3 ms·

Approving a Muscular Dystrophy Drug Ignites a Civil War at the FDA

13 points by adenadel 10y ago

mikeyouse 10y ago
Derek Lowe -- Of the fantastic "In The Pipeline" blog with Science disagrees with the FDA approval; http://blogs.sciencemag.org/pipeline/archives/2016/09/20/sarepta-gets-an-approval-unfortunately http://blogs.sciencemag.org/pipeline/archives/2016/09/20/sar... He's an excellent read if anyone wants to keep up with things in the Pharma and regulatory world. He's probably more famous for his "Things I Won't Work With" series that I've seen linked to a few times on HN. > And he’s just getting warmed up, if that’s the right phrase to use for something that detonates things at -180C (that’s -300 Fahrenheit, if you only have a kitchen thermometer). The great majority of Streng’s reactions have surely never been run again. The paper goes on to react FOOF with everything else you wouldn’t react it with: ammonia (“vigorous”, this at 100K), water ice (explosion, natch), chlorine (“violent explosion”, so he added it more slowly the second time), red phosphorus (not good), bromine fluoride, chlorine trifluoride (say what?), perchloryl fluoride (!), tetrafluorohydrazine (how on Earth. . .), and on, and on. If the paper weren’t laid out in complete grammatical sentences and published in JACS, you’d swear it was the work of a violent lunatic. http://blogs.sciencemag.org/pipeline/archives/2010/02/23/things_i_wont_work_with_dioxygen_difluoride http://blogs.sciencemag.org/pipeline/archives/2010/02/23/thi...
pcvarmint 10y ago
This article has many scientific gaffes: because the genetic defect that causes Duchenne is on the X chromosome, it is a disease of boys. It is because it is an X-Linked-Recessive trait that it a disease of boys. Saying "because [it] is on the X chromosome" adds no value by itself. If it were "because [it] is on the Y chromosome", then it would sufficiently follow that it was restricted to boys (with rare exceptions). The data showed an increase of only 0.28% of normal levels, which was, on average, a tripling of dystrophin levels for these boys. I have no idea what to make of this. "Increase of only 0.28%" == "on average, a tripling"? Unger was worried about the unknown risks of the drug, as well as the risks to boys who might get injection ports while they were also on immune-suppressing steroids, raising the risk of injection (sic).
- Declanomous 10y ago
  I don't see an issue with the statements that were made. An increase in dystrophin levels to .28% of normal levels, indicates that without the drug, the dystrophin level was at .093% of normal levels. (.093% * 3 = .28%) The drug succeeds at raising dystrophin levels, but the levels are still well below those of a healthy individual. (Which is the center-point of the whole debate) A recessive x-linked trait will be more likely in men than women, because men have one x chromosome, and women have two. This means that a male with an x-chromosome with the Duchenne gene will always have Duchenne, whereas a woman would need a copy on each of her x chromosomes, assuming the woman isn't XY with androgen insensitivity, or XXY, etc. A common example of an x-recessive trait would be colorblindness. Genetic colorblindness affects about 8% of men and .5% of women. Since men always have colorblindness if they carry the gene, we can use the prevalence in men as the population prevalence, assuming colorblindness doesn't play a role in sexual selection (doubtful, given the fact that fashion sense probably plays a role). .08.08 = .0064, which is pretty close to the prevalence of colorblindness in women. Duchenne affects 1/3600 men. Assuming 1/3600 is the prevalence of the gene in the population, we'd expect 1/3600 1/3600 = 1/12960000, or 1 in thirteen million women to have it. So we'd expect about 25 female cases in the US, and about 83000 male cases. Edit: This is assuming having two Duchenne genes will still lead to Duchenne. If 3x normal levels of dystrophin leads to clinical relief, it's possible that having two genes allows for enough dystrophin production to prevent Duchenne. I don't know enough about the pathways involved, but it's possible.

13 points by adenadel 10y ago

Derek Lowe -- Of the fantastic "In The Pipeline" blog with Science disagrees with the FDA approval; http://blogs.sciencemag.org/pipeline/archives/2016/09/20/sarepta-gets-an-approval-unfortunately http://blogs.sciencemag.org/pipeline/archives/2016/09/20/sar... He's an excellent read if anyone wants to keep up with things in the Pharma and regulatory world. He's probably more famous for his "Things I Won't Work With" series that I've seen linked to a few times on HN. > And he’s just getting warmed up, if that’s the right phrase to use for something that detonates things at -180C (that’s -300 Fahrenheit, if you only have a kitchen thermometer). The great majority of Streng’s reactions have surely never been run again. The paper goes on to react FOOF with everything else you wouldn’t react it with: ammonia (“vigorous”, this at 100K), water ice (explosion, natch), chlorine (“violent explosion”, so he added it more slowly the second time), red phosphorus (not good), bromine fluoride, chlorine trifluoride (say what?), perchloryl fluoride (!), tetrafluorohydrazine (how on Earth. . .), and on, and on. If the paper weren’t laid out in complete grammatical sentences and published in JACS, you’d swear it was the work of a violent lunatic. http://blogs.sciencemag.org/pipeline/archives/2010/02/23/things_i_wont_work_with_dioxygen_difluoride http://blogs.sciencemag.org/pipeline/archives/2010/02/23/thi...

pcvarmint 10y ago

This article has many scientific gaffes: because the genetic defect that causes Duchenne is on the X chromosome, it is a disease of boys. It is because it is an X-Linked-Recessive trait that it a disease of boys. Saying "because [it] is on the X chromosome" adds no value by itself. If it were "because [it] is on the Y chromosome", then it would sufficiently follow that it was restricted to boys (with rare exceptions). The data showed an increase of only 0.28% of normal levels, which was, on average, a tripling of dystrophin levels for these boys. I have no idea what to make of this. "Increase of only 0.28%" == "on average, a tripling"? Unger was worried about the unknown risks of the drug, as well as the risks to boys who might get injection ports while they were also on immune-suppressing steroids, raising the risk of injection (sic).

Declanomous 10y ago
I don't see an issue with the statements that were made. An increase in dystrophin levels to .28% of normal levels, indicates that without the drug, the dystrophin level was at .093% of normal levels. (.093% * 3 = .28%) The drug succeeds at raising dystrophin levels, but the levels are still well below those of a healthy individual. (Which is the center-point of the whole debate) A recessive x-linked trait will be more likely in men than women, because men have one x chromosome, and women have two. This means that a male with an x-chromosome with the Duchenne gene will always have Duchenne, whereas a woman would need a copy on each of her x chromosomes, assuming the woman isn't XY with androgen insensitivity, or XXY, etc. A common example of an x-recessive trait would be colorblindness. Genetic colorblindness affects about 8% of men and .5% of women. Since men always have colorblindness if they carry the gene, we can use the prevalence in men as the population prevalence, assuming colorblindness doesn't play a role in sexual selection (doubtful, given the fact that fashion sense probably plays a role). .08.08 = .0064, which is pretty close to the prevalence of colorblindness in women. Duchenne affects 1/3600 men. Assuming 1/3600 is the prevalence of the gene in the population, we'd expect 1/3600 1/3600 = 1/12960000, or 1 in thirteen million women to have it. So we'd expect about 25 female cases in the US, and about 83000 male cases. Edit: This is assuming having two Duchenne genes will still lead to Duchenne. If 3x normal levels of dystrophin leads to clinical relief, it's possible that having two genes allows for enough dystrophin production to prevent Duchenne. I don't know enough about the pathways involved, but it's possible.