What I said to Congress today…
Posted by christinemcsherry on February 7, 2014
“Good morning, ladies and gentlemen. My name is Christine McSherry and my beautiful son, Jett, has eyes that are the color of the morning sky. I remember when my son first smiled at me. I remember his first words. I remember when he first grabbed my hands in his tiny ones and squeezed them. When my beautiful son was 5, his doctor told me he had Duchenne’s Muscular Dystrophy. I didn’t know anything about this disease. I learned quickly. He, like many other boys before him, would slowly waste away, his muscles being eaten away by a genetic defect. All of these boys would die. There was no cure, and all we could do was wait. When my beautiful son was 7, he began to slow down, he could not run as quickly. He didn’t know why he was slower than his friends, and we could do nothing. When he was 8, he began to fall down. At 9, he needed a scooter to get around. As the years passed, my beautiful son fell more and more. When Jett was 14, he fell hard in the shower and he told me that he couldn’t take it anymore. He asked me why this happened to him, did he do something wrong, did we? My beautiful son lives in a wheelchair now. He can no longer feed himself. He can barely use his hands at all anymore. He asked me the other day, “mom, can you hug me, because I can’t hug you anymore.”
My beautiful son was born on October 12, 1995. He likes a girl named Courtney. He dreams of being a good father one day, because he thinks that is the very best thing a man can be. But he thinks he will die in a few years, or maybe less. He said to me the other day that he can’t believe in God, because God would not do this to him. So he no longer prays…
But I pray. I pray every night, as I lay awake and stare into the darkness. I don’t sleep anymore. I pray that I am doing everything I can to save my son’s life. I pray that I can save him. I pray he will get a medication that may save him. I pray that I will watch
Sarepta Therapeutics Inc : Patent Application Titled "Splice-Region Antisense Composition and Method" Published Online
02/26/2014 | 02:01pm US/Eastern
By a News Reporter-Staff News Editor at AIDS Weekly -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by the inventors Iversen, Patrick L. (Corvallis, OR); Hudziak, Robert (Blodgett, OR), filed on April 9, 2013, was made available online on February 20, 2014 (see also Sarepta Therapeutics, Inc.).
The assignee for this patent application is Sarepta Therapeutics, Inc.
Reporters obtained the following quote from the background information supplied by the inventors: "Inhibition of protein expression by antisense targeting of DNA or RNA coding for the protein has been the subject of extensive study. Many reported procedures have employed phosphorothioate-linked oligonucleotides, which are charged, nuclease-resistant analogs of native DNA. The antisense mechanism involved is based on the activation of RNase, which cleaves the target nucleic acid to which the oligomer is bound. While these compounds have shown high activity, they also tend to show high levels of side effects, i.e. by cleavage of non-target RNA or by non-antisense mechanisms, such as nonspecific binding to proteins.
"Another class of antisense oligomers, termed RNase-inactive, do not promote cleavage of bound RNA and are believed to act by sterically blocking the molecular machinery from transcribing, processing, or translating the target sequence. While these compounds tend to produce fewer side reactions, such as nonselective cleavage, than phosphorothioate oligomers, it has generally been necessary to target specific regions of RNA, such as the AUG start codon, for successful inhibition.
"More recently, targeting of the splice acceptor junction of nuclear (unspliced) RNA by RNase-inactive oligomers has been reported. Kole and Dominski (U.S. Pat. No. 5,665,593) reported suppression of missplicing of .beta.-globin RNA, in order to combat variants of .beta.-thalassemia which result from such aberrant splicing. In this case, the aberrant splice junction was targeted, to direct splicing back to the normal site. R V Giles et al., Antisense & Nucleic Acid Drug Dev. 9:213-220 (1999), targeted a splice junction to induce missplicing of c-myc mRNA. In each of these cases, the region targeted is still somewhat restricted, in that the antisense oligomer spans the intron/exon splice junction of the pre-mRNA. Due to the advantages accorded by the use of uncharged, RNase-inactive oligonucleotides, a demonstration of further flexibility in targeting would be quite useful."
In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventors' summary information for this patent application: "In one aspect, the invention provides an antisense compound, and a corresponding method of inhibiting normal splicing of preprocessed RNA in a eukaryotic cell, by contacting the cell with such an antisense compound. The compound is characterized by:
"(a1): an uncharged morpholino backbone;
"(a2): a base-sequence length of between 12 and 25 nucleotide bases; and
"(a3): a base sequence that is complementary to a target region of a selected preprocessed mRNA coding for a selected protein, where the 5' end of the target region is 1-25 bases downstream of a normal splice acceptor site in the preprocessed mRNA,
"and having the properties that:
"(b1): the compound is taken up by eukaryotic cells;
"(b2): the compound hybridizes to the target region of preprocessed mRNA in such cells, and
"(b3): the compound so hybridized to the target pre-mRNA prevents splicing at the normal acceptor splice site, such that the splice mechanism proceeds to a downstream splice acceptor site in the preprocessed mRNA, producing a splice variant processed mRNA with a truncated coding sequence.
"In more specific embodiments, the 5' end of the target region is 2-20 bases, or 2-15 bases, downstream of the normal splice acceptor site. The length of the targeting compound is preferably about 15 to 20 nucleotide bases.
"In one embodiment, the compound has intersubunit linkages selected from the group consisting of the structures presented in FIGS. 2AA-2EE. In preferred embodiments, the linkages are selected from a phosphorodiamidate linkage as represented at FIG. 2B-B, where X=NH.sub.2, NHR, or NRR', Y=O, and Z=O, and an alternate phosphorodiamidate linkage as represented at FIG. 2B-B, where X=OR, Y=NH or NR, and Z=O. R and R' are groups which do not interfere with target binding. Preferably, R and R' are independently selected from alkyl and polyalkyleneoxy (e.g. PEG; (CH.sub.2CH.sub.2O).sub.n), or a combination thereof. The alkyl/polyalkyleneoxy chain may be substituted, preferably at the distal terminus, by a group selected from hydroxy, alkoxy, amino, alkylamino, thiol, alkanethiol, halogen, oxo, carboxylic acid, carboxylic ester, and inorganic ester (e.g. phosphate or sulfonate). Preferably, the chain (independent of substituents) is from 1 to 12 atoms long, and more preferably is from 1 to 6 atoms long. In selected embodiments, R and R' are independently methyl or ethyl. In one embodiment, X=N(CH.sub.3).sub.2, Y=O, and Z=O.
"NRR' may also represent a nitrogen heterocycle having 5-7 ring atoms selected from nitrogen, carbon, oxygen, and sulfur, and having at least as many carbon ring atoms as non-carbon ring atoms. Examples include morpholine, pyrrolidine, piperidine, pyridine, pyrimidine, pyrazine, triazine, triazole, pyrazole, pyrrole, isopyrrole, imidazole, oxazole, imidazole, isoxazole, and the like.
"When the downstream splice acceptor site is a whole multiple of three bases downstream of the normal splice acceptor site, the splice variant mRNA has a coding sequence in frame with that of the processed mRNA when it is normally spliced.
"The protein is preferably selected from the group consisting of myc, myb, rel, fos, jun, abl, bcl, p53, an integrin, a cathedrin, a telomerase, hCG, a receptor protein, a cytokine, a kinase, HIV rev, human papilloma virus, and human parvovirus B 19. In selected embodiments, the protein is selected from myc, myb, abl, p53, hCG-.beta. subunit, androgen receptor protein, and HIV-1 rev.
"In further selected embodiments, the selected protein has multiple distinct binding regions, as in most transcription factors, and the truncated coding sequence codes for a variant protein in which one such binding region is disabled. Preferably, the variant protein is a dominant negative protein. One example is human c-myc, where the variant protein is an N-terminal truncated c-myc. In this embodiment, the antisense compound employed has a base sequence selected from the group consisting of SEQ ID NOs: 16 through 32 herein. The variant protein may also be a C-terminal altered c-myc, in which case the antisense compound employed can be an 18- to 20-mer having a base sequence which is a contiguous sequence selected from SEQ ID NO: 34; e.g. SEQ ID NO: 33.
"In additional exemplary embodiments, the selected protein and the corresponding antisense base sequence(s) targeting its pre-mRNA are selected from the group consisting of:
Posted by christinemcsherry on February 10, 2014
You helped, and we owe you an update…so here it is!! Thanks to your outreach efforts, Friday’s congressional briefing was packed. More than 100 people jammed the room to hear about Duchenne and the urgent need to use accelerated pathways for approving new treatments.
Click here to watch a 5-minute highlights video.
What’s next? We are following up with all of the congressional offices who attended. Our “ask” is that FDA accept and promptly review a New Drug Application for Eteplirsen, a promising new treatment that can help 13% of people with Duchenne. The quicker this drug moves through the regulatory process, the quicker similar drugs will be developed. One of those compounds waiting on the shelf can help Charley. We need to get Eteplirsen approved so the children who can benefit from this first drug get treated without further delay. And so the follow-on drugs can move forward. Not years down the road. This year, now, 2014.
For all you news junkies out there, here are the full remarks from the four parents who spoke at the briefing:
Christine McSherry, Jett’s mom
Jett Good morning, ladies and gentlemen. My name is Christine McSherry and my beautiful son, Jett, has eyes that are the color of the morning sky. I remember when my son first smiled at me. I remember his first words. I remember when he first grabbed my hands in his tiny ones and squeezed them. When my beautiful son was 5, his doctor told me he had Duchenne’s Muscular Dystrophy. I didn’t know anything about this disease. I learned quickly. He, like many other boys before him, would slowly waste away, his muscles being eaten away by a genetic defect. All of these boys would die. There was no cure, and all we could do was wait.
When my beautiful son was 7, he began to slow down, he could not run as quickly. He didn’t know why he was slower than his friends, and we could do nothing. When he was 8, he began to fall down. At 9, he needed a scooter to get around. As the years passed, my beautiful son fell more and more. When Jett was 14, he fell hard in the shower and he told me that he couldn’t take it anymore. He asked me why this happened to him, did he do something wrong, did we? My beautiful son lives in a wheelchair now. He can no longer feed himself. He can barely use his hands at all anymore. He asked me the other day, “Mom, can you hug me, because I can’t hug you anymore.”My beautiful son was born on October 12, 1995. He likes a girl named Courtney. He dreams of being a good father one day, because he thinks that is the very best thing a man can be. But he thinks he will die in a few years, or maybe less. He said to me the other day that he can’t believe in God, because God would not do this to him. So he no longer prays…
But I pray. I pray every night, as I lay awake and stare into the darkness. I don’t sleep anymore. I pray that I am doing everything I can to save my son’s life. I pray that I can save him. I pray he will get a medication that may save him. I pray that I will watch him grow old, get married and have children. I pray that he will see his next birthday. I pray for more moments for him, for us, for all of the boys that have this disease. Life is a series of moments, each precious, each filled with possibility.
At this moment, we stand at the edge of a precipice. In front of us lies a new medication, a medication that seems like it could be a cure for Duchenne. 12 lucky boys have been on this medication for over 120 weeks. There are no side effects. They are not getting worse, they are getting better. Their muscles are no longer wasting away. I know in my heart that if my son could get this medication, his disease might be stabilized. He lung muscles could stay strong, and his heart would keep beating. He might live. Why can’t he get this medication? Despite the FDASIA mandate to accelerate approval for new, breakthrough therapy that show early promise, the FDA is delaying the approval of this drug, and with it, my son’s chance for a therapy that could save his life. As the FDA sifts through paperwork, and more and more bureaucracy, our children are dying. Our children. My son. My beautiful son is dying, while people in offices across the Potomac are sifting through paperwork. By what right can these people delay my son’s access to this medication? By what right?
We named our son “Jett” because it was a strong name, and we wanted our boy to have a name that everyone would remember. Please remember him. And remember all of the boys and their parents and families that lay awake at night and wait for access to a drug that is just beyond their grasp. ”
Mindy Leffler, Aidan’s mom
My name is Mindy Leffler, and I am from Seattle, Washington. I am the mother of Aidan, who is ten years old. Aidan wants more than anything to dedicate his life to the preservation of jaguars. For the past two years, he has been flying from Seattle to Vancouver, BC every Wednesday in order to participate in a clinical trial that was eventually halted. He is part of the generation that is being asked to sacrifice his childhood to advance science on behalf of the boys who are younger than him and boys who are yet to be born.
When Aidan was diagnosed, I dug into the science because no matter what happened, I wanted to be able to tell him that I had done everything I could. As parents, not only are we educating ourselves on the science, we are funding research to the tune of millions of dollars, and in some cases, we are actually purchasing drugs and taking them through the development process ourselves.We are here today because Congress has a role to play as well. You all have spent years funding research and passing policy that’s designed to get treatments to the patients that need them in a timely way. And we are now in a time where all of those efforts have come to fruition, and the FDA is standing in the way.
Two years ago, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA) as a special tool designed to expedite drug development past the normally decade-long process it normally takes to get a drug to market. FDASIA establishes the following criteria:
That the disease is rare and deadly
That it acknowledge a surrogate marker that is reasonably likely to predict clinical benefit for patients
That it look at the balance of risk versus benefit and take patient opinion into account
Eteplirsen meets all of these criteria.
A year ago, we as parents starting meeting with the FDA to explain the need to get Eteplirsen to patients as quickly as possible. Last summer, we had hope for the first time; FDA told the company that they were open to a new drug application. But in November, FDA abruptly reversed it’s decision with no scientifically-valid explanation. And after five meetings, we moms realized that we needed help. And so we enlisted the world’s most renowned doctors in the treatment and research of Duchenne. We met with the FDA yesterday with four additional experts, but in front of you today are Dr. Kunkel, the man who led the team that originally discovered the dystrophin gene, Dr. Wilton, the man who first accomplished exon skipping in the lab, and Dr. Mendell, the primary investigator of the Eteplirsen study and the man who has been a primary investigator on more clinical trials for Duchenne than any doctor in the world.
The FDA is ignoring something that is both obvious and extraordinary. And I will let these world renowned experts in Duchenne tell you why.
Tracy Seckler, Charley’s mom
Charley I’m Tracy Seckler and my son Charley has Duchenne. You have just heard from three of the world’s top experts that Eteplirsen is safe and effectively produces the protein that boys with Duchenne are missing. I just want to take a moment to reiterate the caliber of these experts, and the weight of their collective experience and accomplishments in the field of Duchenne. Their faces don’t look familiar to you, but in our world these guys are rock stars. Together Drs. Mendell, Kunkel and Wilton have been studying this disease and treating patients for a collective 95 years. They have written more papers, conducted more clinical trials, and treated more children than any doctors worldwide. They have travelled here from Boston, Columbus and Perth not out of sympathy, not because they feel bad for us parents but because in all their years of working on Duchenne, they have never seen results like this in a clinical trial.
I want to lay out two timelines so you can understand what happens if the FDA acts as authorized and uses the Accelerated Approval approach, and the consequences if the FDA fails to do so.
If FDA grants Accelerated Approval, Eteplirsen will be available by the end of the year. 13% of boys with Duchenne can benefit from this drug. My son is not in that group, but the company plans to develop additional new medicines very similar to Eteplirsen once the regulatory path for this first drug is clear. If FDA grants accelerated approval for Eteplirsen, the other drugs will get underway quickly and treatments will be developed for 85% of boys with Duchenne within the next several years. My son will live.
If FDA requires business as usual — a full phase 3 trial — it means no access to this therapy until 2018. That’s a 4-year delay for the kids who can benefit from this drug. Four years is too late to save Jett’s life. Four years is too late to keep Aidan out of a permanent wheelchair. Four years is too late for every boy when the data we already have show that the drug is safe and effective. And it will be a decade or more before my own son sees a treatment. My son will likely die.
If a traditional phase 3 trial is required, it means boys in the placebo arm will lose muscle function permanently while we watch them decline in the name of science. It means the children in the trial would have to undergo muscle biopsies to measure dystrophin production. Biopsies are painful, invasive surgical procedures requiring general anesthesia. And they take muscle tissue, the very thing these boys cannot afford to lose. And those are the “lucky” ones in the trial. For all the boys not in the trial, it means helplessly waiting years for corroborative results while losing the ability to climb up and down stairs, to walk, to hug, to breathe.
This business as usual path means certain loss of function and inevitable death for many boys — because this disease is progressive and it is 100% fatal.
Here is a therapy that is safe and effective and a prime candidate for Accelerated Approval. Eteplirsen could be made available this year to all eligible children while the scientists and regulators continue to monitor patients to ensure the drug is safe and working. We are not asking for special treatment or to bend the rules. How does Eteplirsen measure up against other drugs that have received Accelerated Approval? It meets and even exceeds the bar. We are asking FDA officials to follow the law. And we are asking them to do it now. One of the slides Dr. Mendell showed you demonstrates that after 48 weeks on Eteplirsen, treated patients fared better than boys on placebo. That was in October 2012. Since then, patient advocates have met with the FDA six times.
Our kids are missing dystrophin, which is a tragedy. But our government is missing the opportunity to change that, which is a travesty — a travesty of justice that you can help change.
Austin and Max My name is Jenn McNary, I have two sons with Duchenne. Austin is 15 and Max is 12. We are not so much in a race against the science as we are in a race against the clock. We absolutely will find a treatment for Duchenne- but will we find it in time for the families sitting in this room? In my home , I am faced with a stark reality on a daily basis, I have one son who is on Eteplirsen, and one who is not. While Max gains independence, Austin is becoming totally dependent- at this moment he is losing his ability to feed himself. We have a unique opportunity. This generation of children could be the last generation of children to die from or the first generation to survive Duchenne. We are that close.
But it will only happen if the FDA does the right thing, listens to the researchers, examines the science and operates under the provisions of FDASIA (Food and Drug Administration Safety and Innovation Act). We are asking Congress to exercise its oversight of the FDA and to make sure the FDA is using tools like the Accelerated Approval pathway the way Congress intended, for treatments like Eteplirsen. The time is now. Please take this information back to your Members of Congress and your Senators, and be on the right side of history. If you act, you can be the hero of this story. Thank you
Many exciting programs going on. This one could be a big winner
I'm not sure what has confused you fella or why you need me to back up my statement. You just have to listen to the presentation. Did you listen to the presentation?
Do they know the data? I thought if they did the company is required to report it within a certain time frame, no?
I am not sure why there is so much animosity between ARWR longs and TKMR longs. Both stocks have done incredibly well so kudos to everyone who made money. I believe there is more to be made. Long TKMR and ARWR (admittedly I own more TKMR)