That qualifying trip to UNC was the hardest time of my life. There was a drug that would save my son’s life, and an arbitrary number would tell us whether or not he would get it. Waiting four hours while Trey was under general anesthetic for the qualifying tests is indescribable. I have never been so close to a panic attack. For the first two hours I distracted myself with reading and practicing yoga. As we got closer to the time when Dr. Muenzer would walk in that door and give us the news, I could only sit and stare in front of me. I could not talk to my mom or husband. Every time the waiting room door opened, my stomach jumped and my heart dropped. I began to feel nauseous and sweaty and shaky and after an hour and a half of this, I thought I was going to throw up, pass out or explode (I’m not exaggerating). When Dr. Muenzer walked in and told us Trey qualified, I collapsed with relief. Trey got to live. Trey would live. I couldn’t believe it. It took me months to understand what that really meant. Trey gets to live.
Life since Trey qualified for the IT trial has changed completely. Instead of a life of fear and loss and sadness, our family is LIVING. Really living. I don’t have to wonder what skill or word Trey will lose today or push away the thought of when he will die and what song I will play at his funeral.
When Trey first started receiving IT drug, I recorded every new thing he did. This was easy to notice because Trey had stopped making big gains. He lost 25 IQ points between August 2010 when his IQ qualified him for the trial and 14 months later when he got his first dose of IT drug in October of 2011. At that point Trey was down to one-syllabyl words and 3-4 word sentences. His proprioceptive and vestibular needs led him to hit and bang anything he could get his hands on and spank any bum within his reach. His younger siblings were not safe in a room alone with him.
Now? You really need to speak with my family and those who worked with him before and after. They will cry. EVERY LAST ONE OF THEM. There have been so many changes in Trey as a result of this IT drug, I could wrote a thesis on it, but here are a few:
I can’t even count how many words are in Trey’s sentences. His language has grown so incredibly that he uses complete sentences (he used to skip small words like ‘it’ ‘as’ ‘the’), joins sentences with the word because (never did he do that before) and uses descriptive language. Trey’s speech therapist noted that before IT drug, when she tried to play a simple game with him, he would grab pieces because he couldn’t wait and throw the game when he was done because he was frustrated and didn’t know how to say he was done. About six months ago Trey threw the game and when she asked why, he said ‘Because I am done with the game and I wanted to throw the game so the pieces would go over your head.’ More recently, Trey told her he didn’t want to play so they stopped, and about two months ago, she pushed Trey even farther, telling him she wasn’t done playing so he had to wait, so he sat and waited. A month ago he kept playing until the game was over, even though he was done.
It’s small details like these that are noticeable and some I don’t even notice right away. It was random one day that I suddenly realized Trey no longer has a need to drum and hit, that he no longer smacks people’s bums.
He began to hug us. Before the trial, I could tell Trey wanted to hug, but he would lean in and back right out again. He couldn’t hug. Now we hug for hours, which as a mom told her child was going to die, is by far the best perk.
Trey is learning to swim. He is learning his letter sounds and learning to read. I never thought he would. Trey now understands one-to-one correlation with numbers and is learning to add and subtract. No matter how many times I tried, he never made this connection with numbers before.
Our family is learning ASL and for the first time Trey has the attention to sit for an hour lesson and actually attempts to form signs with his hands.
The biggest change is quality of life. Trey can be alone with his siblings, he understands not to touch sharp knives or touch hot stoves. I can tell him to go to bed and he will. For the first time, Trey is beginning to understand and make connections. When I was trying to figure out if Trey’s brain was affected or not, Melissa Hogan described ‘passing conversations’ to me and it became clear as day. When you talk to a child who is cognitively affected, it’s like you’re two cars on a highway passing each other. The connection is missed. Trey was just like that. Every day now I see new connections being made in Trey’s brain. I feel like I can see the IT Idursulfase clearing new pathways in his brain. It is so so very awesome. Trey has a progressive disease that is no longer progressive and is actually reversing itself. I keep wondering how I got so lucky and if this really is for real.
Jamie could have been me and I could have been her. Jack could have qualified for the IT trial and Trey could have been excluded. It was the flip of a coin. Chance. What would I want her to do for me if I were in her shoes? How hard would I need her to fight for my son’s life? These are questions I ask myself.
I will fight for Jack and I will fight for Trey because they are both my boys. This means fighting until Jack gets access to drug because as a parent, it is incomprehensible to me that anyone thinks another parent could give up on their child’s life. It also means fighting to get this drug approved if anyone gets in the way. If there is one thing MPS parents learn how to do better than anything else, it is to fight. We have been fighting systems, institutions, governments, schools, hospitals, insurance and pharmaceutical companies, and injustice since the day our children were diagnosed.
What would I do to get this drug approved? ANYTHING. What would you do to keep your child alive? ANYTHING. This drug has saved Trey’s life. I would do anything to get this drug approved because it is the only thing keeping Trey alive. This is not even a mild exaggeration. That some ponder its efficacy is shocking. It makes me realize that those people have no connection to families with Hunter Syndrome. This drug is a miracle.
Sincerely,
Deb Purcell
An Open Letter To Flemming Ornskov – A Passionate and Poignant Message January 28th, 2014mcfadyena
FDA NEWS RELEASE
