Re: NATAP: QUAD-Panel Votes 13-1 To Recommend Approval--Cobicistat issues

[Guest guest]

Hi Jeton--One of the problems with cobicistat is that it makes it hard to measure creatinine levels by artificially raising the blood test measurement--even when more sensitive measures like 24-hr urine collection tell you creatinine levels haven't really changed.  So when you combine it with a drug like tenofovir that can raise creatinine levels, it's hard to know if the usual blood tests are accurate or not.  Definitely a dilemma for clinicians and patients.  In our discussions with Gilead they have refused to offer any suggestions for dealing with this dilemma--leaving it to the FDA to made the determination.   It'll be interesting to see what monitoring recommendations the FDA makes on the label, and what Phase IV post-marketing trials they end up requiring as a requirement of approval.   Naturally Gilead doesn't want to recommend any  onerous and expensive creatinine tests that might be a barrier to people taking their new wonder pill.  We've asked them for years to recommend that all pts starting tenofovir-based regimens get a baseline creatinine level before starting, and have it carefully monitored.  They defer to the expertise of prescribing clinicians--whom as we all know aren't always consistent in their practices or knowledge levels.  

Re GS-7340--the supposed advantage of this new tenofovir pro-drug is that it will require a much smaller dose--which is an obvious advantage in co-formulating, and according to Gilead will reduce kidney toxicity.  Though if it results in the same blood levels of TDF (tenofovir dixoproxil fumarate--the active compound) it's unclear why the kidney effects should be any different.  Again, the company refuses to elaborate--saying it's " still early days. "  The more important reason they're aggressively pursuing GS-7340 is that their blockbuster Viread will go generic in 2017, so a replacement that's even easier to co-formulate with other drugs will help them retain their marketshare--and share price.

JeffJeffRe: NATAP: QUAD-Panel Votes 13-1 To Recommend Approval

Posted by: " Jeton Ademaj "  jeton@...   jetonxxx

Tue May 15, 2012 10:55 pm (PDT),i assume u already know that the Prezista-combo pill will not contain Truvada, as the Viread is being replaced by a new pro-drug of Tenofovir currently labeled " GS7340 " . i also assume u know that Gilead is testing a separate formulation of the elvitegravir- " QUAD " replacing tenofovir with GS7340 (that newer version is in Phase 2 currently).

do u feel that the claims of reduced nephrotoxicity for GS7340 vs Tenofovir r overstated?i gather that norvir + tenofovir is less nephrotoxic than cobicistat + tenofovir......but what i really hoped u n the list might know (or have an opinion on) is whether or not norvir + tenofovir is more or less nephrotoxic than cobicistat + GS7340....

any idea? Jeton

[Guest guest]

You should read the slides in my emails where the recommendations for renal testing are in a slide from gilead, fdaSent from my Verizon Wireless BlackBerryFrom: Jeff <jefftaylorps@...>Sender: Date: Wed, 16 May 2012 07:55:33 -0700< >Subject: Re: NATAP: QUAD-Panel Votes 13-1 To Recommend Approval--Cobicistat issuesHi Jeton--One of the problems with cobicistat is that it makes it hard to measure creatinine levels by artificially raising the blood test measurement--even when more sensitive measures like 24-hr urine collection tell you creatinine levels haven't really changed.  So when you combine it with a drug like tenofovir that can raise creatinine levels, it's hard to know if the usual blood tests are accurate or not.  Definitely a dilemma for clinicians and patients.  In our discussions with Gilead they have refused to offer any suggestions for dealing with this dilemma--leaving it to the FDA to made the determination.   It'll be interesting to see what monitoring recommendations the FDA makes on the label, and what Phase IV post-marketing trials they end up requiring as a requirement of approval.   Naturally Gilead doesn't want to recommend any  onerous and expensive creatinine tests that might be a barrier to people taking their new wonder pill.  We've asked them for years to recommend that all pts starting tenofovir-based regimens get a baseline creatinine level before starting, and have it carefully monitored.  They defer to the expertise of prescribing clinicians--whom as we all know aren't always consistent in their practices or knowledge levels.  Re GS-7340--the supposed advantage of this new tenofovir pro-drug is that it will require a much smaller dose--which is an obvious advantage in co-formulating, and according to Gilead will reduce kidney toxicity.  Though if it results in the same blood levels of TDF (tenofovir dixoproxil fumarate--the active compound) it's unclear why the kidney effects should be any different.  Again, the company refuses to elaborate--saying it's " still early days. "  The more important reason they're aggressively pursuing GS-7340 is that their blockbuster Viread will go generic in 2017, so a replacement that's even easier to co-formulate with other drugs will help them retain their marketshare--and share price.JeffJeffRe: NATAP: QUAD-Panel Votes 13-1 To Recommend ApprovalPosted by: " Jeton Ademaj "  jeton@...   jetonxxxTue May 15, 2012 10:55 pm (PDT),i assume u already know that the Prezista-combo pill will not contain Truvada, as the Viread is being replaced by a new pro-drug of Tenofovir currently labeled " GS7340 " . i also assume u know that Gilead is testing a separate formulation of the elvitegravir- " QUAD " replacing tenofovir with GS7340 (that newer version is in Phase 2 currently).do u feel that the claims of reduced nephrotoxicity for GS7340 vs Tenofovir r overstated?i gather that norvir + tenofovir is less nephrotoxic than cobicistat + tenofovir......but what i really hoped u n the list might know (or have an opinion on) is whether or not norvir + tenofovir is more or less nephrotoxic than cobicistat + GS7340....any idea? Jeton

[Guest guest]

You should read the slides in my emails where the recommendations for renal testing are in a slide from gilead, fdaSent from my Verizon Wireless BlackBerryFrom: Jeff <jefftaylorps@...>Sender: Date: Wed, 16 May 2012 07:55:33 -0700< >Subject: Re: NATAP: QUAD-Panel Votes 13-1 To Recommend Approval--Cobicistat issuesHi Jeton--One of the problems with cobicistat is that it makes it hard to measure creatinine levels by artificially raising the blood test measurement--even when more sensitive measures like 24-hr urine collection tell you creatinine levels haven't really changed.  So when you combine it with a drug like tenofovir that can raise creatinine levels, it's hard to know if the usual blood tests are accurate or not.  Definitely a dilemma for clinicians and patients.  In our discussions with Gilead they have refused to offer any suggestions for dealing with this dilemma--leaving it to the FDA to made the determination.   It'll be interesting to see what monitoring recommendations the FDA makes on the label, and what Phase IV post-marketing trials they end up requiring as a requirement of approval.   Naturally Gilead doesn't want to recommend any  onerous and expensive creatinine tests that might be a barrier to people taking their new wonder pill.  We've asked them for years to recommend that all pts starting tenofovir-based regimens get a baseline creatinine level before starting, and have it carefully monitored.  They defer to the expertise of prescribing clinicians--whom as we all know aren't always consistent in their practices or knowledge levels.  Re GS-7340--the supposed advantage of this new tenofovir pro-drug is that it will require a much smaller dose--which is an obvious advantage in co-formulating, and according to Gilead will reduce kidney toxicity.  Though if it results in the same blood levels of TDF (tenofovir dixoproxil fumarate--the active compound) it's unclear why the kidney effects should be any different.  Again, the company refuses to elaborate--saying it's " still early days. "  The more important reason they're aggressively pursuing GS-7340 is that their blockbuster Viread will go generic in 2017, so a replacement that's even easier to co-formulate with other drugs will help them retain their marketshare--and share price.JeffJeffRe: NATAP: QUAD-Panel Votes 13-1 To Recommend ApprovalPosted by: " Jeton Ademaj "  jeton@...   jetonxxxTue May 15, 2012 10:55 pm (PDT),i assume u already know that the Prezista-combo pill will not contain Truvada, as the Viread is being replaced by a new pro-drug of Tenofovir currently labeled " GS7340 " . i also assume u know that Gilead is testing a separate formulation of the elvitegravir- " QUAD " replacing tenofovir with GS7340 (that newer version is in Phase 2 currently).do u feel that the claims of reduced nephrotoxicity for GS7340 vs Tenofovir r overstated?i gather that norvir + tenofovir is less nephrotoxic than cobicistat + tenofovir......but what i really hoped u n the list might know (or have an opinion on) is whether or not norvir + tenofovir is more or less nephrotoxic than cobicistat + GS7340....any idea? Jeton