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| Once in limbo, promising Duchenne muscular dystrophy drug back on track toward approval | |
| (about 14 hours later) | |
| A new drug designed to slow the progression of Duchenne muscular dystrophy, a devastating disease that overwhelmingly affects boys and typically leaves them needing wheelchairs by their teens and dead in their 20s, has received a long-awaited boost from the Food and Drug Administration. | A new drug designed to slow the progression of Duchenne muscular dystrophy, a devastating disease that overwhelmingly affects boys and typically leaves them needing wheelchairs by their teens and dead in their 20s, has received a long-awaited boost from the Food and Drug Administration. |
| Massachusetts-based Sarepta Therapeutics said Monday that FDA officials detailed a potential path forward for the drug, eteplirsen, and indicated a willingness to consider it for accelerated approval. The news puts eteplirsen one step closer to becoming the first approved treatment for Duchenne, a disease that affects about one in 3,500 boys globally. | Massachusetts-based Sarepta Therapeutics said Monday that FDA officials detailed a potential path forward for the drug, eteplirsen, and indicated a willingness to consider it for accelerated approval. The news puts eteplirsen one step closer to becoming the first approved treatment for Duchenne, a disease that affects about one in 3,500 boys globally. |
| “This provides the opportunity to get the drug approved and in the hands of all the boys who can benefit from it sometime in 2015,” Sarepta chief executive Chris Garabedian said in an interview. “I think that’s a huge win for the [Duchenne] community and for Sarepta.” | “This provides the opportunity to get the drug approved and in the hands of all the boys who can benefit from it sometime in 2015,” Sarepta chief executive Chris Garabedian said in an interview. “I think that’s a huge win for the [Duchenne] community and for Sarepta.” |
| The move follows a tumultuous year in which the FDA initially appeared headed toward swift approval of eteplirsen based on promising results from a trial involving 12 young boys, whose muscular deterioration seemed virtually halted by the drug. But the agency hit the pause button in November, saying it would be “premature” for Sarepta to seek approval of its drug after the failure of a separate trial involving a different Duchenne treatment that used similar technology. | The move follows a tumultuous year in which the FDA initially appeared headed toward swift approval of eteplirsen based on promising results from a trial involving 12 young boys, whose muscular deterioration seemed virtually halted by the drug. But the agency hit the pause button in November, saying it would be “premature” for Sarepta to seek approval of its drug after the failure of a separate trial involving a different Duchenne treatment that used similar technology. |
| Months of behind-the-scenes deliberations followed over the effectiveness of eteplirsen, as well as an aggressive public campaign waged by patients’ families determined to keep pressure on the agency. Families met with top FDA officials repeatedly, filed a White House petition in support of the drug’s approval, posted online videos of boys benefiting from eteplirsen and argued that the FDA was far too slow to act on evidence that the drug was stabilizing children who otherwise would decline rapidly. | Months of behind-the-scenes deliberations followed over the effectiveness of eteplirsen, as well as an aggressive public campaign waged by patients’ families determined to keep pressure on the agency. Families met with top FDA officials repeatedly, filed a White House petition in support of the drug’s approval, posted online videos of boys benefiting from eteplirsen and argued that the FDA was far too slow to act on evidence that the drug was stabilizing children who otherwise would decline rapidly. |
| “Kids on this drug are having remarkably different lives than they would have otherwise,” Mindy Leffler of Bellevue, Wash., said in a recent interview. She has been pushing for the drug’s approval in hopes of accessing it for her 10-year-old son, Aidan, who has begun to lose function in his legs. “When you’re talking about something that has zero side effects, with good potential to work, I don’t understand the need for caution moving forward. . . . Who the hell cares, if the kid is walking when he shouldn’t be?” | “Kids on this drug are having remarkably different lives than they would have otherwise,” Mindy Leffler of Bellevue, Wash., said in a recent interview. She has been pushing for the drug’s approval in hopes of accessing it for her 10-year-old son, Aidan, who has begun to lose function in his legs. “When you’re talking about something that has zero side effects, with good potential to work, I don’t understand the need for caution moving forward. . . . Who the hell cares, if the kid is walking when he shouldn’t be?” |
| Duchenne is caused by a mutation in the gene responsible for producing dystrophin, an essential protein involved in muscle function. Without dystrophin, even routine activities can damage muscles, causing them to die and be replaced by fat and other tissue. It is typically diagnosed in boys by age 6. The steady progression of the disease leaves many boys immobile by the time they are teenagers, and eventually can affect the heart and respiratory muscles, making breathing difficult. | Duchenne is caused by a mutation in the gene responsible for producing dystrophin, an essential protein involved in muscle function. Without dystrophin, even routine activities can damage muscles, causing them to die and be replaced by fat and other tissue. It is typically diagnosed in boys by age 6. The steady progression of the disease leaves many boys immobile by the time they are teenagers, and eventually can affect the heart and respiratory muscles, making breathing difficult. |
| Eteplirsen uses an approach called exon skipping, intended to bypass the existing mutation and restore a gene’s ability to produce dystrophin. The goal is to create enough dystrophin production to transform Duchenne into a milder and more sustainable form of muscular dystrophy known as Becker. | Eteplirsen uses an approach called exon skipping, intended to bypass the existing mutation and restore a gene’s ability to produce dystrophin. The goal is to create enough dystrophin production to transform Duchenne into a milder and more sustainable form of muscular dystrophy known as Becker. |
| In more than two years since Sarepta’s clinical trial began, the results have proved encouraging. Although many questions remain about how much dystrophin the drug actually helps to produce, the drug appears to have halted the decline for the boys in the trial, while showing no adverse side effects. | In more than two years since Sarepta’s clinical trial began, the results have proved encouraging. Although many questions remain about how much dystrophin the drug actually helps to produce, the drug appears to have halted the decline for the boys in the trial, while showing no adverse side effects. |
| “It’s unequivocal. Since the day the kids were started on eteplirsen, they basically have never changed again. The natural history of the disease is to decline,” said Jerry Mendell, a pediatric expert at Nationwide Children’s Hospital in Columbus, Ohio, and the lead investigator on the Sarepta trial. “I see it as a game changer.” | “It’s unequivocal. Since the day the kids were started on eteplirsen, they basically have never changed again. The natural history of the disease is to decline,” said Jerry Mendell, a pediatric expert at Nationwide Children’s Hospital in Columbus, Ohio, and the lead investigator on the Sarepta trial. “I see it as a game changer.” |
| Only about 13 percent of Duchenne patients have mutations that could benefit from eteplirsen, but Sarepta is developing similar drugs to treat boys with other exon deletions, along with clinical trials to test them. | Only about 13 percent of Duchenne patients have mutations that could benefit from eteplirsen, but Sarepta is developing similar drugs to treat boys with other exon deletions, along with clinical trials to test them. |
| The company said Monday that even as the FDA said its evaluators “remain skeptical” about the persuasiveness of some of Sarepta’s data, the agency encouraged it to push forward later this year with a larger “confirmatory” study that would provide more robust data about eteplirsen’s safety and effectiveness. | The company said Monday that even as the FDA said its evaluators “remain skeptical” about the persuasiveness of some of Sarepta’s data, the agency encouraged it to push forward later this year with a larger “confirmatory” study that would provide more robust data about eteplirsen’s safety and effectiveness. |
| In the short term, that means as many as 100 additional patients — some older and some younger than the boys in the current trial — could gain access the drug prior to FDA approval. That study also is unlikely to have a placebo group, Garabedian said, meaning that every child enrolled will receive the drug. | In the short term, that means as many as 100 additional patients — some older and some younger than the boys in the current trial — could gain access the drug prior to FDA approval. That study also is unlikely to have a placebo group, Garabedian said, meaning that every child enrolled will receive the drug. |
| “They know that the patients are waiting for this,” said Garabedian, who has said that the drug, if approved, could be among the most expensive ever in the United States. | “They know that the patients are waiting for this,” said Garabedian, who has said that the drug, if approved, could be among the most expensive ever in the United States. |
| Not everyone faults the FDA for taking so long to decide how to proceed on eteplirsen. Eric Hoffman, director of the Center for Genetic Medicine at Children’s National Medical Center and a longtime Duchenne researcher, said valid questions remain about eteplirsen’s dystrophin-producing abilities and how effective Sarepta’s drug really is over the long term. | Not everyone faults the FDA for taking so long to decide how to proceed on eteplirsen. Eric Hoffman, director of the Center for Genetic Medicine at Children’s National Medical Center and a longtime Duchenne researcher, said valid questions remain about eteplirsen’s dystrophin-producing abilities and how effective Sarepta’s drug really is over the long term. |
| “For accelerated approval, FDA wants a compelling case, and this is a case that’s been challenging to make compelling,” Hoffman said in an interview this month. “I’ve personally been very impressed with the FDA. They’ve been extremely interactive. . . . There’s every indication they are taking this extremely seriously.” | “For accelerated approval, FDA wants a compelling case, and this is a case that’s been challenging to make compelling,” Hoffman said in an interview this month. “I’ve personally been very impressed with the FDA. They’ve been extremely interactive. . . . There’s every indication they are taking this extremely seriously.” |
| Even Louis Kunkel, a Harvard geneticist credited with discovering the gene behind Duchenne, said recently that he is “of mixed mind” on whether Sarepta has proved that eteplirsen is ready for FDA approval. On one hand, he said, the results are incredibly promising. On the other, Duchenne patients have faced many disappointments with therapies that seemed to offer hope but ultimately failed. | Even Louis Kunkel, a Harvard geneticist credited with discovering the gene behind Duchenne, said recently that he is “of mixed mind” on whether Sarepta has proved that eteplirsen is ready for FDA approval. On one hand, he said, the results are incredibly promising. On the other, Duchenne patients have faced many disappointments with therapies that seemed to offer hope but ultimately failed. |
| “I’ve waffled on my opinion of this,” Kunkel said. “If you listen to the families, they make a good argument why this should be available. . . . [But] how well it’s working is an academic argument that hasn’t been settled yet. And I think that’s where the hesitancy of the FDA is.” | “I’ve waffled on my opinion of this,” Kunkel said. “If you listen to the families, they make a good argument why this should be available. . . . [But] how well it’s working is an academic argument that hasn’t been settled yet. And I think that’s where the hesitancy of the FDA is.” |
| Earlier this month, asked about eteplirsen during an event in Boston, FDA Commissioner Margaret A. Hamburg underscored the agency’s efforts to seek input from patients and said the agency understands the urgency to find treatments for Duchenne, according to an account in the Boston Business Journal. But she defended the FDA’s deliberate process, saying, “We want to develop products that will really make a difference.” | Earlier this month, asked about eteplirsen during an event in Boston, FDA Commissioner Margaret A. Hamburg underscored the agency’s efforts to seek input from patients and said the agency understands the urgency to find treatments for Duchenne, according to an account in the Boston Business Journal. But she defended the FDA’s deliberate process, saying, “We want to develop products that will really make a difference.” |
| Despite the recent tensions between federal regulators and families affected by Duchenne, the fact that eteplirsen now has a clear path toward approval is likely to bring a measure of hope and relief for people such as Jenn McNary of Massachusetts. | Despite the recent tensions between federal regulators and families affected by Duchenne, the fact that eteplirsen now has a clear path toward approval is likely to bring a measure of hope and relief for people such as Jenn McNary of Massachusetts. |
| Her 12-year-old son, Max, has flourished during his two years in the eteplirsen trial. Without the drug, his mother said, he probably would be in a wheelchair. Instead, he is running and playing with friends and has recently tried riding a bike. Meanwhile, his 15-year-old brother, Austin, did not qualify for the Sarepta trial. He must use a wheelchair and recently began to lose the ability to feed himself. McNary believes that if Austin also can get access to the drug soon, it could halt his decline. | Her 12-year-old son, Max, has flourished during his two years in the eteplirsen trial. Without the drug, his mother said, he probably would be in a wheelchair. Instead, he is running and playing with friends and has recently tried riding a bike. Meanwhile, his 15-year-old brother, Austin, did not qualify for the Sarepta trial. He must use a wheelchair and recently began to lose the ability to feed himself. McNary believes that if Austin also can get access to the drug soon, it could halt his decline. |
| “This is about stopping the progression of the disease; this was never a cure,” McNary said. “If we could just freeze it while we let smart people figure it out further, that would be fine with me. . . . That’s the one thing that none of us have is any time to waste.” | “This is about stopping the progression of the disease; this was never a cure,” McNary said. “If we could just freeze it while we let smart people figure it out further, that would be fine with me. . . . That’s the one thing that none of us have is any time to waste.” |