|
Post by matt on Oct 3, 2017 9:29:47 GMT -5
It is really hard to put a number on Danbury because most of the money spent was to create space to produce Afrezza. In a distress sale scenario, which is how most real estate lenders will look at structuring a sale-leaseback arrangement, the plant is only worth what the land and the shell of the building is worth minus the cost to remove any Mannkind specific improvements(that is required to make the building interesting for a new tenant or owner). The best comparable is not the historical cost Mannkind put into it or what it would cost to replace, but what other buildings of similar size and age are selling for in Danbury. The figures after the 2015 end-of-year write down is probably the most reasonable estimate.
It is just like a mortgage lender; nobody cares how much you paid for the house or the fact that you just invested $100K to improve the family room and the kitchen. If you have a four bedroom house on a street full of four bedroom houses that are selling for around $500K, then the bank will write a mortgage based on a value of $500K.
|
|
|
Post by matt on Sept 30, 2017 7:58:38 GMT -5
I have presented Afrezza to many GPs and all of them recognize the PK/PD as a big fing deal! And all of them recognize the lack of insurance coverage as being a big fing deal! I think that sums it up pretty well, and some are concerned about the "black box" warning as well. Any time there is a label revision, it gives the sales force something new to talk about with prescribing physicians who rapidly tire of the same old pitch from the same sales person. A change can only help open some office doors that are presently closed. However, I think changing the way the PK/PD is described in the label text is not going to change reimbursement. The PK/PD data has been out there since day one, and the adjectives used to describe it do not compel any insurance carrier to offer coverage or to move an already covered product to a higher tier. At the end of the day the top line of the label will still read "Afrezza (insulin human) Inhalation Powder" because fundamentally that what the product is. Afrezza is the only inhaled insulin, so it is already in a class by itself, but that has not resulted in coverage from most insurers. The fact that it is inhaled is precisely what gives the drug its faster PK/PD profile and this is no secret. The argument that insurance is required to cover all drug classes is not a good one, and isn't even true. When angiotensin receptor blockers were launched, most formularies did not cover them because there was an abundance of cheaper ACE inhibitors available even though ARBs have a better side effect profile. Now that amlodipine is generic, everybody covers ARB drugs but direct renin inhibitors remain uncovered for the most part. Three classes of drugs, three ways to treat hypertension due to overexpression of renin/angiotensin, but widely different coverage decisions. Insurance companies need to offer a treatment option for covered diseases and it would be different if Afrezza were the only insulin available, but all provide coverage for insulin in several forms and there is no additional entitlement to receive the best insulin.
|
|
|
Post by matt on Sept 27, 2017 17:05:18 GMT -5
Looking at the "printed labeling" documents it appears they don't yet reflect availability of the 12u cartridge, so it seems getting new data on this site in a timely manner is not guaranteed. As for MNKD's actions, might depend upon whether it's good, bad or between news and whether that news would be considered to be "material". If they get their "ultra" designation I would suspect they'll rush out a PR. There are two discussions to be had with FDA. The first is allowance of claims, and the second is approval of the label copy. The first is the tough part; the label text and printed materials can follow within a few days once there is agreement on what the company can say. It might be a few weeks before you see revised package inserts.
|
|
|
Post by matt on Sept 23, 2017 13:51:03 GMT -5
IF Afrezza obtains a new classification (ultra rapid, etc.), does anyone on this board know for a FACT, that PBM's have to cover the drug on their formularies? Must they cover the new drug class or can they choose not to? IF they must cover Afrezza in a new class, would it be a Tier 1,2, 3, or 4? We can all speculate, but does anyone here have experience working for/with PBM's? There are plenty of drugs, and drug categories, that are uncovered and that includes drugs in categories that are specifically excluded from Medicare Part D by law. Like any private insurance, if somebody is unhappy with the formulary they can ask for a waiver. To my knowledge, FDA never uses the word "class" in a formal sense, and it appears nowhere in 21 USC Chapter 9 (which is the legal text of the Food, Drug, and Cosmetic Act). If somebody can find statutory authority to the contrary, please provide the reference because I have looked and found none. The drug world is sufficiently complex, and the range of mechanisms of action so varied, that it would be extremely difficult to have a formal class structure. There are lots of medicines that come in regular dosing and with extended release dosing; Glucophage and Glucophage XR have different release characteristics, but both are based on metformin, both are considered biguanides, and each has a separate listing on formularies. Afrezza is labeled as "AFREZZA® (insulin human) Inhalation Powder" which provides plenty of leeway for a provider to decide that it is insulin, albeit with different PK/PD, and thus provide a no coverage or limited coverage decision.
|
|
|
Post by matt on Sept 22, 2017 10:24:21 GMT -5
Taking management at face value and combining it with what has been said about PGM rebates here seems to imply the rebates are structured so that PBMs get the rebates if X% of the prescriptions within the class of drugs are for the preferred one. If Afrezza is consider in a class of it's own then prescribing it doesn't put the rebates in jeopardy. Of course this could be an incorrect assumption. That is not how the rebates are structured. Remember that to be legal a rebate offer has to be a unilateral contract offered by one side as in "If you buy $XXX of insulin products from us in 2018, then we will pay you a rebate of 25% of your gross purchases". Note that a rebate is a promise to do something in exchange for an action, but it doesn't require the other party to purchase anything at all. Those constructing the rebate are marketing executives from competitors and they will structure the terms of the rebate however they need to in order to get the PBM to adopt the behavior they want. It is up to the competitors to think these things through, and rebates have been around in the pharma marketing arena since the 1980's so everybody knows how to play the game. No marketing executive ever wants to tell a major PBM that they aren't getting a rebate because they missed a volume target, and no PBM executive wants to tell their boss that they missed out on the rebate. Neither side is going to let Afrezza get in their way. There seems to be an assumption that if Afrezza gets an ultra-rapid designation then it will be the only product in a new class, but physicians do not prescribe based on class of drug. Afrezza is insulin, and whether you want to debate the differences with hexamers or not, most physicians don't look terribly close at formulation data. Afrezza for most physicians is probably viewed as "new and improved" way to deliver insulin, but it is not a separate category of therapeutics the way statins and PCSK9 inhibitors are entirely different ways to control cholesterols. Reduced hypos would be a very positive label claim, but there will still be a steep sales effort to drive change in established prescribing behavior.
|
|
|
Post by matt on Sept 20, 2017 16:09:22 GMT -5
Something like 5-10 Million is what I seem to remember once all the employee perks, executive perks and convertibles are taken into account.. That number is about right, or even a bit less than that with the most recent Deerfield deal. There are only two ways to raise significant new equity capital: 1. Call a special shareholders meeting and get the authorized share limit increased. That requires at least 21 days for the proxy solicitation and voting. 2. Use the 40 million in preferred stock. That is tied up at the moment due to the TASE listing, but as soon as TASE delists the company those shares can be used because they are already authorized (the TASE delisting becomes effective early November as I recall). Under Delaware law, the board can specify the terms for the "certificate of designation" for unissued preferred stock so it could give participation rights similar to 100 common or 1,000 common shares. The preferred could only be issued as convertible preferred if the authorized shares are increased.
|
|
|
Post by matt on Sept 18, 2017 15:34:19 GMT -5
Would the FDA not declare the distinction between ultra-rapid and fast-acting if the new class is made? Yes. If FDA wants to introduce a new class description, then they first have to define precisely what they mean by that new adjective, and secondly decide if Afrezza and/or Fiasp qualify. That first definition is critical because if, in fact, an ultra designation is commercially valuable then everybody else is going to want to have it and there must be clear, objective, quantifiable criteria for allowing or rejecting the claim by others. FDA will also have to decide what time difference is clinically relevant, which again has to be an objective and quantifiable measure. Personally, I think getting the FDA to declare a new class of insulins will be the hard part.
|
|
|
Post by matt on Sept 18, 2017 9:52:55 GMT -5
At the latest conference, I thought I saw a quote from Mike saying it would be in the next couple of weeks. That would imply the end of next week. But a CEO speaking in front of a crowd might just say "a couple of weeks" and mean "a few weeks". Mike is rather at the mercy of a third party. While FDA has time guidelines for any regulatory action, mostly they are not held strictly accountable. Sometimes the reviewers get behind schedule, and other times more discussion and debate is needed inside the agency than usual. In cases where the agency does have a hard deadline they will ask the company for more review time, but if the company declines to extend the review period then the usual result is a negative answer. I am sure Mike will make an announcement when he knows something, but for now the ball is in the FDA's court.
|
|
|
Post by matt on Sept 14, 2017 8:39:32 GMT -5
The restrictive and uninspiring label has been a major limiting factor. If almost nobody knows about a new drug, and you can only advertise claims supported by the label, then the consumer can't be blamed for not recognizing a better mousetrap. ^^^ This. The definition of "better mousetrap" is a highly subjective one, and most physicians don't take the time to read a label unless they have a reason to do so. The black box warning is enough to stop many physicians to stop reading on the first page because there are other alternative ways to treat diabetics that do not have a black box. You can argue all you want about various benefits of Afrezza versus the other RAI products, but the fact is that many physicians simply won't prescribe anything with a black box warning. The counter to that is publishing, lots of publishing, in peer-reviewed medical journals as that is where most physicians get their information. An author can write pretty much whatever they want in a medical journal, so long as they have data to back it up, and FDA cannot limit that publication. The fact that MNKD did not aggressively promote their product three years ago through a campaign of journal articles from opinion leaders and presentations at medical conferences limited their marketing interactions to what is on the label. The company is now trying to correct that by asking for different label claims but that is a difficult task. If the FDA had established standards for certain claims, such as "rapid acting" means evidence of a pharmacological effect within 30 minutes, but "ultra fast" means within 15 minutes, then the company would know exactly what data they need to present to FDA to get the claim approved. However, without a bright line, quantitatively defined benchmark, getting FDA to change the adjective might be like trying to nail Jell-O to a wall. You can bet that if an "ultra fast" designation is a commercially valuable claim than other companies will want the same label, so FDA will be cautious about giving the designation to one company unless they have first set a standard that others will have to meet. That is why regulators are such a pain to deal with when debating in the absence of clear standards.
|
|
|
Post by matt on Aug 27, 2017 16:21:53 GMT -5
Initial onset between Afrezza and lispro is about the same, but to say there is no difference is false. The area under the curves in the pharmacodynamics graphs are vastly different. Afrezza's area is much less than lispro's, hence the reason for the smaller likelihood of hypoglycemia with Afrezza. You will have to convince FDA that the difference in clinically relevant. The current label reads as follows: Absorption: The pharmacokinetic profiles for orally inhaled AFREZZA 8 units relative to subcutaneously administered insulin lispro 8 units from a study in 12 patients with type 1 diabetes are shown in Figure 3(B). The maximum serum insulin concentration was reached by 12-15 minutes after inhalation of AFREZZA 8 units and serum insulin concentrations declined to baseline by approximately 180 minutes. However, the faster absorption of
insulin from Afrezza [see Figure 3(B)] did not result in a faster onset of activity compared to
insulin lispro [see Figure 3(A)].
The reason you take a drug is to experience a beneficial pharmacologic effect, and the onset of that activity is not faster compared with lispro. I never said that Cmax did not peak earlier, it clearly does, but that does not make it a rapid acting insulin. It makes Afrezza a rapidly absorbed insulin. The company is trying to get the label changed to make the claim of ultra-fast acting, and that is not same thing as ultra-fast absorption. That is the hurdle they will have to jump over to get the FDA to change the label, and that takes data. However, I believe the other hurdle that will come along for any drug company asking for a label that says ultra-fast acting rather than rapid acting is to show that the difference is meaningful, which the FDA looks at as being clinically relevant. Making the case of exactly how many minutes before onset of activity is needed for a rapid label versus ultra fast label is new territory for FDA, which is why it will be difficult to get that on the label.
|
|
|
Post by matt on Aug 25, 2017 11:21:35 GMT -5
Vanguard filed a 13F-HR, which is a holding report. That report updates the market about how many shares an institutional holder owns as of the end of the quarter. It may reflect increases, decreases or no change from prior quarters. Taken alone, a 13F HR tells you nothing about activity during the period, you have to compare the numbers to earlier periods.
Also remember than an institutional investor only files once per quarter, and they file 45 days after the end of the calendar quarter. If Deerfield showed that they owned shares on June 30, they could have increased or decreased that position at any time after July 1, but they will not report again until November 15 when they will disclose how many shares they still held as of September 30. Institutional holding reports are a little bit like driving a car while looking in the rearview mirror; you cannot see what is currently happening. This is different from reports on Form 13D which must be filed within 10 days of the time when a shareholder acquires 5% or more of the stock of a company.
|
|
|
Post by matt on Aug 24, 2017 16:44:05 GMT -5
From the above-referenced Trial info:
"Estimated Enrollment: 46 Anticipated Study Start Date: September 2017 Estimated Study Completion Date: January 2021 Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)"
Why would what appears to be largely a 6 week study not be completed until 2021? Even the longest stated secondary outcome branch only goes out 13 months.
The summary didn't say that it would only be 46 patients; it said the initial cohort enrolled would be 46. This is a first pass through a Phase II study, and 46 subjects is fairly typical for a first Phase II trial, but it will not be enough to satisfy the safety concerns. Expect to see the 46 patients enrolled, then the study will shut down while data is analyzed, and then it will restart with more subjects and a revised protocol that addresses anything unusual seen in the original cohort. That larger group will have much more statistical power and will allow the company to propose different language for the pediatric population, but don't expect to see those revisions until some time in 2021. This will not be a quick process. FDA is very tough on changing label copy and will demand to see compelling data, including absence of adverse events in the original cohort that elect to continue use beyond the initial period. It will be much the same with the other label changes. The FDA based the original wording on the data that Mannkind provided from the original registration trials, so to get that label changed there must be overwhelming evidence that FDA got it wrong the first time. Similarly, with respect to describing Afrezza as "ultra rapid" I don't know that anybody has shown that the rate of absorption is clinically relevant because the onset of activity is the same as lispro. FDA is not going to sign off on a new adjective unless the company requesting the designation shows that there is a meaningful difference to the patient, and I don't think Mannkind has the necessary data because they have not run any large studies since the drug was approved. A limited bridging study on PK alone is not going to be enough. It is up to the company to prove that something is true, it is not up to the FDA to disprove it. Since the default position of the FDA is that nothing is true unless proven to be true, that is a difficult negotiation posture for any company without a ton of data to back up their new claims.
|
|
|
Post by matt on Aug 24, 2017 6:21:14 GMT -5
with their huge compensation packages, if they sell 300 shares, the optics are better if they buy 600 a week before or the day after the sale. There is no rule against that I see. There are rules that prevent that if the person is an insider. Just like an insider cannot load the boat right before announcement of good news, or sell just before bad news, there are blackout periods around any material event. Note that it doesn't matter if you know there is material news coming, only if the executive does. I think we all know that there will have to be a material event or a major fund raising in the near term and any executive that knows about those plans, or even the options under serious consideration, would be tainted by that knowledge. Automatic sales pursuant to an established plan, like tax selling, are exempt from the rule but selectively buying shares to offset the tax sale are not exempt. The executives could file a 10b-5 plan with specific rules of what will be bought (like buy 10,000 shares on the first trading day of every quarter) but this is commonly done with sales and rarely done with purchases. Part of the reason is that taxes depend in large part on the PPS, while a purchase plan is more difficult to calibrate the program to market events.
|
|
|
Post by matt on Aug 23, 2017 11:32:25 GMT -5
I am not sure the 18-49 age group is the most relevant if you are after Type 2 diabetics. Are there numbers for the older viewers? Advertisers have access to this data; it isn't generally available. If you want to know how many left-handed, Protestant, women, aged 30-45, with a preference for German cars watched a certain show then A.C. Neilsen or another marketing company can break it down for you. Advertisers pay for a certain types of eyeballs which is why Neilsen ratings are so important for a show; it determines how much commercials will cost. To Thall's comment, most Internet advertising doesn't cost anything unless the banner or link is clicked. How much that click costs depends on who else wants to advertise to the same audience. The top three links on any Google search are paid links and the rankings depend on how much the advertisers bid for specific keywords and the quality ranking of the site. That makes it a little unpredictable because you might assume that you can run a campaign at ten cents per click, but then a competitor can jump in front with a bid of eleven cents and they will get a better ranking. There are robots constantly analyzing the data and the current bids, tweaking ad placement and prices in much the same way as airlines tweak reservation pricing as certain flights fill up. Some words cost a fraction of a penny per click while others cost more than $100 per click! Afrezza would be a cheap key word because only Mannkind would want to promote their brand name. A more generic term, like insulin, would have lots of competitors and in an advertising price war with Lilly or Novo the little guys will surely lose. There are few ways to game the system since Google is very good at extracting value from their search engine.
|
|
|
Post by matt on Aug 22, 2017 6:58:05 GMT -5
Maybe this is why we paid Haken hush money for so long. That was very interesting how they had to file information and keep it secret from the public for 2 years. Anybody care to guess what secrets MannKind is keeping with this fileing? No need to wonder, just go to the referenced 10-Q on EDGAR, open the exhibit, and see what has been redacted (search for strings of "****"). Both of these were redactions of pieces of the Sanofi agreement, one covering international markets Mannkind wanted to exploits (probably Israel) and one covering specifics on the Alphastar insulin supply agreement. There have been other contracts that have redacted pricing information on Alphastar, royalty rates and milestones on the RLS agreement, and terms of the rental abatement period for the new office. All of this is typical commercial practice when a business partner doesn't want their pricing information out in the public view. As for Hakan, most executive employment agreements have confidentiality provisions that survive termination for some years. There is no need to pay a retired executive to keep his mouth shut; that is what the severance payment is for. Don't get your knickers in a twist over this kind of stuff. Learn to research via EDGAR and you can find definitive answers to almost everything you wonder about. Unless a company is wildly deficient in SEC reporting, there are not many secrets that a diligent shareholder cannot discover by simply reading the filings.
|
|