Comments on: Vytorin And Zetia For Children? Not Yet, But… http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/ News, Comment and Conversation Fri, 10 Feb 2012 21:02:06 +0000 http://wordpress.org/?v=2.6.2 By: MKM http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215593 MKM Tue, 18 Mar 2008 20:09:49 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215593 I would assume the FDA has some discretion as to whether or not to approve such an application. However, I have not studied the issue and it seems pointless to argue the point. Here is some research comparing ezetimibe with a statin: Landmesser et al., Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans, Circulation. 2005;111:2356-2363. http://www.circ.ahajournals.org/cgi/content/abstract/111/18/2356 Marilyn I would assume the FDA has some discretion as to whether or not to approve such an application. However, I have not studied the issue and it seems pointless to argue the point.

Here is some research comparing ezetimibe with a statin:

Landmesser et al., Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans, Circulation. 2005;111:2356-2363.
http://www.circ.ahajournals.org/cgi/content/abstract/111/18/2356

Marilyn

]]> By: Nathan http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215556 Nathan Tue, 18 Mar 2008 19:23:43 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215556 MKM, I think you are missing the point. So far as I can tell, no one has claimed that ezetimibe is benificial for kids. The only thing we know is that SP and/or Merck has filed for pediatric exclusivity. They are allowed (and encouraged) to do so whether or not the drug is ultimately proved to be benificial for the pediatric population. Filing for pediatric exclusivity DOES NOT mean that the company is claiming that the drug is benificial for the pediatric population. MKM,
I think you are missing the point. So far as I can tell, no one has claimed that ezetimibe is benificial for kids. The only thing we know is that SP and/or Merck has filed for pediatric exclusivity. They are allowed (and encouraged) to do so whether or not the drug is ultimately proved to be benificial for the pediatric population. Filing for pediatric exclusivity DOES NOT mean that the company is claiming that the drug is benificial for the pediatric population.

]]> By: MKM http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215480 MKM Tue, 18 Mar 2008 17:57:22 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215480 Jack2 I don't care whether it lowers LDL in kids or not. I care whether it prevents atherosclerosis, heart attacks and strokes. We don't need ezetimibe for kids with heFH because statins do the job. Witness the patients in ENHANCE, whose arteries were mostly normal, due to having been treated with statins. Given that there is substantial uncertainty with respect to ezetimibe's efficacy, there is no reason to give it to kids, except perhaps in rare cases. Marilyn Jack2

I don’t care whether it lowers LDL in kids or not. I care whether it prevents atherosclerosis, heart attacks and strokes.

We don’t need ezetimibe for kids with heFH because statins do the job. Witness the patients in ENHANCE, whose arteries were mostly normal, due to having been treated with statins.

Given that there is substantial uncertainty with respect to ezetimibe’s efficacy, there is no reason to give it to kids, except perhaps in rare cases.

Marilyn

]]> By: Jack2 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215474 Jack2 Tue, 18 Mar 2008 17:39:06 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215474 Thanks Nathan. MKM: But you didn't know it lowered it in kids. Also, to get pediatric exclusivity the company must pursue a trial similar to the one it pursued to get original market approval - just in a pediatric patients. This trial should not be connected to the Enhance trial. Thanks Nathan.

MKM: But you didn’t know it lowered it in kids. Also, to get pediatric exclusivity the company must pursue a trial similar to the one it pursued to get original market approval - just in a pediatric patients. This trial should not be connected to the Enhance trial.

]]> By: BDM http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215418 BDM Tue, 18 Mar 2008 16:26:32 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215418 The pediatric studies are mandated and conducted under the "Written Request" received from the FDA. They are usually more about safety than efficacy because patients younger than 18 years of age may have age-specific safety concerns and handle the drug differently than older pateints. Hence, safety and pharmacokinetics are very important results coming out of these studies. As a reward for doing the studies, the companies get 6 more months of exclusivity on the market. As they did th studies in HeFH, they may try to obtain an indication for the use of their drugs in this more difficult type of hypercholesterolemia. The pediatric studies are mandated and conducted under the “Written Request” received from the FDA. They are usually more about safety than efficacy because patients younger than 18 years of age may have age-specific safety concerns and handle the drug differently than older pateints. Hence, safety and pharmacokinetics are very important results coming out of these studies. As a reward for doing the studies, the companies get 6 more months of exclusivity on the market. As they did th studies in HeFH, they may try to obtain an indication for the use of their drugs in this more difficult type of hypercholesterolemia.

]]> By: Nathan http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215408 Nathan Tue, 18 Mar 2008 16:12:38 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215408 Jack2, You are correct. The pivotal question is whether the trial has been done in compliance with the FDA request. It has nothing to do with the outcome of the trial. Here's a quote from the FDA web site: (see http://www.fda.gov/cder/pediatric/faqs.htm) "Q9. For approved drugs, must FDA approve a supplemental application before pediatric exclusivity is granted? A9. No. The granting of exclusivity is not connected to approval; the pivotal factor is whether the applicant complied with the terms of the Written Request." Jack2,
You are correct. The pivotal question is whether the trial has been done in compliance with the FDA request. It has nothing to do with the outcome of the trial. Here’s a quote from the FDA web site: (see
http://www.fda.gov/cder/pediatric/faqs.htm)

“Q9. For approved drugs, must FDA approve a supplemental application before pediatric exclusivity is granted?

A9. No. The granting of exclusivity is not connected to approval; the pivotal factor is whether the applicant complied with the terms of the Written Request.”

]]> By: MKM http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215376 MKM Tue, 18 Mar 2008 15:22:02 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215376 Jack2 We know ezetimibe lowers LDL in adults. What we don't know is whether it prevents heart attacks and strokes. Marilyn Jack2

We know ezetimibe lowers LDL in adults. What we don’t know is whether it prevents heart attacks and strokes.

Marilyn

]]> By: Jack2 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215372 Jack2 Tue, 18 Mar 2008 15:18:01 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215372 MKM: I presume they will at least present this data as a poster somewhere (if they haven't already), and probably publish it. For a trial that ends in June 2007 to not be published yet is not unusual. And you're assuming because the drug lowers LDL in kids it will lower it in adults. Probably, but no one knows for sure until they do it. Also, the data will probably better inform dosing in pediatric patients and tolerability expectations. CVMD: So they get exclusivity as long as they do the appropriate trial - not whether the drug works or not. Correct? (that's how I think it should be) MKM: I presume they will at least present this data as a poster somewhere (if they haven’t already), and probably publish it. For a trial that ends in June 2007 to not be published yet is not unusual.

And you’re assuming because the drug lowers LDL in kids it will lower it in adults. Probably, but no one knows for sure until they do it. Also, the data will probably better inform dosing in pediatric patients and tolerability expectations.

CVMD: So they get exclusivity as long as they do the appropriate trial - not whether the drug works or not. Correct? (that’s how I think it should be)

]]> By: MKM http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215256 MKM Tue, 18 Mar 2008 14:24:04 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215256 CV MD: I agree it makes good business sense, but the additional data they generated through conducting a trial in adolescents with heterozygous familial hypercholesterolemia seems worthless. The record on clinicaltrials.gov does not say, but I assume they were only looking at LDL. We already know ezetimibe lowers LDL, so how does that help us? Plus, I have not seen any announcement of the results. It is possible they plan to publish them (the trial was completed in June 2007). Marilyn CV MD: I agree it makes good business sense, but the additional data they generated through conducting a trial in adolescents with heterozygous familial hypercholesterolemia seems worthless. The record on clinicaltrials.gov does not say, but I assume they were only looking at LDL. We already know ezetimibe lowers LDL, so how does that help us? Plus, I have not seen any announcement of the results. It is possible they plan to publish them (the trial was completed in June 2007).

Marilyn

]]> By: CV MD http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215187 CV MD Tue, 18 Mar 2008 13:52:45 +0000 http://www.pharmalot.com/2008/03/vytorin-and-zetia-for-children-the-fda-says-yes/#comment-215187 All this means is that the companies have performed the FDA-required work in pediatric patients and that short-term use is effective and safe for lowering cholesterol. The companies make an agreement with the FDA as to what needs to be done and then they do it. Because they do it, they get 6 months of extra exclusivity for their patent-protected product. It is a program that generates some additional data in kids and makes good business sense. All this means is that the companies have performed the FDA-required work in pediatric patients and that short-term use is effective and safe for lowering cholesterol. The companies make an agreement with the FDA as to what needs to be done and then they do it. Because they do it, they get 6 months of extra exclusivity for their patent-protected product. It is a program that generates some additional data in kids and makes good business sense.

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