Author’s reply » The advantage for technosphere with pain medications also lies in the speed with which the drugs it binds becomes active. Very fast pain relief would be an advantage.
But if I understood some of the wording used in the presentation, it may be that they are looking not only for an effective application but one that could be brought to market in a reasonably short time frame.
Author’s reply » I have been following diabetes for more than 15 years, and over that time almost all the diabetes drugs that have been introduced have ended up having far more significant side effects and far less efficacy than the drug reps claimed. Adoption of untested new drugs has been far too swift, and they have replaced safer, cheaper drugs, often contrary to the accepted practice guidelines.
So over all, I think it is good, not bad, that access to the reps has been limited. There is a lot more money marketing SGLT-2 inhibitors and the proliferating ranks of me-too incretin drugs than could ever be apportioned to Afrezza.
Fortunately, what Afrezza has going for it, unlike all the rest of these competing new drugs is that it has an instantly understandable unique selling proposition that does not require that salespeople sell it with the exaggerated and often fraudulent claims made for so many other new diabetes drugs over the past 2 years. (All of you who were told that Avandia would regrow your beta cells raise your hand. All of you who found out that the only cells it really grew were new fat cells that persisted long after you stopped the drug, raise yours. )
MNKD expects they will be reporting less spending on the factory by the 2nd quarter of 2015, and overall less expenses, though there will be some new R&D expenses for non-Afrezza products--i.e. new Technosphere applications.
Edstrom said they are currently working with a consulting firm to determine the very best applications to apply the Technosphere technology to next. He concluded the session by stating that by February they hope to be able to give much more detail about the next application(s) of the Technosphere technology, and that they are hoping to be able to announce a signed contract by then.
Author’s reply » If Afrezza is most successful, the reps will be marketing the heck out of it.
What I have seen happen with these diabetes drugs is that the companies stop marketing the ones that aren't selling well pretty fast--sometimes too fast, as seems to have been the issue with Sanofi's Apidra.
They only have a very small amount of time to spend with the doctors, a lot less than they used to, and many doctors no longer take free samples as the paperwork involved with them has skyrocketed. So they have to have something really punchy to say in those few moments they have to work with, something that will result in more prescriptions being written.
Afrezza is brand new, and it's legitimate to ask doctors to spend a little time learning about it. Because it's going to be a while until their Lantus successor, Toujeo, is approved, Sanofi really doesn't have a whole lot else to talk about with doctors that treat diabetes right now. So reps are going to be very glad to be able to do sales visits focussing entirely on Afrezza.
In another year, when Toujeo might (or might not) be approved, it would be expected that the marketing of Afrezza would relax some, as it will be becoming clear whether or not it is taking off. If Toujeo is hitting the market, (or some other drug that could be discussed in the same sales call) realization of this would be reflected in the budgeting for expenses that was discussed.
Pfeffer made it clear that MNKD has an equal voice in the committee that sets the budget for expenses--which includes those attributable to marketing.
The upcoming Afrezza launch was discussed at some length. Edstrom stated that marketing partner Sanofi (NYSE:SNY) is going to be marketing from the start to both general practitioners (NYSE:GPS) and endocrinologists, with a heavier focus on the endocrinologists, especially the top 10% of heavy prescribers and those known to try new drugs.
However, because the companies believe that there will be strong patient-driven demand for this product, Sanofi is going to also make sure that GPs are aware of Afrezza and ready to cope with patient requests for it.
Edstrom stated that the belief is that Afrezza may be attractive to GPs because it will be easy enough for them to prescribe that GPs won't have to refer patients out to Endos and lose them as patients, which is what currently happens when patients start fast-acting insulin.
Asked how MNKD can be sure they won't be charged for the expenses of Sanofi sales reps making visits in which they promote their other drugs, rather than Afrezza, the MannKind representative replied that the costs of marketing are apportioned according to the success of the products being marketed. So if Afrezza isn't getting pushed, and isn't selling, MNKD won't be paying for those calls.
It was also pointed out that the budget for marketing Afrezza is set by a committee on which MNKD has equal weight with SNY. So MNKD will have the ability to make sure that neither too many nor too little resources get apportioned to Afrezza.
One thing that should be pointed out first and foremost is that these shares sold were part of a scheduled insider share sale under the formal Rule 10B5-1 Plan.
Diane Palumbo, Vice President of Human Resources, sold some 183,522 shares on December 1 at a volume weight average price (VWAP) of $5.8943, for just over $1 million in total proceeds. She still has 29,105 shares.
Hakam Edstrom, president, sold some 74,668 shares on December 1 at a VWAP of $5.8937 per share, for a total of about $440,000. Edstrom is shown to have 1.047 million shares remaining.
The logic over insider selling is far more complicated than open market share purchases by corporate insiders. The insiders may be doing estate planning, they may be buying a house or there may be myriad other reasons. Again, these two insider sales were under a Rule 10B5-1 Plan, so they are likely less than ominous on the surface. Still, with MannKind shares having been cut in half, and with so many skeptics fighting optimists here, it is easier to see why some investors might wonder about large blocks of stock being sold.
MannKind: Strategy, Accounting, And Technosphere At Piper Jaffray Healthcare Conference
Amphstar said on their call today, That they became instantly profitable based on the deal they made to supply insulin to mannKind. I missed part of the call so I don't know if they talked earlier about that purchased by mankind but I thought it was good that it was mentioned about their profitability was based on their contract and future sales to MannKind.
I went back and listened to the call again. They said that they had 9 billion in the pipeline on generic products using their inhalation side of their business. They particularly stated that they were working on PARTICULE ENGINEERING of complex molecules. They view their inhalation side of the business with a higher value. That Amphstar would do the science side and that a Pharm partner would do the sales and marketing side. Makes me wonder if they are going to use the Technosphere on some generic drugs. I would encourage you go listen to the call and give your opinion. I found the call interesting. this part was in the last 7 or 8 mins of the call.
PJ Conf 12/2/14
Pipeline Full of New Diabetes Drugs Presents Challenge to Health Plans
A report from the Pharmaceutical Research and Manufacturers Association (PhRMA) says there are 180 new medications in the pipeline for type 1 and type 2 diabetes. That number reflects the boundless therapeutic and market opportunities diabetes offers to pharmaceutical companies.
More than 19 million people in the United States have diagnosed diabetes and 7 million more have the disease without being aware of it, according to the Centers for Disease Control and Prevention. Current trends foreshadow that by 2050, 1 in 3 may have diabetes — the confluence of an aging population, increasing numbers of high-risk minority groups in the population, a longer lifespan, and reduced mortality attributable to diabetes. Today, as many as 79 million people may have prediabetes.
Diabetes is a “blue sky” opportunity because a magic pill has not been found. There are multiple classes of antidiabetics, but only about 8 million Americans have their diabetes under control. Patients respond differently to the medications and have comorbidities that require more treatment options. There is still a need for long-acting agents that achieve glucose homeostasis and that reduce dosing frequency and injections.
There are also opportunities for niche drugs like Afrezza, an inhaled insulin, which has just cleared regulatory hurdles. Delivering insulin to the blood-rich lungs speeds its entry to the bloodstream, sparking rapid glucose control.
The limitations of the diabetes medications on the market today present both a challenge and an opportunity for health plans. The challenge lies in devising formularies that provide access to the best medications and simultaneously control costs. The opportunity lies in improving medication outcomes and reducing the total cost of care.
The drugs in development span the gamut of mechanisms of action and also pursue new avenues. The more prevalent agents in development are insulins and those focused on improving pancreatic alpha- and beta-cell functioning.
The loss of beta cells is the primary cause of diabetes, and existing medications largely focus on controlling blood glucose after beta-cell demise. There is now an emphasis on drugs that target the core regulatory function for blood glucose. Homeostasis is governed by two hormones, insulin and glucagon, both secreted by the pancreas. When blood glucose levels are low, alpha cells in the pancreas secrete glucagon, which triggers the liver to release glucose into the blood. When blood glucose levels are high, beta cells in the pancreas release insulin, which triggers fat and muscle cells to absorb glucose from the blood, thus returning it to normal levels.
“Medicines in Development: Diabetes,” a PhRMA report, identifies stem cell research among recent research activities and discoveries that may lead to new treatments. Researchers at Harvard have discovered a hormone that stimulates production of insulin-secreting pancreatic beta cells. In London, scientists have manipulated stem cells into becoming insulin-secreting cells. And in Australia, researchers have isolated stem cells from the pancreas and turned them into insulin-producing cells for type 1 diabetes.
Drug development efforts also focus on combination agents and long-acting agents that offer the potential to improve adherence and homeostasis.
Current meds don’t measure up
There is a need and opportunity for new medications because individually, current antidiabetics do not control diabetes in most patients.
“Look at the reduction you get from most individual antidiabetics except for insulin,” says Brian Solow, MD, chief medical officer at Optum Rx, a PBM subsidiary of United Healthcare. “You may see an average reduction of 1% or slightly higher across the classes. But doctors see patients who come in with HbA1c levels above 9%, so you have a long way to go.”
Brian Solow, MD
“Because of the evidence of vascular benefits, we are seeing increased use of second- and third-line agents,” says Brian Solow, MD, chief medical officer at Optum Rx.
The 2014 American Diabetes Association (ADA) guidelines say, “Comparative effectiveness meta-analyses suggest that overall, each new class of noninsulin agents added to initial therapy lowers HbA1c around 0.9–1.1%.”
However, new drugs will have to carve out roles for themselves. The clinical guidelines from the ADA and others have clear treatment algorithms. In addition, health plans have their own programs for managing diabetes and new medications will have to demonstrate their efficacy and value.
Plans given latitude
Current ADA guidelines include a diagram of the therapy algorithm, starting with metformin monotherapy, then progressing to two- and three-drug combinations. It is a true Chinese menu, allowing for open selection of a sulfonylurea, thiazolidinedione (TZD), DPP-4 inhibitor, GLP-1 agonist, or insulin. The ADA does not prefer one class over another in combination therapy, leaving it up to clinicians to determine the safety and efficacy of each drug in each patient. Open choice also gives health plans some latitude in designing their formularies and utilization management programs.
The ADA treatment diagram helps in selecting add-on agents by listing the effect of different classes on HbA1c reduction, the risk of hypoglycemia, weight gain or loss, major side effects, and cost.
Physicians appear to be following guidelines more closely, thus creating a possible barrier for new agents. “Physician behavior is changing, in part because there are guidelines from so many different organizations,” says Solow. “For example, doctors have finally figured out that you’re supposed to use metformin as the first-line medication.”
“We keep a close eye on utilization, and metformin is the driver in first-line treatment,” says Daniel McConnell, PharmD, clinical coordinator at Geisinger Health Plan.
Daniel McConnell, PharmD
Physicians are trying two or three oral drugs before turning to insulin, says Daniel McConnell, PharmD, clinical coordinator at Geisinger Health Plan.
“Today physicians are more interested in driving toward HbA1c goal levels,” says Solow. “I can remember when patients would be on medications for years and their HbA1c would remain elevated and unchanged,” says Solow. “Now physicians are taking more responsibility for driving A1c levels down because of the evidence of the vascular benefits, so we are seeing increased use of second- and third-line agents.”
The add-on medications are a sulfonylurea, TZD, DPP-4 inhibitor, GLP-1 agonist, or insulin. Health plans are using several different techniques to manage two- and three-drug combination therapy.
“We have step therapy on many of the second- and third-line agents,” adds Solow. “We allow the use of DPP-4s or GLP-1s when that is appropriate, but we want to see a history of the use of the first-line agents.”
“As we review what physicians are doing, it seems they’re sticking to two or three orals and then finally using insulin,” McConnell comments. “We don’t see much differentiation in the efficacy of the sulfonylureas, the TZDs, and the DPP-4s. That’s why we steer as many patients as possible to metformin, and then if they are resistant to insulin add on a sulfonylurea or a DPP-4. If people have progressed to a point where they need three orals, we try to get as many of them to insulin as we can.”
A complex disease to manage
Solow points out that managing diabetes is more than managing existing and new medications. “Broad-based clinical programs are important,” he says. “Diabetes is still very fluid because of the large number of patients and the complexity of the disease and its relationship to comorbidities. The management of diabetes medication therapy is very involved.
“Adherence is a real problem — you have to be sure you are running a very thorough adherence program,” adds Solow. “Then the accompanying disease processes such as cardiovascular disease, and the appropriate use of ACE inhibitors and ARBs in patients with nephropathy or hypertension, are important. According to the new guidelines, making sure patients are on a statin is also important. Our focus is to work with our customers and take advantage of the data that we can provide in identifying diabetes patients and informing them about their needs for medication therapy.”
Their recent bear raids appear to have been rather costly to them. On November 16, they drove the price down on 975,000 shares in several minutes, only to see it recover on a mere 150,000 shares or so. This repeated again on Nov. 28. MNKD went down on big volume and back up on much smaller volume. Meanwhile, as the shorts play out this questionable strategy, the short position keeps increasing and the share price has been firming up. The shorts have also been paying huge interest to borrow shares and have been seeing quite a few of their LEAPS expiring as money losers or even worthless. It is also obvious that the accumulating institutions do not appear to be bothered by this nonsensical maneuvering being conducted by the shorts. The institutions are probably quite happy with the 12.5% interest they are getting from their loaning shares. I for one do not believe that the shorts know something that Sanofi and their institution buddies do not know. It is my opinion that the shorts have gotten themselves into a very unfavorable situation at this point and are struggling to find an exit strategy. It's going to take quite a while for those 82 million short shares to disappear.
Other newly approved FDA drugs are automatically placed on the Tier 3 drug copayment level if used to treat a covered medical condition
Self-injectable and other high technology drugs which are newly approved by the Food and Drug Administration (FDA) are automatically placed on the Tier 4 drug copayment level.
new drugs are placed initially in Tier 3 with the possibility of a status change to Tier 2 later on.
"In general, AFREZZA's clinical date and drug attributes were viewed very favorably. Payers told us that they believe the elimination of injection would be an important compliance advantage and due to the chronic nature of the diabetes there would welcome a product of increased compliance within the diabetic population.
Now the message from the payers if that they see our AA as the value and price compare for AFREZZA based on the current safety and efficacy profile as well as their precede advantages of convenience and even increased compliance associated with our mode of delivery.
This is important because, pens already carry a price premium due to their convenient and compliance benefit compared to needle injections, and based on this research, we have a clear understanding of how we can drive the placement of AFREZZA on Tier 2 formulary status which is important to drive volume and revenue and of course the most important value of AFREZZA is the far better kinetic profile leading to improved medical care and better outcomes. Since completing studies 171 and 175, we have also updated our market research into physician interest in prescribing AFREZZA which could be the first ultra rapid acting insulin in the market."
Afrezza is covered by PBM CapitalHealth, Jan'15, pg24
It's possible that the final pricing from Sanofi could move Afrezza to Tier 2 but it looked as if many other new diabetic drugs are also in tier 3:
Victoza, Bydureon, Byetta, Farxiga, Invokana, .....Billions were made with Victoza, so even if we are a tier3 classification, I think people do not mind a little more co-pay and we would be fine. After all, I think people take Victoza to avoid insulin injections so I think we could also see some sales from Victoza patients switching over to Afrezza. I trust Sanofi to know the diabetes market space to set the best pricing for both maximum margin and acceptable cost to patients.
It would seem much work is in place for an early 1st quarter roll out as oppose to a late 1st quarter based on MNKD production start in early November. My hope and guess would be for 1/15/15 launch. This would give MNKD a good 2 months time to produce and stock pile the 4 & 8 insulin cartridges.
I would not worry about Afrezza being a tier 3. Advair for asthma is tier 3 and had sales of over $5 billion this year. It just has a higher co-pay.
This from the same site.
The Tier System
All FirstCare plans include a tiered structure for our prescription drug benefits. A brief explanation of these tiers is below:
Tier 1 – Lowest out-of-pocket cost for your generic drugs
Tier 2 – Higher out-of-pocket cost for a limited list of brand name drugs
Tier 3 – Higher out-of-pocket cost than tier 2 for other brand name drugs
Tier 4 - Immunosuppressive medications, chemotherapy and associated agents, injectable drugs, medically infused medication, and high technology drugs.
It would seem as if Tier 1 is for generic drugs, but I don't know if there are exceptions to the rule.
Another Afrezza killer app is Obesity. Mnkd could expand A label the same way Novo expands Victoza.
Victoza - Novo Nordisk
October 2, 2013
Launch Date: February 2010 (U.S.), July 2009 (EU)
First-Year Sales (2010): 2.3 billion kroner (about $418 million)
First-Half 2013 Sales: 5.555 billion kroner (about $1 billion)
Analyst Estimate for 2018: $4.07 billion
Over Victoza's short history, earnings headlines have featured one impressive growth stat after another. Last year, the diabetes drug's sales prompted Novo Nordisk ($NVO) to hike its financial forecasts not once but twice. And that's after it more than doubled sales in 2011, to 5.99 billion kroner, or about $1.04 billion at the time--just past the blockbuster threshold. It was the drug's first full year on the market in the U.S.
Victoza is a GLP-1 agonist, competing directly with Byetta and Bydureon from Bristol-Myers Squibb ($BMY) and AstraZeneca ($AZN), and with Merck's ($MRK) DPP-4 inhibitor Januvia (and to a lesser extent, Onglyza, from BMS and AZ, and Tradjenta from Eli Lilly). Novo has put serious money behind studies comparing Victoza with several of its rivals, and, luckily for the company, Victoza has come out on top.
Victoza ended 2012 at 9.5 billion kroner (about $1.7 billion), only about two-thirds more than the previous year. So, growth has slowed somewhat. It slowed further this year, with first-half sales at 5.56 billion kroner, about $979 million at the time. That was 30% growth year over year.
Part of the reason that Victoza has continued to churn up growth for Novo is that the Danish drugmaker expanded its U.S. sales force last year, in anticipation of winning FDA approval for its latest diabetes fighter, Tresiba. But that approval wasn't forthcoming, so the new staff went to work promoting Victoza and Novo's modern insulin products. That, in turn, helped Victoza grow its market share to 65% in the GLP-1 field.
Until last month, that is. The company lost a big Victoza contract with the pharmacy benefits manager Express Scripts to GLP-1 rivals Byetta and Bydureon. Analysts estimate that the PBM's business accounted for 15% to 20% of Victoza's U.S. sales. That could put a $100-million-plus dent into 2014 results.
Meanwhile, Sanofi ($SNY) won approval for Lyxumia, another GLP-1 drug, which is taking aim at Victoza. Longer term worries include Lilly's experimental drug dulaglutide, which could win approval by 2015.
But Novo has ideas that could put Victoza in the fast lane again. For one thing, the company recently filed for European approval for IDegLira, which combines Victoza's active ingredient with insulin degludec, a.k.a. Tresiba. Recently released data showed that the combination therapy beat Victoza and Tresiba at pushing blood sugar levels lower.
In clinical trials before its debut, Victoza patients lost more weight than patients taking comparator drugs. It was a "value-added benefit" noted by some researchers. So, Novo has since been testing Victoza as a weight-loss remedy, and the company plans to ask regulators to approve a new weight-loss indication by the end of 2013. Market researchers figure Victoza could quickly dominate the obesity market, given the slow starts for the two new weight-loss drugs approved last year, Vivus' ($VVUS) Qsymia and Arena Pharmaceuticals' ($ARNA) Belviq. Company executives are more circumspect. "I'd like to get the approval first," CEO Lars Rebien Sørensen told FiercePharma in August.
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