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Post by EveningOfTheDay on Dec 2, 2015 1:01:22 GMT -5
FDA approval is practically a rubber stamp for EU approval. I am not sure what you are basing your comment on but I would be extremely surprised if as you say FDA approval a rubber stamp for EU approval. As in many other things European agencies normally demonstrate a healthy degree of skepticism as to what their US based counterparts do and decide. Furthermore, they have their own bureaucratic channels that tend to be more complicated and time consuming than those in the US. I have to recognize that I do not have first hand knowledge on how the process for approval works at the EMA, but one thing I am certain, if it was a clear shot and there were no other considerations Sanofi, obviously, could already have moved on it.
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Post by rrtzmd on Dec 2, 2015 8:52:38 GMT -5
FDA approval is practically a rubber stamp for EU approval. I am not sure what you are basing your comment on but I would be extremely surprised if as you say FDA approval a rubber stamp for EU approval. As in many other things European agencies normally demonstrate a healthy degree of skepticism as to what their US based counterparts do and decide. Furthermore, they have their own bureaucratic channels that tend to be more complicated and time consuming than those in the US. I have to recognize that I do not have first hand knowledge on how the process for approval works at the EMA, but one thing I am certain, if it was a clear shot and there were no other considerations Sanofi, obviously, could already have moved on it. The FDA is generally accepted as the "gold standard" approval body. Offhand, I know of no instance where the EMA has rejected a FDA approved drug. In terms of time required, take, for example, lenvima. Application to FDA was in 2013, while the EMA application was filed in July of 2014. In October of 2014, the FDA moved it to "priority Review Status." In February of 2015, FDA approved it. A month later the EU gave it a "positive" opinion. On June 15, it is approved by the EU and officially launched there that same day. So about five months after the FDA, the EU gave its approval, less than a year after its original EU application. Also bear in mind that simply filing an application doesn't mandate SNY following through on the whole process. At least an attempt at starting to get the ducks lined up, so to speak, would be encouraging. I don't believe the application and review process will be a significant hurdle for afrezza. It's reimbursement that is more likely to be a stumbling block.
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Post by trenddiver on Dec 2, 2015 10:32:53 GMT -5
Everything is falling into place for Sanofi to apply for EU approval. I Don't see any reason not to. The global rollout is like playing Chess. The U.S. pricing is the current benchmark for the rest of the world for Afrezza. The EU tends to have the lowest prices. Middle East would use the U.S. pricing benchmark unless AFREZZA was EU approved and then many countries would use the EU benchmark. Many countries only need FDA approval and SNY can start marketing. The sequence of country's rollout makes a difference in pricing for the world. Obama, I think you are on to something here. Sanofi is obviously taking the long view about pricing knowing that U.S. pricing is very critical in determining the rest of the world pricing, hence the higher U.S. prices for now even though this might be somewhat a negative with U.S. formulary negotiations. Trend
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Post by mnholdem on Dec 2, 2015 10:35:39 GMT -5
Sanofi/MannKind does not want a rubber stamp, IMO. Unlike the FDA label, we want the EMA label to show superiority has been demonstrated. That may involve additional study data, unless the EMA interprets the FDA data differently, which wouldn't be likely.
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Post by lakers on Dec 2, 2015 11:39:32 GMT -5
Sanofi/MannKind does not want a rubber stamp, IMO. Unlike the FDA label, we want the EMA label to show superiority has been demonstrated. That may involve additional study data, unless the EMA interprets the FDA data differently, which wouldn't be likely. Depending on how Sny submits MAA, presents data, and EMA interpretes data, Afrezza can get a better label. Toujeo didn't get better hypo label in U.S. It did in EU. That's why Mnkd needs an old pro as a partner who knows how to play the game. Lower A1c data from Affinity 2 needs to be submitted to EMA and presented in a different light. It's not uncommon to have drugs get different labels in different Territories.
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Post by EveningOfTheDay on Dec 2, 2015 14:02:51 GMT -5
The FDA is generally accepted as the "gold standard" approval body. Offhand, I know of no instance where the EMA has rejected a FDA approved drug. In terms of time required, take, for example, lenvima. Application to FDA was in 2013, while the EMA application was filed in July of 2014. In October of 2014, the FDA moved it to "priority Review Status." In February of 2015, FDA approved it. A month later the EU gave it a "positive" opinion. On June 15, it is approved by the EU and officially launched there that same day. So about five months after the FDA, the EU gave its approval, less than a year after its original EU application. Also bear in mind that simply filing an application doesn't mandate SNY following through on the whole process. At least an attempt at starting to get the ducks lined up, so to speak, would be encouraging. I don't believe the application and review process will be a significant hurdle for afrezza. It's reimbursement that is more likely to be a stumbling block. Here are some examples of dissent between both agencies, 1.- In 2012 Elelyso won approval from regulators in both the US and Israel. The EMA rejected the drug. 2.- Also in 2012 the FDA approved Belviq, yet the EMA recommended against approval, citing potential cardiovascular and central nervous system effects. 3.- Qsymia was also approved by the FDA and rejected by the EMA. 4.- Conversely, while the FDA rejected Lemtrada in 2013, the EMA approved it. I could continue, but examples abound and are easy to find. The real reason for perception to seem to indicate that the EMA follows suit on what the FDA does is simply that the FDA is often the first to receive an application for a drug, has a tendency to approve almost everything they review, and does it considerably quicker and in a more flexible manner than their European counterpart. Furthermore, due to its own nature, the European Union agencies tend to have a much more complex estructure that accounts for collaboration between all country members, which makes EMA decisions rather more complex and slow. This possibly being one of the main reasons drugs tend to be submitted to the FDA first. So I will say it again, I do not think the EMA sees the FDAs approval as a rubber stamp on any drugs. I am as certain as I can be that Sanofi clearly understands both regulatory bodies and what it takes to get a drug approved. It was MNKD, not Sanofi that took the care of putting Afrezza through approval in the US. My guess is that on the one side, having received two delays, there was a considerable perceived risk, but also it is likely that MNKD realized that going through approval would put then in a considerably better negotiating position. Sanofi will get the drug approved in Europe in 2016 and in Japan in 2017, as stated in their plan, they clearly understand the time frame involved, but likely there are other consideration like improvements to label or dosing guidance that should be at play here. IMO
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Post by bradleysbest on Dec 2, 2015 14:07:06 GMT -5
This year (2015) for EU & 2016 for Japan?
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Post by EveningOfTheDay on Dec 2, 2015 14:12:37 GMT -5
This year (2015) for EU & 2016 for Japan? Sorry Bradley. I corrected that. This year has been so lousy that I guess I am a bit too eager for 2016 to be here already, so I jumped gun on that one.
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Post by dreamboatcruise on Dec 2, 2015 14:29:14 GMT -5
Sanofi/MannKind does not want a rubber stamp, IMO. Unlike the FDA label, we want the EMA label to show superiority has been demonstrated. That may involve additional study data, unless the EMA interprets the FDA data differently, which wouldn't be likely. Depending on how Sny submits MAA, presents data, and EMA interpretes data, Afrezza can get a better label. Toujeo didn't get better hypo label in U.S. It did in EU. That's why Mnkd needs an old pro as a partner who knows how to play the game. Lower A1c data from Affinity 2 needs to be submitted to EMA and presented in a different light. It's not uncommon to have drugs get different labels in different Territories. That would be an amazing outcome if it happens. I would repent for every unkind thought I've had regarding Sanofi. I hope you are correct about that possibility.
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Post by brianrocco on Dec 3, 2015 8:18:32 GMT -5
Hakan Edstrom referred to the above referenced studies at the beginning of his 11/9/15 conference call. He stated that for the first study the treatment of subjects had been completed and the "data analysis and clinical study report is tracking ahead of FDA-assigned due date." For the second study, the subjects will have completed dosing by early December. These studies deal with the "effectiveness" of Afrezza in terms of PK and PD. While the PK (absorption of insulin by time) has been publicized and charted by Mannkind 10k's and Afrezzauser.com (Blog, week 15), the PD (glucose infusion rate) has been questioned. (www.acessdata.fda.gov "Afrezza pharmacokinetic study" pages 15-16.) My understanding of the biochemical processes and of clinical trial reporting procedures are both nil and I could be missing important aspects of both. But I see the above as leading -- hopefully very quickly -- to selling Afrezza on its effectiveness in blood sugar control, not just its "convenience" and needle avoidance. Does someone have insight regarding: 1) When the results of the above studies will be available to the public? 2) If the Afrezza PD mimics the Afrezza PK which mimics the effects of a healthy pancreas, could these studies result in the ability of Sanofi to immediately promote Afrezza on its effectiveness in blood sugar control? Thanks.
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Post by rrtzmd on Dec 3, 2015 11:04:50 GMT -5
Hakan Edstrom referred to the above referenced studies at the beginning of his 11/9/15 conference call. He stated that for the first study the treatment of subjects had been completed and the "data analysis and clinical study report is tracking ahead of FDA-assigned due date." For the second study, the subjects will have completed dosing by early December. These studies deal with the "effectiveness" of Afrezza in terms of PK and PD. While the PK (absorption of insulin by time) has been publicized and charted by Mannkind 10k's and Afrezzauser.com (Blog, week 15), the PD (glucose infusion rate) has been questioned. (www.acessdata.fda.gov "Afrezza pharmacokinetic study" pages 15-16.) My understanding of the biochemical processes and of clinical trial reporting procedures are both nil and I could be missing important aspects of both. But I see the above as leading -- hopefully very quickly -- to selling Afrezza on its effectiveness in blood sugar control, not just its "convenience" and needle avoidance. Does someone have insight regarding: 1) When the results of the above studies will be available to the public? 2) If the Afrezza PD mimics the Afrezza PK which mimics the effects of a healthy pancreas, could these studies result in the ability of Sanofi to immediately promote Afrezza on its effectiveness in blood sugar control? Thanks. "When the results of the above studies will be available to the public? " Whenever SNY decides to release them. The results belong to them and it's up to them to release the results. SNY does not have a good history of releasing results. "...could these studies result in the ability of Sanofi to immediately promote Afrezza on its effectiveness in blood sugar control?" No. The two studies were mandated by the FDA to clarify dose/response issues. For example, when MNKD did the PK/PD studies they compared 4U and other doses of afrezza to just a 8 or 10U dose of lispro. So one of the new studies will now compare equivalent doses -- 4U afrezza versus 4U lispro, etc. The other study is to assess "Within-Subject Variability of a Single Dose of Afrezza." If you look at the PK graph shown in the afrezza insert, you can see that the insulin concentration after dosing shows a wide range of variability as compared to lispro. Why is that? What is even more odd is that the PD graph implies that there is no difference in the time of onset of effect or in the the glucose lowering effect for about the first hour between afrezza and lispro. As I recall, SNY even included a comment on the graph or just below it noting that oddity. Why doesn't afrezza's PD graph reflect its PK graph more than it does? In any case, to truly prove afrezza is more than non-inferior will likely require a large, "real life" trial like the one SNY is doing for toujeo.
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Post by longinvstr on Dec 3, 2015 11:42:19 GMT -5
In any case, to truly prove afrezza is more than non-inferior will likely require a large, "real life" trial like the one SNY is doing for toujeo. Good thing, then, that the First Amendment protects drug companies too. If the preponderance of the evidence (not just FDA trial evidence) supports the claim, the claim may be made. Thank goodness "proof" exists outside of government constructed/regulated proving grounds
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