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I don't see any confusion or obfuscation in Schlomo's statement... it's very straight forward:
Actually, the statement is not straight-forward. Either the language was specifically and carefully chosen, or he was just speaking off the cuff and was not so precise with his language.
From the cynical (and usual Teva approach) the language really says nothing about what the FDA thinks of the application. Instead it says what TEVA thinks of their drug, and their inference as to why it is now moving to OBP.
From the usual conversational perspective, we would assume he is talking about the FDA told us we have achieved chemical sameness, so were done here, just need to move it on for immunogencity to OBP and then we are good.
Again, if the drug is only now being examined for immunogenicity, why was it not being examined for this long ago? Momenta's drug was well over a year ago. If you look at the evidence, Teva is not straight-shooting but rather talking from the hip to keep up the optimism and progress being made.
But that is where it is at, and all we can do is parse and interpret and look at all the evidence. We cannot really know at this point in time, we can just suspect.
Did Teva actually repeat that statement word for word? If so, then it is likely an intentional use of wording.
The question needs to be posed to them "Did the FDA specifically tell you that your lovenox drug has been found by the FDA to be chemically the same so that it is ready for approval once the immunogencity issues are examined or is that a conclusion that you have come to on your own from other evidence, and if so, what other evidence?"
A compound question, which should be broken into two questions, but that is really what needs to be asked to clarify this issue.
Tinker
I don't know what is going on here, but it occurs to me if Teva was in "labelling" discussion a year ago, and this was well over a year after the immunogenicity concerns were raised by the FDA to begin with, then WHAT THE HECK is Teva's drug doing back being evaluated for immunogenicity issues? Should that not have been done prior to "labelling" discussions? I mean, no drug would even get that far without these immunogenicity concerns addressed.
Also, as we discussed way back then, there are no labelling issues around a substitutable generic, it takes the label of the innovator drug because that is what it substitutes for.
No, this does not add up. Doesn't mean Teva might not have the real goods this time, but if this is what Teva is saying, the rhetoric is pure B.S.
Tinker
This sentence sure reads to me that Teva believes it has met the 5 criteria. Yet you say:
Here is Teva's comment after MNTA's approval:
After reviewing the FDA's response to the citizen petition, which outlines 5 criteria to demonstrate "sameness", Teva believes that it has demonstrated to the FDA that its version of generic Lovenox meets their criteria and that Teva's pending ANDA is approvable.
Teva maintains the approval for an ANDA for generic Lovenox is appropriate because:
- The active ingredient in enoxaparin is significantly better characterized than the active ingredients of significantly more complex molecules
- Pharmacologically active portions of enoxaparin can be identified and replicated, and
- In vitro and in vivo PD tests are rapidly indicative of drug efficacy and safety
suing in India is would not be useful.
Well, the cat is out of the bag. The product Teva is trying to pass off to the FDA as a generic copy of Lovenox was developed by ItalFarmaco and is manufactured by ItalFarmaco. It’s the same product Lupin sells in India under the brand name, Lupenox (#msg-56014815). Teva’s contribution is limited to FDA regulatory submissions and prospective US distribution.
<<<was that MNTA pretty much wrote (established?) the approvability standard for the FDA for generic lovenox>>>
I kind of pretty much surmised that. Sometimes we are told to only listen to what people say without examining the underlying inferences and realities that go with it. In this case, it was pretty clear that MNTA drafted the standards and the the FDA (wisely) took credit for it.
One thing that also struck me was the wording of Teva's press release after MNTA lovenox was approved in how diced and legalese and specific it was in the way that it exactly avoided stating that it met the standard as expounded by the FDA. When one reads language like that, one either has to conclude that an inarticulate pin head wrote it, or the inanity of it was intentional, and to serve a particular purpose.
In this case to scare the analyst community that Teva was on MNTA's heels, and at the same time CYA (ie, cover themselves from stating an out and out actionable and misleading thing).
There have been many clues like this. We shall see if it holds up. I think Dew's perception on this is looking more and more correct. It is just going to take us some time to see it play out. If not Teva, then who? Well, no one. Even the folks at MNTA don't really, really, really know, or they'd be buying shares hand over fist, insider tax selling or not. Even they cannot know. Although they do indeed suspect.
Tinker
This FDA response is utter B.S. At a minimum, why did they not ask for the QT data 6 months ago with their first response letter? Bydureon is a great drug, without question. It is expected to be used by millions of people, probably for years at a time (so the need for caution) but this seems over the top to me.
Tinker
Suggest you, like jmkobers, might want to move on wrt to a 2 year old semantics argument about whether a drug with very probable good efficacy that failed due to safety is a scam?
I am hardly a person with in-depth drug experience. However, I did a simple Google search on the class of drugs this drug from RPRX was because it hit me as odd as to how quickly RPRX was moving the drug forward, and how small the clinical trials (and few) the clinical trials were in comparison to those being done on elabolix by NBIX.
It did not make any sense, particularly with the type of drug RPRX was testing they the could move their drug through clinical trials with smaller trials, and fewer trials, and somehow get to market that way when NBIX could not.
It looked like a scam even to me, without any specialty knowledge. In fact, it did not take much to figure it out.
So I suggest you rexamine your comparative comments in regard.
Tinker
P.S. A nice triple on MNTA - which most people ignored happened. The recent price retreat is more difficult to understand, but needs to be re-examined from the current facts. And I am not making any comment on those, but just primarily in regard to RPRX and that yes, indeed, MNTA was a nice triple for those cynics who pop up from time to time with little appreciation of that fact.
<<<If so, how can one find from the jury pool enough people who are skilled enough to understand what they're hearing yet not such biotech junkies, like us, that they're biased?
Is it simply up to the attorneys to select jurors who they deem to have intelligence to which they can speak to?>>>
Intelligence has nothing to do with it. The jury simply needs to find specific facts. The jury does not need to understand the science beyond how the attorneys will educate the jurors about through their experts. Happens all the time.
<<<Finally, has MNTA/Sandoz tipped its hand for the denied summary judgement to the extent that their cards are now firmly on the table for Teva's benefit? (i.e., Does Teva now have a strategic, if not tactical, advantage for trial?)>>>
No. By the time a case like this goes to trial, both sides already know all the evidence that is going to be submitted. There are no cards left to hold. You put your case out there, and you respond to their case. Kind of like an NFL football team. There are no surprises, you know everything there is to know about the other side, it is a matter of execution and responding on the fly to things that may go differently than expected.
Tinker
<<<The problem with your (mis)reasoning here is your implication that the judge's ruling on the TRO has any direct relevance to the issues Sanofi is raising before the court.>>>
It does have direct relevance as Sanofi claims the drug is dangerous. You don't let a drug that you are so sure of being dangerous on the market, at least without a fight. So the point is, is that the court is not going to be ruling on the basis of whether or not this drug is dangerous. That is off the table, and Sanofi is arguing the much narrower, technical point, no matter what their attorneys may claim in an article, like the one that was posted earlier, which made the claim that Sanofi thinks the drug is dangerous, yet did not seek a TRO.
Not seeking the TRO and an imminent danger to the public are not consistent. Sanofi therefore is not credibly making any argument of danger, and instead their issue is relying on the narrow technical argument that a drug that is not dangerous can still not be approved in the manner that the FDA approved it, because the statute says so - and some future drug, if approved in this manner, might be dangerous, because this drug in front of the court is not, or at least we have no evidence that can prove it is dangerous (which is why we consented out of the initial TRO before 10,000s of thousands of patients started to receive the drug in life threatening situations).
If I must say so in one of the more convoluted sentences that I've authored recently.
Tinker
<<<because no judge in America would overrule the FDA on whether a drug is safe or not before said drug ever reaches the market.>>>
There is absolutely no reason for a TRO in this case absent the protection of the public. If a drug laced with cyanide is approved by the FDA the judge is not going to wait until it is distributed to tens of thousands of patients. The judge is going to protect the public and stop the distribution of the drug until the matter can be sorted out.
The innovator is going to do the same.
In this case, the innovator consented to not pursuing the TRO for a drug that it calls "dangerous" so that tens of thousands of patients can be victims of this dangerous generic medication. If a real and substantive safety concern is the issue, you pursue the TRO with great urgency, and not as a litigation tactic. Sanofi has lost any argument it has on this issue absent to something happening in the real world.
I come across issues like this all the time in the courtroom. Not as drug attorney but in my field of practice (which has nothing to do with IP or commercial litigation (although I use to conduct commercial litigation). The fact is, if things were so bad you would have sought the remedy to fix the problem up-front, or things simply were not so bad.
In this case, the actions speak for themselves. Neither the judge, the FDA, nor Sanofi think this generic is dangerous.
As for the statutory interpretation, that is another matter.
Tinker
One other comment about Sanofi's position, at least as it relates to the cited article, in which the article cites Sanofi as stating that it is not possible to fully characterize the drug molecule by molecule. First, this position is very bullish for MNTA who can do this better than anyone else, and in fact claims that they have.
Second, if the judge rules for Sanofi (despite already tacitly admitting, and Sanofi doing the same) that m-enoxparin is not dangerous (and danger also means does not work as represented) the court will be setting a standard that is so high that no one will be able to create generic biological drugs. And the court is simply not going to do this. A generic has never had to copy molecule by molecule the innovator product, and the same will be true here.
But Sanofi's position is the one that MNTA would be taking if Teva's product were accepted on lessor characterization than MNTA managed, except without the immunogenicity issue.
MNTA would have a better case on this score than Sanofi does on its present count. I am not making any opinion that MNTA would so sue the FDA on this ground, or that it would even have the grounds to do so. Just using it as comparison to better illustrate the Sanofi case and what it may mean.
Tinker
<<<I suppose it is technically inaccurate to say Sanofi did not seek a TRO but for all intents and purposes, in the telephonic status conference, they abandoned the request>>>
Which is the equivalent of Sanofi admitting the generic is not a danger to the public. 10,000 or more scripts since its been put on the market and no issues (I'm just using this as an example number, but more than 10,000 have had to have issued and been used to date - as I don't know the actual number) speaks bold and loud to any argument that the drug is dangerous.
I think Sanofi keeps putting the issue out there as PR and marketing material, and not for its legal case.
Its legal case really comes down to (1) irreparable harm, and (2) the FDA violated its statutory authority when it asked for immunogenicity information.
So it comes down to, does the FDA have the power to collect some information to insure manufacturing quality or does it not. I'm not going to hazard a guess other than to say, yes, that is a very narrow reading of the statute that Sanofi is trying to make, and unless the FDA is using the manufacturing rationale as a pre-text, it does not sound like a very plausible ruling to read the statute the way that Sanofi is requesting - at least from a Congressional intent, and practical real world perspective. Perhaps the judge prefers just to stay within the parameters of the specific and narrow text (which is not usual in matters like this, but not unheard of).
And as Dew presciently pointed out multiple times, with lovenox, where immunogenicity is not a great problem, there is little reason to do it other than to examine the manufacturing process. Given the 2008 heparin scare, the FDA could order Sanofi to test the immunogencity of its own product to insure the quality of its manufacturing process if the FDA had doubt about it.
Tinker
<<<Because Sanofi did not immediately seek a temporary restraining order to halt shipments of generic Lovenox, the product is now on the market pending a ruling on the preliminary injunction.>>>
How about because we on this board know more about the situation then these professional journalists who cannot get one story correct.
The immediately TRO was denied. Thank you.
Which, btw/ also indicates that the judge does not buy that generic lovenox is a danger to the public argument. Imagine denying a TRO when you know the result is tens of thousands of patients receiving the generic. The judge's ruling indicates that he does not consider this generic to be a danger of any kind as the public danger would be extraordinary if he had any doubt about it.
Whether or not the judge sides with Sanofi's statutory argument is something else and a technical reading of the statute, but it won't be because he considers the process botched or the drug dangerous.
Tinker
Given that since this generic market is so different from practically any other that we are in somewhat new territory here. This said, under any scenario, if MNTA remains the sole generic they will make hundreds of millions per year gross income. Whether they get 80%, 50%, or 30% market share.
If Teva is approved, this market will almost certainly revert to the more typical model as Sanofi will not want to fight two companies in a price war, and will instead profit maximize, unless the 3 players can "signal" each other into each reaching profit maximizing market share points. In such case, the generics will almost certainly hold greater than 50% marketshare.
So we can fuss over it all we want, but that is the certain outcome in the sole generic, and the very likely outcome in the 2 generic outcome.
At the current share price, any of these outcomes are good for MNTA, with the former being a multi-bagger pre-copaxone.
Tinker
<<<Is Sandoz winning the battle with largest pharmacy managers, Medco, Kaiser etc>>>
You gotta stay on top of the board. MEDCO has already put out notice of a generic lovenox to its members. That was a few days ago.
Tinker
http://economics.about.com/od/unitedstates/l/aagenericdrugs.htm
Bladerunner, do your own reading on the economics of generic drug markets. Either Sanofi will do what it and its peers have always done, or they won't. What they have always done is raise their prices and let the generics fight it out below.
And before you get to it, this is not a usual generic market. Lovenox will not have many generic entrants,and TEVA's entrance is not at all ensured at all. So read it in the context of this first time, unique, generic, not the run of the mill small molecule generic as studied by this article.
Afterwards, you can decide for yourself if Sanofi will get into a price war or do what it always has done. That is up to Sanofi.
Tinker
it is a hugely inefficient price. either our board has it wrong BIG TIME or the market will send MNTA significantly higher (in the near future).
Or both. Remember Provenge from DNDN, hey, Tysabri from ELN. I remember VRTX crashing into the low teens on bogus news reports on telaprevir. If I remember correctly it involved quotes from an unnamed "intern" citing the virtues of boceprevir but how fearful he was of telaprevir and how it needed more testing, etc. It was blatantly false, yet, the price moved from $30 to $14. I got a quick double out of it. But the price move was so swift it was scary, to say the least. Yet no substance at all to it.
MNTA is a bit more ambiguous. The Teva threat is certainly real, the litigation is certainly real. The insider selling is certainly real (but expected). But all in all, run the numbers, let me know if the market is not divorcing reality from the share price. Happens all the time when there is complex news. Sometimes it is easier or harder to see through it to the truth, but sometimes the price falls far enough that it doesn't matter, even if the worse happens.
That appears to be the case now (except for the litigation issue that could prove catastrophic, but the risk is low). Teva is not catastrophic, although it will be a spoil sport if they somehow manage to get an identical approval by the FDA for a product that is not fully characterized, but nevertheless deemed good enough.
MNTA managementthinks it is unlikely (or not possible actually) for Teva to gain such approval without full characterization. From their press release immediately following MNTA's approval, we do know that Teva has still not fully characterized the drug, and is still holding to the same line it has for quite some time. But maybe they'll go beyond that and pull it off somehow, who knows. But the share price pretty much already reflects that.
Tinker
Thanks ThomasS,
I do remember that conversation now but just dismissed it as hopeful thinking. But the use of language such as in "label discussions" for a CEO who specializes in generic approvals, maybe more than just hopeful thinking. I don't know if it involves a branded generic label, but I do get the feeling that Teva continues to try and convince the FDA that the criteria they are demanding is overkill and not necessary. That Teva's drug meets all the requirements that the FDA should reasonably have, and that such discussions continue to be on-going.
I get the same impression from the recent releases that Teva gave, as they stick to the same line even after the FDA announced their criteria.
Not enough information to put money down on, but interesting speculation to say the least, and not at all out of the question as to what was meant by the comment, by a person who should be very familiar with the process and language of generics.
Tinker
ThomasS,
That is a very interesting interpretation. I've owned MNTA since the last time it was in the mid single digits (was that 9 months or 18 months ago, I don't remember) but have only followed it intently from time to time. I don't recall the discussion of the FDA/Teva labeling discussions that happened approximately 6 months ago. Can you refresh my recollection on this press release by Teva?
That would be very interesting.
Thanks if it is not too much trouble.
Tinker
<<<Until recently, U.S. regulations prevented the creation of this type of biogeneric medicine>>>
Here is one error, since it was not regulated as a biogeneric.
Tinker
Dew,
Having just come across this January post on Teva's comments, this would seem to answer the questions we have if Teva has somehow submitted a new drug or revised their old drug using better characterization. Obviously, they have not.
What I also find bullish here is that Teva is stating in January that their full immunogenicity testing results were submitted no later than January of 2010. And yet you still have Teva speculating that since they submitted their data a month after MNTA, that perhaps the delay of obtaining approval is that the FDA has had one last month to review this data.
Come on, it is August for crying out loud!. It has been at least 8 months, and 9 months for MNTA. That seems to be about as fecetious of reasoning as any I can think of.
I believe the historic Premarin example set the stage, and the FDA monograph, both in summary and in detail, closed the curtain on Teva's theory that it only need to replicate the "active sequence". The active sequence in Premarin was also found by companies who spent tons of money to do it. But they never were able to reproduce the other contituent chains that altered the efficacy of the drug in ways that no one exactly knew how (as it was never tested) but they knew they did something.
MNTA gets around all this by reproducing these strands, so they don't have to argue that strand x or strand y or "inactive".
The Premarin example is very illustrative as the estrogen itself, thought of as the "active" component turned out to be regulated by all these other constituent chains. And that is exactly what the FDA is saying now, that the active heparin chains are great, but their characteristics in the way that they behave in the body is dependent upon these other component chains.
At least that is my interpretation of what the FDA has said, and this is in direct contradiction to what Teva has been claiming and lobbying to make the standard.
Tinker
<<<Teva's problem is more than just the ability to fully characterize the components of Lovenox. They would also need to identically manufacture. This must also be part of MNTA's proprietary toolset: the ability to reverse engineer Lovenox.>>>
I agree, and we know when they filed their ANDA they had not characterized the molecule sufficiently to meet the criteria the FDA put out.
This being the case, I don't believe that Teva could just rejigger the drug over time with the same ANDA as they came to understand more of it. Instead, all they can do is take their originally submitted drug, go through it, and more carefully characterize their drug in comparison to Lovenox, and convince the FDA that it is good enough.
As we have discussed, a new ANDA filing after mid 2008 would be confidential. I think only by filing a new drug that is fully characterized can Teva meet the standard. Their original drug just cannot match Lovenox due to the lack of characterization and the astronomical odds of accurately reproducing and reverse engineering the drug without substantial characterization of the drug to begin with.
That is my line, and I'm sticking to it. I just don't see anyway around it if Teva is sticking with its original drug, and its original drug cannot be reformulated in the same ANDA filing. Which rules out most everything except for some double secret subsequent ANDA filing - which would be possible I guess, but would seem incredulous if true. I would think TEVA would want the world to know that they to have MNTA type powers. Would add more value to the company.
Given that analysts have stuck with the same Teva line, and they get the line from Teva, it would seem the conclusion from all the information given us that Teva has not submitted some double secret new ANDA on a more fully characterized candidate T-enoxparin II.
Tinker
Detailed analytical information on Premarin's composition is the necessary basis for adequate characterization of the product. Obtaining this information is feasible. The constituents of Premarin are small molecules that can be fully characterized by analytical chemistry, unlike the macromolecular constituents of most biological products, which are difficult to fully characterize due to biologic variability. It is desirable that the components present in Premarin at or above 0.1% be characterized and their biological activities determined.
It has been argued that DHES cannot be considered an active ingredient of Premarin because its presence in and percent composition of the formulation are not specifically controlled during the manufacturing process. Wyeth-Ayerst has submitted data demonstrating that DHES is present at about 4.4% of label claim with a range of 4.0 to 5% (based on ten lots of 0.625 mg Premarin tablets). It is desirable that any active ingredients, once identified, be controlled during the manufacturing process.
I think this is the key passage from the Premarin release from the FDA. MNTA has shown what is possible. No other company could do this back in Premarin's day (although the FDA declares here that it was possible). Given this, I don't see why the FDA would require any less now, particularly since MNTA has proven that it is possible.
So I think what we are left with is can Teva characterize in this manner? The answer from all the available sources is no.
What we don't know if Teva has, although this would be a long shot, submitted a new application with some acquired or developed technology that they picked up along the way. However, I think this is even a bigger long-shot because brokers and analysts have not been given any information, at all, at to Teva's capacity to fully characterize. They are still under the belief that Teva is still working with what it was working with pre-patent invalidation.
Anyways, food for thought. We will see when we see.
Tinker
Thanks Dew.
Also, I assume then if Teva withdrew their initial ANDA that this would also now be privileged post patent invalidation.
Just looking into every crack we can find.
Tinker
<<<If Teva were to submit a new ANDA predicated on a reformulation, investors would not necessarily find out. The FDA would not disclose such an action; Teva might or might not disclose it.>>>
Then how could a citizen petition be filed in regard to the new ANDA? I am not familiar with this area of law, but to have the right to submit a citizen petition, the citizen would have to have a means to identify when a new ANDA is filed so they could analyze it and submit a petition.
At least I'd think you'd have to give notice at least on this basis. But maybe that would not be so. If that is not so, then it is clear how Teva could turn the tables around. Simply recharacterize the drug with more state of the art techniques that they may have developed or acquired over the years, and submit the newly derived and better characterized drug. We might not then, even be talking about their original drug that Teva discussed in their 2004 letter. For all we know they may have recharacterized and resubmitted back in 2007.
Thanks for anyone who might have information on this.
Tinker
I don't believe that the look of the drug from the packaging and injection proves any point other than it is packaged similarly.
What I do find interesting is how the goal posts have moved.
From Duethsche Bank analyst coverage, September 18, 2009 (as an example): "We believe comments from the FDA suggest that if a generic uses the same starting product as the brand, complete characterization may not be required. In addition, we believe Xa:IIa activity assays will be sufficient to prove therapeutic equivalence." They therefore believed that multiple generics would be approved in 2010. We see the fair valuation under this scenario as $18/share."
If this were the case Teva's product would already be approved, and the FDA would not make activity assays part 4 of 5 requirements.
I actually do not like some of the euphoria that some are sounding here, such as MNTA is a "sure thing, or as close as it comes." Once people think that, the investment has peaked.
Fortunately there is still much fear, uncertainty, and doubt here despite the fact that the FDA has spoken and created a very stringent criteria for approval. A criteria necessary because for a generic to be equivalent in a complex product like lovenox, it has to have the same predictable and understood characteristics.
A doctor cannot order the usual lovenox prescription and then have the generic behave differently in any material way, particular over millions of prescriptions. The drug must act predictable, whether name brand or generic.
The FDA lists these in its monograph, that the chains of oligosaccharides require a sophisticated method for adequate characterization, because they are created by chemical reactions. Different chemical reactions can produce chains of various sizes, composition, and sequences. And unlike traditional small molecule drugs, that are relatively easily characterized, with lovenox, these different chemical reactions can alter material characteristics of the drug such as absorption, distribution, metabolism, excretion, and efficacy of this drug in the body. Any directly substitutable generic lovenox has to respond as Lovenox, and cannot have its own unique quirks in this indication.
This is why the FDA has approved four distinct and separate LMWH drugs, because those different chains produce different characteristics, and they are not interchangeable with each, despite all being LMWH.
The FDA thus goes on to conclude that a manufacturer MUST be able to reproduce these distinct features of the drug. Just demonstrating Xa:IIa activity assays is not enough. It requires "state-of-the-art" analytical methods to SHOW THAT the STRUCTURAL FEATURES of oligosaccharides in the generic enoxaparin sodium are equivalent to Lovenox.
Therefore the usual compendial requirements are inadequate and a rigorous, 5 step, overlapping criteria was created.
Because MNTA fully characterized the drug, they could meet this standard. Because Teva has not, to date they have not been able to meet this standard. All the paperwork we have available indicates that Teva has admitted they have not characterized the drug, but they have done well enough.
The big fear, uncertainty, doubt, is that generic drugs are usually approved under what is undoubtedly the standard that Teva can presently meet, and Teva has probably gone much farther than that. The conventional wisdom is therefore it is just a matter of time.
This ignores that the FDA has thrown out the conventional wisdom with Lovenox. They are requiring that all of what is usually considered "extraneous" strands, perhaps "contamination" be reproduced as well. Something Teva has never had to do before.
So we sit here, asking ourselves: (1) is this really true? The FDA is really setting the bar this high? We doubt this even as we are presented with another biological that was attempted to be genericized back in the 1990s, and all comers failed. The FDA set the exact same (or near same) bar for that drug, and (2) even if this is the case, is it not likely, that Teva will get around to doing just this anyways?
I don't know. I just know what I read and hear. From what I read, yes, the FDA has really set this very high bar and standard. Full characterization is possible, and even when it was not, the FDA still required in the past for Premarin. In the Premarin monograph, if the drug could not be sufficiently characterized to include all its structural components, that basically, trials needed to be run to determine what had pharmacological significance and what did not. At least that is the way I read it.
So what we have here is the same thing. MNTA has no need to run trials or prove anything pharmacologically, because they have characterized and reverse engineered the product to near identical specs. Teva, however, is in bind, because they have not.
But it is still Teva, it is still generic drugs, and it is hard to believe Teva may not succeed, like so many failed with Premarin.
It is hard for me to believe as well. Teva management certainly has not given up hope. And we do not know what Teva is doing that might get them over the goal line.
But it is what it is, and as long as this fear, uncertainty, and doubt exists, there is potential for a lot of upside. This all said, does anyone believe that Teva can pull it off? And if so, how and why can they do it, now that we know the current and historical FDA standard in regard.
I just don't see how the FDA can approve an identical generic with known characteristics (because it is proven to be the same) and give identical approval to an otherwise approvable generic (if this were a usual generic drug) that will have unknown properties and characteristics and call it the same as MNTA/NVS's generic, and have them all be interchangeable. How can Teva pull this off without clinical trials absent sufficient characterization to reproduce all these oligosaccharide chains that all "may" we do not know, but may have real and material meaning in regard to how the final drug will behave.
I know, just trying to make myself feel better, but intellectually it is quite sound. I just don't know (not being a drug developer or chemist) what Teva can do with a drug that was developed without full characterization to convince the FDA that its lack of full characterization is nto clinically meaningful.
Anyone have any ideas? If Teva originally produced the drug without full characterization, and Teva cannot reformulate the drug without essentially filing a new ANDA (which would be public knowledge) then I don't see how Teva can fix this. But I'd like some opinions as to how they might from those with thoughts on the matter.
Tinker
Teva can reformulate the drug, but this would be tantamount to starting from scratch with a brand new ANDA.
Safe to say then, that if Teva had reformulated it, that would be of public record and we would know of it.
Thanks Dew.
Tinker
Teva's letter specifies that the rings in their generic were "similar" to that of Aventis/Sanofi, and that additional studies thereon were on-going and would be submitted.
Teva does admit that they have not fully characterized the molecule (by clear inference) and they discount the newly discovered chains as falling under the legal classification of "no clinical significance". Whereas Aventis "speculates" these newly characterized chains do have clinical significance, such as a half-life difference on their anti-Xa activity.
Teva basically stating that all these newly discovered chains "potential clinical significance is doubtful".
I would imagine that MNTA discovered quite a few more than Aventis/Sanofi brought up in their citizen petition.
In any event, my point made. I think Teva has to convince the FDA that the disparities in Teva's formulation, disparities that were probably primarily revealed from MNTA's applicatio and characterization of the drug, are without clinical significance.
The FDA monograph however seemed pretty clear that the FDA had some real concerns about these chains. The historical article on Premarin is consistent with this view point as that is how the FDA treated the generic appliations for Premarin. If there were new chains discovered, and we suspect they may alter the characteristics of the drug, then the applicant has to prove to us otherwise that they are clinically insignificant before we will approve their drug.
When I talk this much we are usually in trouble. Logically, in context with everything I've seen, this is a proper analysis. The real key lies in what is going on in the real world with Teva and the FDA. I still don't think Teva has a sufficient drug, unless they can prove to the FDA that all these new strands that MNTA characterized in Lovenox, and which were mentioned in the FDA monograph, can be shown to be clinically insignificant or otherwise replicated in Teva's drug.
Tinker
http://www.fda.gov/ohrms/DOCKETS/dailys/04/sep04/091504/03P-0064-emc00001-01.pdf
Here it is. 7 pages, so it was short and sweet.
Let me know what you think it means in regard to Teva's current application.
Tinker
TripleCutter,
Great article. I think that has to be bullish for MNTA in that the FDA did not bend and lower the standards in the monograph but rather stuck with the science, required the applicant company to prove itself, including on ambiguities (here it looks like Teva will have to answer why chain x or y is not in their drug and why should we ignore that fact), and if anything, ratcheted the standard upward as more science came forward as to the complexity of the molecule in question. Basically the FDA was requiring nearly full characterization of the Premarin molecule as it learned more and more about this chain or that chain that appear to change the characteristics of the molecule, and would not allow just a showing of the core aspects of the drug to allow the generic.
I wish I knew the process better as to what Teva was doing to its aNDA. Can Teva modify the drug it submitted to the FDA and reformulate and recreate it as they go forward? Or is Teva limited to its initial offering and cannot change the underlying drug they put forward? From Sanofi's lawsuit, and from my understanding, Teva is stuck with the drug it produced in 2002 and submitted the ANDA for, warts and all.
Again, and I may be very wrong, but if Teva is stuck with the initial drug that it put forward 7.5 years ago in its ANDA, as it was submitted back then, then all Teva can argue is that the parts not replicated in their drug don't matter, and get the FDA to agree to that. If the FDA cannot be convinced of this, then TEVA's drug cannot be approved under the monograph the FDA provided IMO. Take it for what it is, I'm not a scientist, just a detailed reader, but I don't see what else Teva can argue if their molecule does not characterize and replicate all these various chains that MNTA has identified and replicated, because these chains are ambiguous and are likely to change the characteristics of the molecule to a material degree, even if no one knows exactly how or by how much.
In regard to the bolded section, although speculation, but I bet that MNTA's characterization of the molecule brought to the attention of the FDA many before unknown chains in the molecule, and actually makes it easier for the FDA to do its job and harder for an applicant, who now has to explain to the FDA why the newly found chains in the molecule don't matter and variance from them, or absent of them don't matter. Speculation, but I think it probable that this is the case.
Tinker
<<<I think (it's my opinion) that TEVA is very likely based on what I have read.>>.
Given what is out there to read, it must be the two statements from Teva management. The same statements that were ridiculed by MNTA management for over a year.
<<<The stock price is just a popularily contest and people vote with their $$$, today the people have declared that TEVA is more likely then not compared with a day ago>>.
But that is the whole advantage that investors have, they look beyond the next 24 hours and can see past the current frenzied opinion. DNDN is probably the best such example of the last few years, ELN was another one. That is how I made my money on MNTA when it fell in the single digits based upon its losing popularity because it was perceived that the FDA would never approve the application. That is how you get triples in relatively short order.
Which is why I asked you the question. Real money is made by looking past the mood of the moment and to the real issues at hand.
Unfortunately, unlike with many other situations in the past where you just knew what was going to happen, I don't know if the FDA will ease up on Teva and give their application an approval. They haven't going on 7 years, and they haven't considered Teva's application in a timely basis with MNTA. In fact, what we know from Teva is that they still are not ready to approve it. The application is not just sitting there, it has simply been failed to be approved and Teva is still working on issues with it.
The reason for why I suspect Teva has not been approved after all this time, and as not approved with MNTA was posted in one of my prior posts today in great detail. Basically, neither Teva nor Ampha could produce sufficient information or methodology to even give the FDA a framework to create an approval framework for a molecule like Lovenox. MNTA, however, did just that, and was approved based upon the framework that MNTA technology made possible.
Now the question is, will the FDA lower the bar for Teva, and can Teva fit itself into that framework? I'm sure they are trying mighty hard. I'm sure the FDA will listen and give them a chance. But I don't see how Teva does it without the FDA bending and lowering the bar. Teva's Lovenox is not the same as MNTA's lovenox. I could not in good conscience have a family member of mine interchangeably use Teva's Lovenox without clinical trials as if it were brand name Lovenox or MNTA Lovenox. Can the FDA get beyond this?
I wish I could answer that question for you with more certainty. But, at the current price, even if the FDA decides to lower the bar for Teva because they've done an otherwise acceptable, if not up to MNTA par job, then the share price is not far from bottom. On the other hand, if the FDA sticks to the rigors it set, which from all the documentation we have is a higher standard than Teva can possibly meet using the methodologies and technologies they have employed, the upside from here is 3, 4, 5x, not including M356 or M118.
That makes for a good risk reward if you look past the next trading day. More speculative than I usually like. I like certainty. Like I knew MNTA would be approved, which is why I originally invested. Now I stay invested only because the current price represents a good portion of the downside, and M356 provides a large amount of upside.
I appreciate your perspective from your investing technique, which is more short term trading. I've just rarely made money trading on a day to day basis. I've done very well on a few special moments a year, but that is just not my forte.
Which is why I am more interested in reality as to where the stock price is in comparison to the downside, the potential upside, and the reality as to whether or not the present fear, uncertainty and doubt is real, feigned, or just overblown.
According to you, it is perception from information provided by an analyst who was quoting the Teva CEO and the Teva CFO from publically available (and in fact heard by many on this board statements) statements, and all this in the midst of insiders automatically selling to pay off their taxes.
Does the market know something? No. Not anymore then when MNTA "surprisingly" got approval from out of nowhere and the shares skyrocketed to $26. Is the market anymore accurate now? Probably not. I've seen leaks happen from the FDA, but all in all, the FDA is very good (compared to most) in not leaking information. That is how DNDN goes from $2.50 to $40 in short order, as an example. How MNTA went from a TECHNICAL downtrend and nearly doubled overnight and then lost 30% just as quick.
Tinker
Wallstarb,
Just trying to get how you calculate that Teva and Amph are right behind when their applications are two years older than MNTA's, and their drugs, from all the evidence, have not characterized the drug, nor replicated the drug, to near the degree that MNTA has.
I am not saying that the FDA might not approve their applications despite this. Good enough might be good enough.
But I've laid out my rationale. Do you have rationale for your conclusion, or is it just a conclusion. If so, I'd like to hear it.
Thanks.
Tinker
<<<Teva in its citizen petition wants the FDA to define sameness as the same degree of inhibition of Factor Xa and Factor IIa as in branded Lovenox.
On the other hand, SNY argues—and MNTA agrees—that the FDA should define sameness as the same degree of all of the constituents in branded Lovenox , not just FXa and FIIa.
Sure if you get Xa and IIa right it should work on those targets. But there is no way without studies to know what other effects that are different may have been introduced. MNTA is right about sameness. It either is the same and should be substitutable or it is not and you need studies
MNTA's position of requiring sameness suggests MNTA has the ability to exactly replicate Lovenox, while Teva's position reveals possible weakness.>>>
Up until this morning this was the general feeling about a possible Teva approval. This is a summary from others, consistent with the Citizen Response Letter to Aventis, Teva's response thereto, and the monograph provided by the FDA, as well as Craig Wheeler's comment about requiring 100%, not 80% characterization to obtain approval under the standards the FDA created.
One analyst note, contrary to the opinion of multiple other analysts, contrary to our opinion, with the note taken directly from public statements that many of us heard last week from Teva's CEO and CFO, who have no more idea than Wheeler did as to when, or if, ever, the FDA will approve their drug, and suddenly everyone appears to assume that a Teva approval is imminent and inevitable.
Well, it may be. But nothing has changed other than boy can that brokerage work over the independent investor with anxiety, worry, doubt, fear, and uncertainty.
What I write here won't change whether or not approval is ever granted, but has anything actually really changed? Does anyone here have a changed opinion as to Teva's chances of approval given all that we know?
As I've stated earlier today, I don't think Teva can be approved without some flexibility on the part of the FDA. Teva simply has not characterized the drug. They have recreated core aspects of the drug, but they have not characterized the drug down to the detail necessary to meet the requirements the FDA laid down.
Now perhaps, since Teva is a fine company, they have put something together that may otherwise impress the FDA. As the FDA did not say that full characterization was necessary.
But given Teva's argument, of to define sameness as the same degree of inhibition of Factor Xa and Factor IIa as in branded Lovenox. DOES ANYONE HERE THINK THAT IF THIS IS WHAT TEVA HAS THAT THE FDA WILL BEND AND BE FLEXIBLE ENOUGH TO APPROVE IT?
I'm not an expert, I don't work for the FDA or anything close, but can Teva somehow meet the exacting standards the FDA set down if what they have is what they say they have?
Just curious if anyone's opinions on this have changed due to the statements of Teva's top 2 managers and the reiteration of those statements by a brokerage.
Thanks.
Tinker
<<<The trouble is whatever you may or may not believe about Teva's chances, it's going to be an overhang on the stock. A few quarters to themselves would go a long way.>>>
No doubt about it, but I can look past a few quarters, because at some point that overhang dissipates and the stock rises as it does and the cash flow starts coming in.
I am just really curious as to how Teva (if it does get approval) is able to garner it, as it does not look to me, if the FDA sticks with its criteria, that there is any reasonable way for Teva to manage to gain approval absent some more "flexibility" by the FDA in evaluating Teva's application. Such flexibility cannot be ruled out. Anyway, that is my conclusion, and probably the basis of Teva's on-going strategy to gain approval despite not having replicated the drug to the degree and extent that MNTA has.
Tinker
<<<Teva President and CEO Shlomo Yanai said last week, after presenting second-quarter results, that he had good reason to believe his company was close to getting approval for its generic version of Lovenox.
The company's chief R&D officer, Benzion Weiner, also told Israel's Calcalist financial newspaper this week: "We are waiting to receive the approval soon and the chances of receiving it is high."
A Teva spokeswoman declined any further comment on timing.>>>
This is the sole source of Anderson's information. I read both quotes last week, verbatim. Others on this board did as well.
Teva may be able to work with the FDA over the coming months and get approval. Clearly, Teva has not given up on its application yet, and its application is not secretly rejected and just not disclosed.
But this analyst report contributes absolutely ZERO new information. It says "may" be approved in the coming months to end of the year. BUT WE ALL, ALREADY KNEW THAT.
In the analyst I posted last night, it did not seem likely that Teva could obtain approval if the FDA stuck to the rigor it specifed on the MNTA approval, but the FDA, after cajoling and working with Teva may institutionally become somewhat more "flexible" in interpreting its criteria. Something I stated last week. And if so Teva "may" to use the term in the Bernstein report get approval in the coming months.
But Teva also "may" not get approval. And if Teva gets approval it "may" not be directly substitutable as MNTA's approval was.
Who knows. But as I have seen over the years in biotech, it is not so much that we already knew the information, but rather what moves the share price is who eventually regurgitates it and spits it out through the proper channels.
This report is bunk, it was not even linked to Teva in Yahoo!, and is clearly a MNTA stock focused report (and not Teva in intent), but that does not change the reality that it might come to pass. Just that, this report has no more information then we already had.
We shall see.
Tinker
RockRat, in regard to lovenox, I've gone through the Aventis Citizen Petition you linked to, pulled up the Teva response thereto, and went through the FDA monograph. I do not read it as a chemical expert but in regard to comparison of the relevant parties to ascertain what is really going on.
I have to say that I agree with you on the rigidity of the requirements that the FDA put forward. This is summed up in the monograph that emphasizes a "sophisticated set of analytical methods for analytical characterization."
In particular, I find persuasive part of the Aventis Citizen Petition that the FDA actually rejected, that the manufacturing process for Lovenox has to be identical.
Clearly the manufacturing process does not have to comport with that used by Aventis, however, to obtain the sort of detailed equivalence that the FDA is looking for (and they cite the 4 brand names of LMWH products that have been approved with distinct names because the small differences from each of their respective manufacturing processes creates real and substantive differences in characteristics) you either have to have the same manufacturing process, or you have to have detailed characterization of the molecule sufficient to reverse engineer the drug to sufficient exacting standards. And these standards are exacting (again referring back to the 4 distinct brand names of LMWH, as small differences create real and material substantive behavior of the drug).
It is clear that Teva, in its application (most of the work was done on this application by Teva back in the late 1990s, early 2000s, pre-dating MNTA's more sophisticated methodologies) stuck primarily to the industry standard for replicating generic drugs, and is arguing that the degree of sameness need not be exacting, and can be similar enough. That full characterization is neither possible nor necessary, and that sufficient "sameness" (quoting from small molecule definition of the word) is what is required and sufficient.
The FDA made clear in its response to Aventis that 100% characterization was not necessary, and exact chemical replication was not necessary. Teva prevailed on this issue. However, in the FDA's approval of m-enoxaparin and the criteria that it created to set the standard, it basically handed Aventis a victory by setting the barriers so high in that MNTA did not need to fully characterize the molecule (as Aventis argued), but it nevertheless is hard to imagine how you could sufficiently recreate and characterize the molecule with the required rigidity without either (1) utilizing the exact manufacturing process, or (2) fully characterizing the molecule, at least to a very great degree. I.e, although the FDA largely rejected Aventis's Citizen Petition, the FDA's final standards on generic lovenox are such that Aventis practically won on not all, BUT much of what it was arguing for.
Understanding and recreating the known "active" ingredients itself, demonstrating similarity, and in vivo pharmacodynamic profile is not going to cut it. And that is what Teva has done.
Not bad for a lay person. Is that your understanding of the issue Rockrat? Dew?
Given this analysis (if accurate) it does not seem possible that Teva could meet the criteria, as its processes are not exacting enough. The FDA made clear that exact characterization is not necessary, BUT so much of the complex details are required to be recreated correctly that one could not manage to do it by chance as they go about recreating the core aspects of the drug as Teva has done.
Thanks for any input.
Tinker
Thomas,
Given that you are probably sitting on a triple (I got a nice triple in about 9 months or so) it is rational to consider, okay, take profits or risk a TEVA approval (we discount the lawsuit as nothing, although it is not quite nothing, but I'll assume that it is nothing for now).
All this said, M356 is what convinced me to keep it here. M356 alone appears to be worth more than M-Lovenox (when/if it is finally approved - even if approved before patents expire if their is a loss in the patent suit as the market will start discounting its large value as the clock ticks down), and it means we are not sitting on a one time, take your money and run asset. There is real and legitimate follow-up here. I can therefore, as long as I have patience, not shoot myself if it does crash back down to $15 because TEVA does somehow garner approval. Now if it crashes to $5 if the lawsuit pans out for Sanofi, well, that is a risk I'm discounting to practically zero at present.
Given that I don't diversify very well, one has to keep these things in mind. So trying to value the downside is as important as valuing the upside. Which is why I've been feverishly trying to do so over the last few days. Risk/reward is the nature of any investment, and I only invest in very few.
It is why I bought in the single digits, and not at $20 or $15 a share, with biotechs, there is so much volatility, you have to ascertain the risk/reward and in the single digits it was undeniable, and if the downside is 20%, then still undeniable. Although, like another poster suggested, it will fall (at least temporarily) to less than $18 if Teva were to garner approval I would guesstimate, probably to $15, so a 31% downside, but with M356 still ahead of it as another upside. Without M356 as a back-up then it is rational to reevaluated the risk/reward at this level and adjust.
August 17 will be another important day.
Tinker
<<<Canaccord screwed up by writing that. M356 (generic Copaxone) is a 50/50 profit split between NVS and MNTA regardless of the number of generics in the market.>>>
That is what I thought. Have to start trusting myself over these brokerages that keep doing stupid things. So even in the multiple generic scenario for Copaxone (which is less likely to exist than with Lovenox) the M356 valuation has to exceed Lovenox (asuming approval). If a generic Lovenox (with multiple generics) is worth $13 using their assumptions, then an approved M356 is worth quite a bit more, even in the multiple generic scenario.
My rules for biotech investing start with know the drug works, know the drug works very well, and what is their back up. MNTA is meeting these criteria in spades.
Thanks Dew.
Tinker