You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....
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Vertex drugs show promise with DF508
- Thread starter LisaGreene
- Start date
You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>hmw</b></i>
How much did sweat chloride levels drop during the same stage of the trial process w/ 770? If there was an early, much larger response in sweat chloride levels in those on 770 alone (the G551D population) is it due to comparison between the two trials that there wasn't a different response on the market?</end quote></div><br><br>It could be. I found the press release from the first Phase 2 trail for the G551D population (also a 14-day study):<br><a target="" title="" href="http://investors.vrtx.com/releasedetail.cfm?releaseid=301749"><br>http://investors.vrtx.com/releasedetail.cfm?releaseid=301749</a><br><br>From that press release: "In patients receiving the highest dose of VX-770
(150mg twice daily) in the Phase 2a study, sweat chloride
decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L
over the 14-day dosing period (pless than0.0001). Six of 8
patients in the 150 mg dose group achieved a decrease in sweat
chloride to below 60 mmol/L."<br><br>So the average decrease in sweat chloride was 42 mmol/L in the G551D population (using 770 alone), compared to 13 mmol/L in the dF508 population (using 809+770).<br><br>Edited to add: Whoops, I kind-of misspoke because, although they were both 14-day studies, 770+809 was only used in combo for 7 days, so you can't totally compare the two studies. I still thought it was interesting to compare, though.<br>
How much did sweat chloride levels drop during the same stage of the trial process w/ 770? If there was an early, much larger response in sweat chloride levels in those on 770 alone (the G551D population) is it due to comparison between the two trials that there wasn't a different response on the market?</end quote></div><br><br>It could be. I found the press release from the first Phase 2 trail for the G551D population (also a 14-day study):<br><a target="" title="" href="http://investors.vrtx.com/releasedetail.cfm?releaseid=301749"><br>http://investors.vrtx.com/releasedetail.cfm?releaseid=301749</a><br><br>From that press release: "In patients receiving the highest dose of VX-770
(150mg twice daily) in the Phase 2a study, sweat chloride
decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L
over the 14-day dosing period (pless than0.0001). Six of 8
patients in the 150 mg dose group achieved a decrease in sweat
chloride to below 60 mmol/L."<br><br>So the average decrease in sweat chloride was 42 mmol/L in the G551D population (using 770 alone), compared to 13 mmol/L in the dF508 population (using 809+770).<br><br>Edited to add: Whoops, I kind-of misspoke because, although they were both 14-day studies, 770+809 was only used in combo for 7 days, so you can't totally compare the two studies. I still thought it was interesting to compare, though.<br>
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>hmw</b></i>
How much did sweat chloride levels drop during the same stage of the trial process w/ 770? If there was an early, much larger response in sweat chloride levels in those on 770 alone (the G551D population) is it due to comparison between the two trials that there wasn't a different response on the market?</end quote><br><br>It could be. I found the press release from the first Phase 2 trail for the G551D population (also a 14-day study):<br><a target="" title="" href="http://investors.vrtx.com/releasedetail.cfm?releaseid=301749"><br>http://investors.vrtx.com/releasedetail.cfm?releaseid=301749</a><br><br>From that press release: "In patients receiving the highest dose of VX-770
(150mg twice daily) in the Phase 2a study, sweat chloride
decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L
over the 14-day dosing period (pless than0.0001). Six of 8
patients in the 150 mg dose group achieved a decrease in sweat
chloride to below 60 mmol/L."<br><br>So the average decrease in sweat chloride was 42 mmol/L in the G551D population (using 770 alone), compared to 13 mmol/L in the dF508 population (using 809+770).<br><br>Edited to add: Whoops, I kind-of misspoke because, although they were both 14-day studies, 770+809 was only used in combo for 7 days, so you can't totally compare the two studies. I still thought it was interesting to compare, though.<br>
How much did sweat chloride levels drop during the same stage of the trial process w/ 770? If there was an early, much larger response in sweat chloride levels in those on 770 alone (the G551D population) is it due to comparison between the two trials that there wasn't a different response on the market?</end quote><br><br>It could be. I found the press release from the first Phase 2 trail for the G551D population (also a 14-day study):<br><a target="" title="" href="http://investors.vrtx.com/releasedetail.cfm?releaseid=301749"><br>http://investors.vrtx.com/releasedetail.cfm?releaseid=301749</a><br><br>From that press release: "In patients receiving the highest dose of VX-770
(150mg twice daily) in the Phase 2a study, sweat chloride
decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L
over the 14-day dosing period (pless than0.0001). Six of 8
patients in the 150 mg dose group achieved a decrease in sweat
chloride to below 60 mmol/L."<br><br>So the average decrease in sweat chloride was 42 mmol/L in the G551D population (using 770 alone), compared to 13 mmol/L in the dF508 population (using 809+770).<br><br>Edited to add: Whoops, I kind-of misspoke because, although they were both 14-day studies, 770+809 was only used in combo for 7 days, so you can't totally compare the two studies. I still thought it was interesting to compare, though.<br>
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>hmw</b></i>
How much did sweat chloride levels drop during the same stage of the trial process w/ 770? If there was an early, much larger response in sweat chloride levels in those on 770 alone (the G551D population) is it due to comparison between the two trials that there wasn't a different response on the market?</end quote><br><br>It could be. I found the press release from the first Phase 2 trail for the G551D population (also a 14-day study):<br><a target="" title="" href="http://investors.vrtx.com/releasedetail.cfm?releaseid=301749"><br>http://investors.vrtx.com/releasedetail.cfm?releaseid=301749</a><br><br>From that press release: "In patients receiving the highest dose of VX-770
(150mg twice daily) in the Phase 2a study, sweat chloride
decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L
over the 14-day dosing period (pless than0.0001). Six of 8
patients in the 150 mg dose group achieved a decrease in sweat
chloride to below 60 mmol/L."<br><br>So the average decrease in sweat chloride was 42 mmol/L in the G551D population (using 770 alone), compared to 13 mmol/L in the dF508 population (using 809+770).<br><br>Edited to add: Whoops, I kind-of misspoke because, although they were both 14-day studies, 770+809 was only used in combo for 7 days, so you can't totally compare the two studies. I still thought it was interesting to compare, though.<br>
How much did sweat chloride levels drop during the same stage of the trial process w/ 770? If there was an early, much larger response in sweat chloride levels in those on 770 alone (the G551D population) is it due to comparison between the two trials that there wasn't a different response on the market?</end quote><br><br>It could be. I found the press release from the first Phase 2 trail for the G551D population (also a 14-day study):<br><a target="" title="" href="http://investors.vrtx.com/releasedetail.cfm?releaseid=301749"><br>http://investors.vrtx.com/releasedetail.cfm?releaseid=301749</a><br><br>From that press release: "In patients receiving the highest dose of VX-770
(150mg twice daily) in the Phase 2a study, sweat chloride
decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L
over the 14-day dosing period (pless than0.0001). Six of 8
patients in the 150 mg dose group achieved a decrease in sweat
chloride to below 60 mmol/L."<br><br>So the average decrease in sweat chloride was 42 mmol/L in the G551D population (using 770 alone), compared to 13 mmol/L in the dF508 population (using 809+770).<br><br>Edited to add: Whoops, I kind-of misspoke because, although they were both 14-day studies, 770+809 was only used in combo for 7 days, so you can't totally compare the two studies. I still thought it was interesting to compare, though.<br>
Thank you Kristen! That makes sense. Even if the first study was slightly longer, that was a very substantial difference and I am sure the investors did look at that.
<br>
<br><div class="FTQUOTE"><begin quote>Doing some simple math ( (8*15 + 4*20 + 5*x)/17=13 ) I received following results:
<br>
<br>47% people (8/17) with a reduction of sweat chloride that exceeded -15.0 mmol/L
<br>23% people (4/17) with a reduction of sweat chloride that exceeded -20.0 mmol/L
<br>
<br>BUT
<br>29% people (5/17) with a reduction of sweat chloride that exceeded ONLY -4.2 mmol/L
<br>
<br>and I think this could be also a reason for such reactions of investors</end quote></div>
<br>Four individuals did not have 'evaluable data' and were not included in responder analysis, so the math needs to be done excluding them. I don't like thinking about what that does to the averages of the rest of the participants- it seems this trial shows a very wide of responses. I agree with the post mentioning the significance of modifier genes.
<br>
<br><div class="FTQUOTE"><begin quote>You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....</end quote></div>
<br>To clarify- at this point, treating either mutation will help modify disease course (improve lung function, slow progression, etc.) It will not eliminate the need for treatments or bring you to the condition of an asymptomatic, unaffected carrier.
<br>
<br>
<br>
<br>
<br><div class="FTQUOTE"><begin quote>Doing some simple math ( (8*15 + 4*20 + 5*x)/17=13 ) I received following results:
<br>
<br>47% people (8/17) with a reduction of sweat chloride that exceeded -15.0 mmol/L
<br>23% people (4/17) with a reduction of sweat chloride that exceeded -20.0 mmol/L
<br>
<br>BUT
<br>29% people (5/17) with a reduction of sweat chloride that exceeded ONLY -4.2 mmol/L
<br>
<br>and I think this could be also a reason for such reactions of investors</end quote></div>
<br>Four individuals did not have 'evaluable data' and were not included in responder analysis, so the math needs to be done excluding them. I don't like thinking about what that does to the averages of the rest of the participants- it seems this trial shows a very wide of responses. I agree with the post mentioning the significance of modifier genes.
<br>
<br><div class="FTQUOTE"><begin quote>You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....</end quote></div>
<br>To clarify- at this point, treating either mutation will help modify disease course (improve lung function, slow progression, etc.) It will not eliminate the need for treatments or bring you to the condition of an asymptomatic, unaffected carrier.
<br>
<br>
<br>
Thank you Kristen! That makes sense. Even if the first study was slightly longer, that was a very substantial difference and I am sure the investors did look at that.
<br>
<br><div class="FTQUOTE"><begin quote>Doing some simple math ( (8*15 + 4*20 + 5*x)/17=13 ) I received following results:
<br>
<br>47% people (8/17) with a reduction of sweat chloride that exceeded -15.0 mmol/L
<br>23% people (4/17) with a reduction of sweat chloride that exceeded -20.0 mmol/L
<br>
<br>BUT
<br>29% people (5/17) with a reduction of sweat chloride that exceeded ONLY -4.2 mmol/L
<br>
<br>and I think this could be also a reason for such reactions of investors</end quote>
<br>Four individuals did not have 'evaluable data' and were not included in responder analysis, so the math needs to be done excluding them. I don't like thinking about what that does to the averages of the rest of the participants- it seems this trial shows a very wide of responses. I agree with the post mentioning the significance of modifier genes.
<br>
<br><div class="FTQUOTE"><begin quote>You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....</end quote>
<br>To clarify- at this point, treating either mutation will help modify disease course (improve lung function, slow progression, etc.) It will not eliminate the need for treatments or bring you to the condition of an asymptomatic, unaffected carrier.
<br>
<br>
<br>
<br>
<br><div class="FTQUOTE"><begin quote>Doing some simple math ( (8*15 + 4*20 + 5*x)/17=13 ) I received following results:
<br>
<br>47% people (8/17) with a reduction of sweat chloride that exceeded -15.0 mmol/L
<br>23% people (4/17) with a reduction of sweat chloride that exceeded -20.0 mmol/L
<br>
<br>BUT
<br>29% people (5/17) with a reduction of sweat chloride that exceeded ONLY -4.2 mmol/L
<br>
<br>and I think this could be also a reason for such reactions of investors</end quote>
<br>Four individuals did not have 'evaluable data' and were not included in responder analysis, so the math needs to be done excluding them. I don't like thinking about what that does to the averages of the rest of the participants- it seems this trial shows a very wide of responses. I agree with the post mentioning the significance of modifier genes.
<br>
<br><div class="FTQUOTE"><begin quote>You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....</end quote>
<br>To clarify- at this point, treating either mutation will help modify disease course (improve lung function, slow progression, etc.) It will not eliminate the need for treatments or bring you to the condition of an asymptomatic, unaffected carrier.
<br>
<br>
<br>
Thank you Kristen! That makes sense. Even if the first study was slightly longer, that was a very substantial difference and I am sure the investors did look at that.
<br>
<br><div class="FTQUOTE"><begin quote>Doing some simple math ( (8*15 + 4*20 + 5*x)/17=13 ) I received following results:
<br>
<br>47% people (8/17) with a reduction of sweat chloride that exceeded -15.0 mmol/L
<br>23% people (4/17) with a reduction of sweat chloride that exceeded -20.0 mmol/L
<br>
<br>BUT
<br>29% people (5/17) with a reduction of sweat chloride that exceeded ONLY -4.2 mmol/L
<br>
<br>and I think this could be also a reason for such reactions of investors</end quote>
<br>Four individuals did not have 'evaluable data' and were not included in responder analysis, so the math needs to be done excluding them. I don't like thinking about what that does to the averages of the rest of the participants- it seems this trial shows a very wide of responses. I agree with the post mentioning the significance of modifier genes.
<br>
<br><div class="FTQUOTE"><begin quote>You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....</end quote>
<br>To clarify- at this point, treating either mutation will help modify disease course (improve lung function, slow progression, etc.) It will not eliminate the need for treatments or bring you to the condition of an asymptomatic, unaffected carrier.
<br>
<br>
<br>
<br>
<br><div class="FTQUOTE"><begin quote>Doing some simple math ( (8*15 + 4*20 + 5*x)/17=13 ) I received following results:
<br>
<br>47% people (8/17) with a reduction of sweat chloride that exceeded -15.0 mmol/L
<br>23% people (4/17) with a reduction of sweat chloride that exceeded -20.0 mmol/L
<br>
<br>BUT
<br>29% people (5/17) with a reduction of sweat chloride that exceeded ONLY -4.2 mmol/L
<br>
<br>and I think this could be also a reason for such reactions of investors</end quote>
<br>Four individuals did not have 'evaluable data' and were not included in responder analysis, so the math needs to be done excluding them. I don't like thinking about what that does to the averages of the rest of the participants- it seems this trial shows a very wide of responses. I agree with the post mentioning the significance of modifier genes.
<br>
<br><div class="FTQUOTE"><begin quote>You only need one mutation of the specified mutations (either G551D for VX-770 or dd508 for VX-809/VX-770). Even if you have some other obscure mutation, as long as one of them is one of the aforementioned, the drug will apply to you. In essence, "treating" one mutation would make you something more of a CF carrier....</end quote>
<br>To clarify- at this point, treating either mutation will help modify disease course (improve lung function, slow progression, etc.) It will not eliminate the need for treatments or bring you to the condition of an asymptomatic, unaffected carrier.
<br>
<br>
<br>
I was also pretty confused about the stock sell-off and the interpretation of these results. My brother owns stock in Vertex and was equally confused. He came across this article that I think is a pretty good analysis of what happened with investors.
http://seekingalpha.com/article/274642-vertex-first-drugs-ever-to-target-root-cause-of-cystic-fibrosis
http://seekingalpha.com/article/274642-vertex-first-drugs-ever-to-target-root-cause-of-cystic-fibrosis
I was also pretty confused about the stock sell-off and the interpretation of these results. My brother owns stock in Vertex and was equally confused. He came across this article that I think is a pretty good analysis of what happened with investors.
http://seekingalpha.com/article/274642-vertex-first-drugs-ever-to-target-root-cause-of-cystic-fibrosis
http://seekingalpha.com/article/274642-vertex-first-drugs-ever-to-target-root-cause-of-cystic-fibrosis
I was also pretty confused about the stock sell-off and the interpretation of these results. My brother owns stock in Vertex and was equally confused. He came across this article that I think is a pretty good analysis of what happened with investors.
<br />
<br />http://seekingalpha.com/article/274642-vertex-first-drugs-ever-to-target-root-cause-of-cystic-fibrosis
<br />
<br />http://seekingalpha.com/article/274642-vertex-first-drugs-ever-to-target-root-cause-of-cystic-fibrosis
Don't forget that VX-661 (a second "corrector") is also in the pipeline. From what I have heard (I am very close with our CF chapter director who is "in the loop" with Dr. Beal, etc) it sounds like Vertex has learned ALOT about the CF cell function in the past several years through drugs like VX770 and 809... and in their research they believe that it will take a 3rd corrector to really do the job for the DF508 mutation -- enter VX661.
"VX-661 is the third potential new medicine for CF to emerge from Vertex's CF research efforts. As a corrector, VX-661 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. In in vitro studies, a combination of VX-661 and VX-770 resulted in greater CFTR activity, as compared to treatment with VX-661 alone. Vertex plans to initiate a Phase 2 study of VX-661 by the end of 2011. "
"VX-661 is the third potential new medicine for CF to emerge from Vertex's CF research efforts. As a corrector, VX-661 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. In in vitro studies, a combination of VX-661 and VX-770 resulted in greater CFTR activity, as compared to treatment with VX-661 alone. Vertex plans to initiate a Phase 2 study of VX-661 by the end of 2011. "
Don't forget that VX-661 (a second "corrector") is also in the pipeline. From what I have heard (I am very close with our CF chapter director who is "in the loop" with Dr. Beal, etc) it sounds like Vertex has learned ALOT about the CF cell function in the past several years through drugs like VX770 and 809... and in their research they believe that it will take a 3rd corrector to really do the job for the DF508 mutation -- enter VX661.
"VX-661 is the third potential new medicine for CF to emerge from Vertex's CF research efforts. As a corrector, VX-661 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. In in vitro studies, a combination of VX-661 and VX-770 resulted in greater CFTR activity, as compared to treatment with VX-661 alone. Vertex plans to initiate a Phase 2 study of VX-661 by the end of 2011. "
"VX-661 is the third potential new medicine for CF to emerge from Vertex's CF research efforts. As a corrector, VX-661 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. In in vitro studies, a combination of VX-661 and VX-770 resulted in greater CFTR activity, as compared to treatment with VX-661 alone. Vertex plans to initiate a Phase 2 study of VX-661 by the end of 2011. "
Don't forget that VX-661 (a second "corrector") is also in the pipeline. From what I have heard (I am very close with our CF chapter director who is "in the loop" with Dr. Beal, etc) it sounds like Vertex has learned ALOT about the CF cell function in the past several years through drugs like VX770 and 809... and in their research they believe that it will take a 3rd corrector to really do the job for the DF508 mutation -- enter VX661.
<br />
<br />"VX-661 is the third potential new medicine for CF to emerge from Vertex's CF research efforts. As a corrector, VX-661 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. In in vitro studies, a combination of VX-661 and VX-770 resulted in greater CFTR activity, as compared to treatment with VX-661 alone. Vertex plans to initiate a Phase 2 study of VX-661 by the end of 2011. "
<br />
<br />
<br />
<br />
<br />
<br />"VX-661 is the third potential new medicine for CF to emerge from Vertex's CF research efforts. As a corrector, VX-661 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. In in vitro studies, a combination of VX-661 and VX-770 resulted in greater CFTR activity, as compared to treatment with VX-661 alone. Vertex plans to initiate a Phase 2 study of VX-661 by the end of 2011. "
<br />
<br />
<br />
<br />
BaggedCereals
New member
I am looking forward to seeing whats done for the F508's
BaggedCereals
New member
I am looking forward to seeing whats done for the F508's
BaggedCereals
New member
I am looking forward to seeing whats done for the F508's