More evidence of a shift in the winds at FDA, here. . . .

[UPDATED 04.2830.08 AM -- Another very-well researched, and well-written piece (from that shiny-new pen of PM, at Gooznews) on the changing tides at FDA. . . .

4.28.08: As will, no doubt, be the case, repeatedly, in the future, Pharmalot is on this, now -- and he's done a bang-up job of making it easy to read, and yet coveying all the essence of it. . . Kudos!

And, from the very same friend of this blog as below -- this would seem to confirm all of the below.]

This just in, from a friend of this blog (Thanks!) — and, as additional evidence of an emerging trend toward more rigorous review-before-approval at FDA — I’ve been alerted to the fact that FDA told Isis and Genzyme that they will need to conduct a study with clinical endpoints before FDA will even consider approval¹. The drug is Mipomersen (formerly Isis 301012). This is plainly significant, because the companies clearly had been hoping to get approval based on LDL-lowering alone. I think this reflects new thinking at FDA on clinical v. surrogate endpoints — and that, in turn, sounds a lot like FDA has learned some “hard lessons” from the ENHANCE study train-wreck.

From the Genzyme Form 8-K, of April 23, 2008:

. . . .Mipomersen for high-risk cardiovascular disease

Genzyme expects to finalize its license of mipomersen from Isis Pharmaceuticals in the second quarter and subsequently communicate a development plan for the product. Mipomersen is a lipid-lowering agent being developed primarily for patients at significant cardiovascular risk who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins. The product offers an innovative approach to addressing a serious unmet medical need, and Genzyme believes it could prove to be the most effective lipid-lowering agent for high risk cardiovascular disease patients for whom conventional therapies are not sufficient. The product may provide significant benefit over the standard of care and targets a well-defined and severely ill patient population. Mipomersen is currently being studied in a Phase 3 clinical trial involving patients with homozygous familial hypercholesterolemia. . . .

~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: This FDA directive does not affect the accelerated approval track of the drug, for homozygous familial hypercholesterolemia patients.]

More evidence of a shift in the winds at FDA, here. . . .

[UPDATED 04.2830.08 AM -- Another very-well researched, and well-written piece (from that shiny-new pen of PM, at Gooznews) on the changing tides at FDA. . . .

4.28.08: As will, no doubt, be the case, repeatedly, in the future, Pharmalot is on this, now -- and he's done a bang-up job of making it easy to read, and yet coveying all the essence of it. . . Kudos!

And, from the very same friend of this blog as below -- this would seem to confirm all of the below.]

This just in, from a friend of this blog (Thanks!) — and, as additional evidence of an emerging trend toward more rigorous review-before-approval at FDA — I’ve been alerted to the fact that FDA told Isis and Genzyme that they will need to conduct a study with clinical endpoints before FDA will even consider approval¹. The drug is Mipomersen (formerly Isis 301012). This is plainly significant, because the companies clearly had been hoping to get approval based on LDL-lowering alone. I think this reflects new thinking at FDA on clinical v. surrogate endpoints — and that, in turn, sounds a lot like FDA has learned some “hard lessons” from the ENHANCE study train-wreck.

From the Genzyme Form 8-K, of April 23, 2008:

. . . .Mipomersen for high-risk cardiovascular disease

Genzyme expects to finalize its license of mipomersen from Isis Pharmaceuticals in the second quarter and subsequently communicate a development plan for the product. Mipomersen is a lipid-lowering agent being developed primarily for patients at significant cardiovascular risk who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins. The product offers an innovative approach to addressing a serious unmet medical need, and Genzyme believes it could prove to be the most effective lipid-lowering agent for high risk cardiovascular disease patients for whom conventional therapies are not sufficient. The product may provide significant benefit over the standard of care and targets a well-defined and severely ill patient population. Mipomersen is currently being studied in a Phase 3 clinical trial involving patients with homozygous familial hypercholesterolemia. . . .

~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: This FDA directive does not affect the accelerated approval track of the drug, for homozygous familial hypercholesterolemia patients.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]

More evidence of a shift in the winds at FDA, here. . . .

[UPDATED 04.2830.08 AM -- Another very-well researched, and well-written piece (from that shiny-new pen of PM, at Gooznews) on the changing tides at FDA. . . .

4.28.08: As will, no doubt, be the case, repeatedly, in the future, Pharmalot is on this, now -- and he's done a bang-up job of making it easy to read, and yet coveying all the essence of it. . . Kudos!

And, from the very same friend of this blog as below -- this would seem to confirm all of the below.]

This just in, from a friend of this blog (Thanks!) — and, as additional evidence of an emerging trend toward more rigorous review-before-approval at FDA — I’ve been alerted to the fact that FDA told Isis and Genzyme that they will need to conduct a study with clinical endpoints before FDA will even consider approval¹. The drug is Mipomersen (formerly Isis 301012). This is plainly significant, because the companies clearly had been hoping to get approval based on LDL-lowering alone. I think this reflects new thinking at FDA on clinical v. surrogate endpoints — and that, in turn, sounds a lot like FDA has learned some “hard lessons” from the ENHANCE study train-wreck.

From the Genzyme Form 8-K, of April 23, 2008:

. . . .Mipomersen for high-risk cardiovascular disease

Genzyme expects to finalize its license of mipomersen from Isis Pharmaceuticals in the second quarter and subsequently communicate a development plan for the product. Mipomersen is a lipid-lowering agent being developed primarily for patients at significant cardiovascular risk who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins. The product offers an innovative approach to addressing a serious unmet medical need, and Genzyme believes it could prove to be the most effective lipid-lowering agent for high risk cardiovascular disease patients for whom conventional therapies are not sufficient. The product may provide significant benefit over the standard of care and targets a well-defined and severely ill patient population. Mipomersen is currently being studied in a Phase 3 clinical trial involving patients with homozygous familial hypercholesterolemia. . . .

~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: This FDA directive does not affect the accelerated approval track of the drug, for homozygous familial hypercholesterolemia patients.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]

Probably this wasn’t ever going to "move the needle" very much at Schering, but. . . .

. . . .this is plainly a disappointment for the Fred Hassan/Schering-Plough strategy of taking older, mature-market drugs, and re-igniting them by combining them with another active agent. [Think of Vytorin's marrying of Zocor with Zetia, here.] While the company said it was “evaluating its response” to the non-approvable letter from FDA, it probably means a[nother] write-off of at least $50 million in development costs, ad pitch consulting and strategy materials, etc. associated with the combo’s one-and-one-half-year journey from FDA submission (August 2007), to last night.

I wonder whether the letter is also a harbinger of things to come at FDA: is this the beginning of a new — more skeptical — FDA review and approval process, when the clinical benefits of these combos appear marginal (as compared to taking the two drugs as two separate footballs), but the protections against patent-expiry, or generic incursions, seem to be one of the company’s main motivating factors for submitting an ANDA?

I think it likely. Of course, Pharmalot’s Ed Silverman has an even wider, and more cogent, meta-narrative he points us to, this morning — and I think he is largely right. Brilliant, that one (though, Ed, isn’t photocopying US currency, at least theoretically. . . . still a Class B felony? Heh!).

I do think, insofar as meta-narratives go, this is additional proof¹ that the pendulum at FDA is swinging toward “slow to approve/quick to issue warning letters” — [as to Schering, then, think about a slower path for its Sugammadex product, even though it holds an FDA "approvable" letter, at the moment -- it is not yet "FDA approved"] and thus, relatively-speaking, away from where it had been for a good portion of the two Bush/Cheney administrations.

~~~~~~~~~~~~~~~~~~~~~~~~~

[Footnote 1: I'll note in passing that FDA drug unit chief Woodcock, and Baxter CEO Bob Parkinson, will appear before a Congressional Committee, at a hearing provocatively-entitled "The Heparin Disaster: Chinese Counterfeits and American Failures", on this coming Tuesday, to explain how it was that, between FDA inspections of the wrong Chinese supply-plants, and Baxter's filling and packaging operations (in reliance on various global suppliers, of course) -- the batches of Heparin (both the Baxter-versions, and the competitors' versions) got contaminated, in the first place, shipped into hospitals, in the second place, and injected (or dripped) into the IV lines of patients, in the final analysis. Which is to say, I think it likely that the legislative/investigatory pressures from Sen. Grassley, and Reps. Dingell and Stupak, will not abate -- and FDA is adjusting its course, accordingly.]