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This from my severest critic who I love and respect: "Dick
I am no fan of socialism but this post (my previous one see reprint in 1 below) has really gone overboard and your blind hatred of socialism causes you to loose any objectivity. Sweden is pretty socialistic; however, our Swedish exchange student who it seems not only has two tooth brushes but two homes; one in the country and one in Stockholm. She and her family seem to be living pretty nice although they pay for it in taxes. Also, I take offense at your stab at the VA, having been a VA provider. Sure there are many problems with the system, but there are many problems with our private system. I'll give you the names of a lot of veterans who are very happy with the VA, just you ask around. Lighten up, you will get constipated. Try, although I know it's difficult, to be a little more objective. I am sure some of your readers will appreciate it and not be laughing up their sleeves at you. Just some friendly advice. Best wishes
B----
My response: "Thanks, you are my most severe critic.
First, Sweden is a small homogeneous country until they decided to let in tens of thousands of Muslims and now they are thinking of exporting them.
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Second, Sweden is rife with anti-Semitism as a result of allowing in these Muslims,. My sister in law is Swedish and she became an American citizen, taught Lynn's brother and married him. She came here for dental and medical needs. Her family still lives in Sweden. I have never been but to hear her tell it Sweden is a lovely small country and nothing like America.
My house guest this weekend is the former retired Lt. Col. and head of orthopedics at Walter Reed. He knows something about Veteran care and I might generalize but it does seem the Veteran's Health care system is more broke than fixed but you no longer hear about it. I would not want it to become a standard by which the rest of America's health care was judged but that will happen when Bernie has his way. I doubt you would either.
Bernie's attack on the pharmaceutical industry last night was based on generalizations and a few corrupt actions by equally greedy executives but we produce more drugs in this world and the rest of the world benefits. If we depended upon the drug products of the rest of the world we would not have the life expectancy we have. Furthermore, for every drug success the costly failures have to be paid for so research continues. Every pill that is sold and passes the FDA bears some of this cost. The public is too dumb to understand this fact. (See 1a below.)
Again my sister in law just retired from The FDA having worked there for over 30 years. Her husband, Lynn's brother, retired ten years ago as a researcher with NIH. Yes, I am biased because I have heard their horror stories and even after discounting them they tell about another inefficient government bureaucracy where the best leave after a while or stay and hole themselves away from the impact of incompetent management as did my brother in law who did cancer research.
If you think socialism is the answer to America's problem I commend you read The Road to Serfdom by Hayek. Every nation, where it has been tried, loses out to capitalism which ain't perfect either, just better than all the other system designed by man. Freedom does not equate with Socialism.
My bowels work fine, just had a colonoscopy but I still believe Hilariousand Bernie are full of shit and their adorers are willing to buy into their divide and conquer rhetoric and we see what Obama has done for us with his Hope and Change and they will simply drive more nails into our once great nation's coffin.
You have your views, I have mine. I find little of comfort in eating what Hillarious and Bernie are serving.
Stay well. We need to have lunch again, just you and me. I will call. Me"
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I am no pollster or mathematician but if the lower tier Repub candidates begin to realize they do not have a chance and withdraw, I daresay most of their votes would not go to Trump. If they persist against rational odds they will force a brokered convention and eventually wind up allowing Bernie, the wild eyed aged socialist, to be elected or Hillarious, who might be indicted and forced to pardon herself from the Oval Office.
Takes a lot of ego and professed love of America to square with that thesis. (See 1b below.)
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This Jordanian-Palestinian politician and author believes Saudi Arabia's Crown Prince Mohammad Bin Salman, is bringing Iran to its knees. You decide. (See 2 below.)
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Water boarding tunnels in Gaza? Are Israel and Netanyahu restrained by Obama? (See 3 below.)
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Dick
1) Reprint from previous memo: "... I would love to peer into the medicine cabinets and pantries of those who are enamored with Bernie. Why? Because I doubt they have one tooth brush or one of everything. One of everything is what Socialism produces. The state dictates. There is no competition and without competition there is no diversity. It eventually becomes a one size fits all world and for those who are used to a vast array of products and choices dull would happen quickly but then 'what difference does it make" until, of course, you experience the consequences of Bernie's "political revolution."
When people are dispirited, as far too many Americans are, they often drop their guard and turn to the magician throwing the dust of "real change" otherwise, why would they have fallen for Obama and his hope hype? Now what we are witnessing is another demagogue taking advantage of an accumulation of disappointments and failed responses to the problems we face.
Go back and watch the videos of the crowds responding to Hitler's speeches and you will see the cheering crowds responding to Bernie's damning of Wall Street etc. God help this nation if he gets elected because he will outdo Obama in shredding what is left of our freedoms, independence and economy. That is the consequence of what Socialism does.
Despair and ignorance are the food on which fools thrive and demagogues score. After his victory speech tonight I suspect Bernie will have added another nail to the market's coffin. His attack on the health care industry is right out of a radical playbook playing off the frustrations of the mindless."
1a)
Generic EpiPen: What's The Hold-Up?
Summary
Teva has still not received FDA approval for its generic EpiPen.
The company is expected to announce the receipt of a Complete Response Letter during its conference call on February 11.
The potential roadblocks to gaining approval are discussed.
Thursday morning (February 11, 2016) will likely prove to be an inflection point for several stocks. That's when Teva Pharmaceuticals (NYSE:TEVA) will release its Q4 and FY 2015 results, but more importantly, will host a conference call with financial analysts as well. A major question from that call will be the status of its ANDA for a generic EpiPen, and in particular, whether an AB rating is still attainable. Not only could an AB rated Gx EpiPen bring in near $500 million a year in high margin sales for Teva, but it's likely to become a source of sustainable revenue as well, especially given how hard obtaining approval has proven to be.
In addition, the fate of Antares Pharma (NASDAQ:ATRS) hinges on the FDA decision, and Mylan (NASDAQ:MYL) will also be volatile depending on the outcome. Antares will supply the auto-injector (AI) for Teva's generic if the FDA ends up approving, and Mylan could face severe revenue and profit headwinds, as its flagship specialty product faces generic competition. Pfizer (NYSE:PFE), as the supplier of EpiPen AI (through its Meridian Medical subsidiary), would also see some impact, although it's more of a rounding error for a company of its size.
So without further ado, let's look at the current status and where the potential issues may lie.
(Source: Citizen Petition Supplement)
Background
Going back to the fourth quarter of 2014, Antares first announced that it helped Teva submit the final amendment to its ANDA for the generic EpiPen, and that further, an AB rating was expected (see this article for more detail). Under a settlement from patent litigation, Teva agreed to launch a Gx EpiPen no earlier than June 22, 2015.
Obviously, the FDA had not approved yet, and Teva later acknowledged that the FDA target action date was December 10, 2015. That date has also come and gone, and up to this point, the exact status has not been updated other than: (1) Antares indicated in a January 14, 2016 corporate presentation that it had "recently received questions from FDA as part of the ongoing active review of the application and is currently formulating a response", and (2) Teva IR indicated that it expected to receive a Complete Response Letter (CRL) from the FDA in late January. Whether it's completely unrelated or a simple coincidence, you may find it interesting that Antares replaced its CEO on January 24.
At this point, I expect Teva to announce on the conference call that it received a CRL, although the contents of the CRL will determine which way the inflection point is for each company involved.
Potential Delays
On the Q3 2015 conference call, Teva first announced that the company no longer expected approval in the second half of 2015, as previously communicated throughout the year. Management noted that the ANDA review process was just simply not far enough along, and that they also expected a CRL - possibly just to give the FDA more review time. This really wouldn't be all that surprising given the huge - and well-publicized - ANDA backlog that the FDA is trying to work through; however, Teva has been working on the ANDA for the better part of a decade. But given the more recent comments from Antares and Teva, I believe the CRL will have some actual meat to it. So, here's my due diligence into the factors that I think may be holding up approval:
- Sameness requirements
- Additional injector scrutiny
- Labeling/risk mitigation
Sameness Requirements
Although it can't be completely ruled out, the sameness requirements are the least of the three concerns I have. Antares' injector was similar enough to the EpiPen that the FDA accepted the ANDA and that Pfizer filed patent litigation. Additionally, the FDA was very clear in its 2010 denial of Dey Pharma's (now a subsidiary of Mylan) Citizen Petition (Docket No. FDA-2009-P-0578) that an AB rated generic need not be exactly the same. Specifically, the FDA indicated that (my emphasis added):
... an ANDA and RLD may have some auto-injector design differences as long as these differences "do not significantly alter product performance or operating principles and do not result in impermissible differences in labeling"
The FDA went on to state that it agrees that the emergency-use situation of an EpiPen does require particular vigilance in making sure a generic version can be used as safely and effectively as the RLD. This means the FDA may:
require further studies, require human factors studies, recommend alternative regulatory pathway, or decline to approve the application under section 505(j) of the Act.
However, this is where the water starts to get muddied. Although the FDA acknowledges that further studies may be necessary for approval as an ANDA, only certain data can be reviewed to determine AB generic suitability:
... for a combination product approved under section 505 of the Act, we will consider whether particular auto-injector design changes would require data beyond that which can be reviewed under section 505(j).
Essentially, this means if the FDA is going to require data typically associated with an NDA, then it would recommend the application be re-submitted as a 505(b)(2). This would likely mean the game is over for Teva and Antares, while Mylan retains exclusivity of its blockbuster drug.
Mylan essentially made this same argument in its January 2015 Citizen Petition, although the FDA ended up denying that petition without response. Of note, the company did submit a "Generic Epinephrine Auto-Injector Handling Study" dated April 21, 2015 as a supplement to its Citizen Petition. The Handling Study was Mylan's attempt to show that the Antares/Teva device could not be used as a true substitute to the EpiPen.
Without wasting too much time on it, I'll basically say that the whole study was flawed in concept. All the participants were screened so that only those trained to use the device were selected, and further, all participants were confident in their ability to properly use the device. In addition, 80% of the participants indicated that they practice with the device. This created inherent bias as to how the participants would react to any differences between the two injectors.
Not surprisingly, the conclusion was that the supposed generic (remember that only Antares, Teva, and the FDA have the actual proposed generic - Mylan just created a prototype based on Antares Otrexup device/instructions and a picture of the device from a 2012 investor presentation) results in a failure to deliver therapy due to "important differences in operating principles." However, if you dig into the conclusions at the end of the document, you'll notice the tone changes a little:
This is not to suggest that every patient or caregiver prescribed an EpiPen auto-injector, if dispensed the proposed generic epinephrine, would experience a meaningful delay or complete failure in delivering an injection. We are concluding, however, that the proposed generic device will produce a predictable number of injection failures (or delays in therapy) attributed directly to the product's specific design similarities and deviations relative to the EpiPen auto-injector.
Therefore, the real data that would help to determine sameness is the predictable number of injection failures/delays for a more representative - and unbiased - sample of users. Given that a large number (if not most) of EpiPens are tossed out upon expiration and not actually used, I doubt the majority of potential users are well trained and confident in their ability to use the device. And considering the number of people who have accidentally fired the device and/or stuck their fingers/thumb, I'd venture a guess that Antares/Teva could develop a study showing the same results for the EpiPen depending on the inclusion criteria.
Another really interesting aspect to the "sameness" requirement is that the FDA previously allowed Dey to market an updated AI while simultaneously working through old inventory (from the Dey CP denial):
Third, while the Petition suggests that any change in a generic version of EpiPen auto-injector raises the possibility for patient misuse and therefore significant safety or efficacy concerns, we note that Dey currently markets both the new and older versions of the EpiPen that actually have design differences from each other of the type that you assert are critical. FDA did not limit in any way Dey's ability to market both designs simultaneously while existing supplies are depleted. We note that EpiPen injector is marketed with a trainer product, and therefore, any generic EpiPen injector would be also required to have a trainer product.
Taking all of this information together, my opinion is that the sameness requirements are not a huge hurdle to overcome, especially given the importance the FDA has previously asserted about the trainer device being required for a generic as well.
Additional Injector Scrutiny
On October 29, 2015, Sanofi (NYSE:SNY) recalled all of its Auvi-Q injectors due to potentially inaccurate dosage delivery, which may include failure to deliver the drug. At the time, I must admit that I may have brushed this off too lightly as just Sanofi-specific. But now I wonder if this caused the FDA to take another look at its requirements to ensure this doesn't happen again.
Has the potential for inaccurate dosage delivery been an issue since FDA approval? Could the FDA have caught this during its review of Sanofi's NDA? Should additional testing be required for all injectors - especially for emergency situations - prior to approval? These are all questions the FDA may have started to investigate, and possibly a reason for the delay in reviewing Teva's ANDA. Ultimately, I would think this is an issue that can be resolved, but it may be additional information that the FDA is requesting from Antares/Teva in the potential CRL.
Labeling/Risk Mitigation
The labeling and/or risk mitigation is the most likely element in the potential CRL. How will the product be labeled so that it can be considered a substitutable generic by meeting the "permissible differences in labeling?" And will the FDA require a Risk Evaluation & Mitigation Strategy (REMS)? A major part of the FDA review may be to determine if a cheaper generic outweighs the risks of the potential misuse of an emergency and potentially life-saving drug:
(The following images were sourced from an FDA webinar)
According to the FDA, the three main elements of a REMS for generic drugs are: medication guide, elements to assure safe use, and implementation system.
1b) The Left-Right Revolt
Sanders and Trump ride very different populist uprisings in New Hampshire.
Americans keep telling pollsters they’re unhappy—or worse—with their political leaders, and on Tuesday they proved it in New Hampshire by handing victories to a 74-year-old socialist and a blustery businessman with no political experience. Bernie Sanders and Donald Trump are still a long way from the White House, but their victories reveal parallel but very different popular revolts on the left and right.
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The uprising on the left is perhaps most surprising given that Democrats hold the White House, and Hillary Clinton campaigned to build on President Obama’s record. But in New Hampshire the revolt was ideological and personal against Mrs. Clinton and the status quo.
Mr. Obama tilted before the Iowa caucuses toward Mrs. Clinton as his preferred successor, but New Hampshire shows that his Presidency has been a hot-house garden for nurturing progressives. According to the exit polls, nearly seven in 10 Democrats described themselves as liberal, up from 56% in 2008. Roughly a quarter described themselves as “very liberal,” and Mr. Sanders won them two to one.
Mr. Obama calls inequality the defining issue of our times, and Democrats believe him. A third of Democrats said it is the most important issue facing the country, and about 70% of those voted for Mr. Sanders.
Mrs. Clinton won the New Hampshire primary in 2008, but this year Democrats seem to have rejected her on personal and character grounds. Mr. Sanders won nine of 10 voters in the exit polls who said that only Mr. Sanders or neither of the two candidates were “honest and trustworthy.” The Clinton campaign has tried, as it always does, to plow through her email scandals by portraying them merely as Republican attacks. But even many Democrats don’t believe her anymore.
Mrs. Clinton now finds herself in a populist showdown she never anticipated and doesn’t play to her strengths. She’s best as a machine candidate of the unions, feminist volunteers and wealthy environmentalists. Mr. Sanders is motivating the younger liberals who were also drawn to Mr. Obama and who are voting for the Vermonter by three or more to one.
The Clinton campaign will console itself that the campaign now moves to states where the electorate will have more minorities and fewer gentry liberals. And to win the nomination Mr. Sanders will have to show that he can expand his support among minorities, especially the black voters who are so important in southern primaries.
The Vermont Senator’s other great obstacle is that many Democrats still fear that a self-avowed socialist can’t win in November. But that argument becomes less damaging as it becomes clearer that Mrs. Clinton has weaknesses that also could be fatal in the fall. As Republicans get closer to nominating the mercurial Mr. Trump, more Democrats may also conclude that even Mr. Sanders could win so why not take a chance on their true heart?
Which brings us to Mr. Trump and the revolt on the right. This is less about ideology and policies than the businessman’s political style and Republican disgust with Washington. The New Yorker dominated the field with some 34% of the vote as we went to press, while no other candidate broke into the high teens. The victory showed that, contrary to Iowa, Mr. Trump could translate polling leads into actual votes. And it showed that the ceiling in his support is higher than many Republicans have believed.
The businessman did especially well among voters without a college degree, but his support was strong across most demographic and ideological groups. He’s the choice of voters who like that he “tells it like it is” and think he can change Washington. But the exit polls also showed some signs of potential weakness. A little less than a third of his voters said they liked Mr. Trump but had reservations. And his share of voters who said he could best handle an international crisis was below his overall vote share.
As for the others, Mr. Trump will be happy that no clear alternative emerged. John Kasich’s investment in the Granite State—100 town halls—paid off with a second-place finish. The Ohio Governor did well among independents and especially moderates. His challenge going forward will be that there are fewer of both of those voting blocs as the primaries head to South Carolina next week and elsewhere in the South on March 1. He will have to raise money fast to be competitive, as well as show he can win over more conservative voters.
Jeb Bush spent heavily in the state and has to be disappointed to finish in the mix for third or fourth place as we went to press. He has been performing better in debates and has the money to fight on in South Carolina, but he will have to show he can beat Mr. Kasich and Marco Rubio to go much beyond that.
Mr. Rubio may be the most disappointed by Tuesday’s result because the Florida Senator couldn’t build on his Iowa surge and suffered from his debate brain-freeze on Saturday. More late deciders turned to other candidates, and some two-thirds said that debates influenced their votes.
Ted Cruz also failed to capitalize on his Iowa victory, notably in failing to make inroads among voters who aren’t evangelicals or very conservative. The Texas Senator will find more fertile territory in the South, but his showing in New England bodes ill for winning swing states if he is the GOP nominee in November.
***
All of which means that New Hampshire hasn’t performed its traditional role of winnowing the field as much as usual. Chris Christie will find it hard to continue after his sixth-place finish, as will also-rans Ben Carson and Carly Fiorina. The rest have a case to fight on. But one big lesson of New Hampshire is that if the non-winners want to become the GOP nominee, they will sooner rather than later have to stop attacking each other and start educating voters about Donald J. Trump.
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| On January 11, 2016, Iran’s official media confirmed the state had filled the Arak nuclear reactor core with concrete. In short: Iran has killed its flagship nuclear site and its nuclear program is now limited to smaller projects, paperwork, research and, of course, propaganda videos. But how could this have happened? While the US-Iran nuclear deal does dictate that Iran must reduce the operational capacity of the Arak nuclear reactor in particular, nobody could have believed Iran would have jumped to execute this part of the deal so quickly. Iran has been known to never give up anything except for handsome rewards. Iran’s “sweet surrender” would never have been possible without the sophisticated and determined pressure of one country; Saudi Arabia, and one man; Saudi Crown Prince Mohammad Bin Salman. For years Saudi Arabia has been warning the West against the growing Iranian influence in the Middle East. What helps Saudi Arabia here is that it understands the region much better than many Western governments. When the revolution broke out in Syria in 2011, the West in particular dealt with it as local unrest, an armed revolution or a civil war at worst. Saudi Arabia understood clearly even then that Iran was on a mission to control Syria and turn it into terrorism export hub. While the world was busy trying to negotiate Syria’s future with both Syrian President Bashar Assad and Iran, Saudi Arabia was not wasting any time; it put up all the proper support for Syria’s only secular opposition body, the Syrian Opposition Coalition (SOC). Today, there seem to be no other moderate parties in Syria than the SOC, and on top of that the world is referring to Saudi Arabia for coordination with it on Syria as the only option left. Saudi Arabia’s effort to limit Iran’s power did not end with Syria. In an effort to fight back, Iran tried to destabilize Saudi Arabia’s southern borders by empowering the pro-Iranian Shi’ite militias in Yemen, the Houthis. These militias had become too strong, to the point of taking over most of Yemen, and eventually controlled the capital, expelling Yemen’s elected president. However, the Saudis weren’t having any of it – the Saudi crown prince and defense minister, Bin Salman, launched a fierce military operation to crack down on Houthis in Yemen. In Yemen, Bin Salman was focusing on massive surgical air-strikes by Saudi’s Royal Air Force – second strongest in the region – and avoiding sending in ground troops in order not to engage the Saudi army with the fluid and fast-moving Houthis militias. Since then Saudi fighter pilots have been clocking more flight hours than any others in the world. As a result Houthis have been scattered all over Yemen – an insult to Iran which had pledged earlier to support the Houthis to the end. Iran’s media even announced Iranian special forces and weapons were going to be flown to Yemen to support the Houthis – none of which happened as a determined Bin Salman ordered his fighter jets to impose an embargo on Iranian vessels and jets trying to enter Yemen. Still, Iran’s humiliation in Yemen was merely an introduction to what Saudi Arabia did next. It is no secret that Saudi Arabia is one of the world’s largest oil producers and therefore has a major say on global oil prices. Saudi Arabia has increased oil production to the point of driving oil prices so low that Iran has begun suffering. The Saudis can easily stand the decrease in revenues; Saudi Arabia enjoys a catalogue of natural resources and minerals besides oil, and on top of that has a rather Westernized economic model capable of surviving such a painful drop in revenues. For example, since the drop of oil prices Saudi Arabia began implementing social welfare programs for its citizens to create a safety net that secures them amid the economic downturn. Iran could not afford any of this, nor does it have a liberalized economy that could withstand such shock. In addition, Iran has been financing two major civil wars in Syria and Iraq, and supporting Hezbollah in Lebanon. Recent Arab media reports confirmed Hezbollah militants have been complaining of their pay being slashed in half, and Assad’s militias complaining about smaller government handouts. In other words, Saudi Arabia has pushed Iran to the edge and moved it from the offensive to the defensive, forcing it to accept two public humiliations, one in Yemen and the other at home when Iran literally buried its crown jewel in cement. Further, Saudi Arabia’s intelligence services began a relentless crackdown on Iran’s intelligence operatives in Saudi Arabia itself. There have been several reports of arrests and uncovering of cells. Crown prince Bin Salman didn’t stop there: Saudi Arabia carried out long-standing execution sentences of convicted pro-Iranian terrorists as well as others including Islamic State affiliates. One of these was Sheikh Nimr Al-Nimr, dubbed the “Shi’ite bin-Laden”. Nimr was a pro-Iran Saudi Shi’ite cleric who had been convicted of planning, financing, inciting and aiding terrorist operations on Saudi soil, in which several Saudis officers and civilians have been killed. Before the execution Iran’s media constantly warned Saudi Arabia it could “shake the ground under its feet” if Nimr were executed. Nonetheless, Saudi carried out the execution, and nothing happened, nor was Iran able to shake anything in the kingdom, adding another humiliation to the list. A non-Saudi Arab diplomat told me: “For Iran, Saudi Arabia’s execution of a Shi’ite terrorist godfather like al-Nimr is pretty much like the crucifixion of Jesus to his followers.” Saudi Arabia has been pressuring the Iranian bully politically, militarily and financially, as well as publicly humiliating it. Saudi Arabia may never have a peace treaty with Israel, but it is wise enough to take on Iran and limit its ambitions for regional dominance. Saudi Arabia follows Sharia law internally, but the outcomes of its foreign policy have been helping moderation and sanity in our troubled region. Those bashing Saudi Arabia must understand: undermining Saudi Arabia is direct empowerment of Iran. The author is a Jordanian-Palestinian politician. ============================================================================================= |
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