This quote from you totally proves you don't, won't or don't care to know the benefits of Afrezza.. "They care only about the price and risk-benefit of Afrezza relative to injectable meal-time insulin." Every take shots in a restaurant before meals?? Read The Reason Why It's Superior to RAA's out there today. You, Karp, Cramer, can keep trying to help your short pals, Your running out of time.
1. AFREZZA's Ultra Rapid Action is nearly an exact mirror to the endogenous post prandial insulin spike in a healthy non diabetic body, and as such it enters the body quickly and is active during the correct time frame to handle the meal time spike in blood sugar
2. As a physiologic meal time prandial insulin it is even more critical that it does its job and then rapidly exits the body without leaving behind a long insulin "tail" that leads to dangerous drops in blood sugar/hypoglycemic events, and insulin stacking problems. The currently available prandial insulin products, even the "rapid acting" insulins such as Humalog and Novolog are way too slow and linger for way too long after meal time digestion is over. This leads to these currently available insulins transitioning from prandial insulins to becoming "more basal" insulin. This effect does lower HbA1c levels making them appear more efficacious to the ignorant/uninitiated, but that IS NOT A GOOD THING (though the closed minded FDA staffers would have us believe otherwise)! HbA1c as a long term average is a very poor and incomplete statistical measure for quantifying how you are managing your diabetes. The trials for AFREZZA heavily relied on HbA1c endpoints whilst discounting more important measures such as fasting blood glucose levels, time spent in target range, leveling out blood sugar levels with higher lows and lower highs, reduced weight gain, less hypoglycemic events, etc...
3. Defensive snacking is largely eliminated with AFREZZA leading to weight loss, there is no longer a need to "feed the insulin" or face the risk of immediate coma or death.
4. Complex mealtime titration is not necessary due to the PK/PD of AFREZZA. This is huge for patient convenience and compliance
5. Constant finger pricks for blood glucose monitor testing is greatly reduced due to the PK/PD of AFREZZA. THIS IS A HUGE BENEFIT that the FDA has completely ignored. This is yet another way that the real world use of AFREZZA helps the patient move away from being a human pin cushion!
6. AFREZZA has absolutely zero side effects for the vast majority of patients, and very very minor side effects for a tiny minority of patients, such as a minor cough that quickly goes away as you adjust to inhaling the medicine. This drug is very safe, and very effective. In fact AFREZZA will be one of the safest and most effective drugs the FDA will ever approve.
7. AFREZZA will be (by orders of magnitude) the best insulin product on the market for making between meal adjustments for all diabetics across the spectrum of the disease. Currently available prandial insulins are far too slow. AFREZZA allows us to live in real time for the first time. Even patients who choose not to use AFREZZA as their everyday bolus, will NEED to have this product at their disposal for just this reason.
8. AFREZZA is the only prandial insulin with the Ultra Rapid Action needed to close the loop for the artificial pancreas. It's the missing piece that allows this project to move forward.
9. The unique and novel PK/PD of AFREZZA allows the patient to know their blood sugar levels are safe when they go to bed and not fear dying in their sleep as occurs with currently available products.
10. Patients on AFREZZA have far less blood sugar extreme highs and lows which lead to a myriad of health problems: blindness, organ failure, amputation, coma, death.
11. AFREZZA will be the first and only Ultra Rapid Acting insulin.
12. AFREZZA is easy for anyone to use, even the elderly and young children. The device is a marvel of modern design, small, efficient, and effective. Simple to use, inexpensive and disposable, few moving parts, you don't even have to break it down and clean it! This is exactly the type of revolutionary product that the FDA needs to make available to the public
13. Approval of AFREZZA opens up the Technosphere drug/device platform for pharma development for many other innovative products to come such as pain relief medicines and vaccines. This is the type of innovation that the United States needs to remain the world leader for, lest we by surpassed by companies in other countries, and we are forced to watch the United States take a back seat.
14. AFREZZA breaks down every barrier that physicians and patients face in initiating insulin therapy: 1. Needles, 2, Weight Gain, 3. Fear of Hypoglycemic Events, 4. Complicated Educational Process, 5. Gaining Patient Compliance
15. Research indicates that AFREZZA slows the progression of the disease. More studies are necessary for a final verdict, but wow--what a benefit!
Do We Really Need Ultra-Fast Acting Insulins?
Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia
Consultant: Novo Nordisk, MannKind, Medtronic, Sanofi
• Speaker’s Bureau: Lilly, Novo Nordisk, Medtronic, Sanofi
• Grant and Research Support: Biodil, Lilly, MannKind, Medtronic, Sanofi
Afrezza is mentioned 17 times on pages
19,45,48,51,52,53,54,55,56,58 of 62
You guys are too harsh on Mnkd and Sanofi mgmt. They're doing a phenomenal Afrezza launch job behind the scene. No wonder Pipper Jaffray Top 15 2015 Bio Pharma Suprises lists "Mnkd/Sny launch goes well" at #6. Since I am working my butt off too, Longs or Shorts, can you promise to read 62 pages in their entirety before replying? They deserve your undivided attention.
Big things I saw:
Section 4.2: looks like sanofi is on the hook for all regulatory costs (does this means the clinical study costs?) doesn't appear to be a cost that is split 65/35
Section 6: while milestones aren't listed there's some good outlining here.
What's really interesting is that there's a milestone listed that is redacted and is neither manuf, approval or sales driven. So, this must be milestone bonus related to inhalable glp-1.
Note that the 3Q14, 10-Q didn't mention about inhaled GLP-1.
However, 2Q14, 10-Q, pg 43:
"Under the terms of the Sanofi License Agreement, we granted to Sanofi a right of first negotiation in the event we propose to grant to any third party a license to develop or exploit an inhaled glucagon-like peptide-1 agonist. In addition, if our board of directors determines to pursue a change of control of MannKind, we will be required notify Sanofi of such determination within a certain period of time so that Sanofi may, at is discretion, negotiate with us for a potential acquisition of MannKind by Sanofi"
MannKind Corporation MNKD 5.39% shares are trading higher $0.28 at $6.03 in Monday’s session. The rally is being attributed to a First Call rating upgrade earlier this morning.
The recommendation is accompanied by a $9.75 price target, according to 9 analysts in consensus.
The issue, which has had many false starts in the past, is back above $6.00 for the first time since November 28, when it ended that session at $6.15.
With a short interest of nearly 22 percent of float, any positive developments on the research and development front may ignite a furious rally.
It's possible the Street is anticipating some much-needed good news regarding the company's rapid acting inhaled insulin drug, Afrezza.
Joel Elconin , Benzinga Staff Writer
January 26, 2015 3:28pm
according to CFO Matt Pfeffer, who discussed Mannkind’s manufacturing strategy at a recent investor conference.
“We didn’t fully build [Danbury] out because it's quite expensive to do so, pre-approval, but the facility is scaled to do up to two billion cartridges per year fully built out,” he said at the Jefferies Global Healthcare Conference earlier this month. However, the biggest bottleneck to scale-up is fill finish capacity, he added.
“At launch, we expect to have three of those fill finish lines in place, which should give us about 375 million per year capacity.”
He continued: “We can add capacity in a very nice relatively rapid modular way, which is one of the advantages of having built this very nice expensive facility with all the clean rooms and things in place, just waiting to drop the machines in.”
Afrezza is based on Mannkind's Technosphere technology, which uses the excipient fumaryl diketopiperazine (FDKP) as the particle matrix to carry recombinant human insulin to the lungs. The product is inhaled from the cartridge using a device described by Pfeffer as looking a "little bit like a whistle in use," powered by inhalation alone.
Wells Fargo Healthcare Conference Call
June 17, 2014 10:00 AM ET
Matt Pfeffer - Chief Financial Officer
Slide about commercialization, needless to say, we do expect to commercialize this product with product manufactured by us out of a facility we've already built in Danbury, Connecticut. It’s not fully built out yet, there is a lot of room sitting vacant waiting for a fulfill and finish equipment being put in; what we expect to launch was about a quarter ultimate capacity, some 375 million to 400 million cartridges, that capacity increases as you added the newer machines, but we expect ultimately that that facility was designed and scaled to accommodate 12 fill and finish lines so we'll launch will 3 and we’ll install the other ones as needed but it was designed [inaudible] fairly quickly as the demand goes up. But ultimately we can do 2 billion cartridges a year out of that facility, which is pretty good number and we'r
Trading Biotechs From His Bedroom Nate Pile Beats The Street
For the rest of the Forbes 2015 Investment Guide, click here.
Nate Pile, 45
Day Job: Newsletter Editor, Stay-At-Home Dad
Strategy: Technology and Biotech Investing
Ten-Year Average Return: 17.6%
Top Pick: MannKind
As a math major at UC Berkeley in the 1980s Nate Pile’s awakening to the stock market came quite literally every morning at 6:30 a.m., when his college roommate, an active trader, got a call from his broker at the market open in New York City. The bull market of the 1980s hooked Pile, who landed a part-time job stuffing envelopes at one of the top-performing investment newsletters of the day, Jim McCamant’s Medical Technology Stock Letter.
Pile launched his own investment newsletter, Nate’s Notes, in 1995 from his bedroom, but for eight years he needed to teach junior high school math during the day to pay bills. Today Pile’s newsletter, focused on biotech and technology, is still headquartered in his home, in part because he is caregiver for his two daughters, but it is also one of the top-performing of its type, according to Hulbert Financial Digest. Ten-bagger recommendations of biotech giant Celgene and Apple have given a big boost to Pile’s returns.
Strategy: Pile pays attention to traditional fundamentals and technicals, but because some of his picks are biotechs he doesn’t fixate on traditional metrics. To understand the “story” of a stock, he drills down into the minute details found in the financial statements of the companies he is following. His portfolio tends to be concentrated, holding only 20 stocks. According to Pile, the key factors in his decision to invest are whether the company has a game-changing product that has the potential for huge growth and whether he would be happy to own the company even if the stock market didn’t exist.
Best Idea: Pile likes biopharmaceutical MannKind of Valencia, Calif., trading $3 below the level at which he first recommended it. In June the company finally received FDA approval for an inhaled diabetes treatment called Afrezza, but the stock is still down 60% from its 2004 IPO. Pile says many investors lost hope after Pfizer pulled a similar drug from pharmacies because of weak sales. Yet he points to two crucial differences: Pfizer’s product was the size of a liter bottle and MannKind’s the size of a lifeguard’s whistle. More important, Afrezza works faster, thus giving patients more control.
It's actually pretty marvelous," Houghten said. "You can't (overdose) on this drug."
The drug is being developed in partnership with Mannkind Corp., which has created a small device that allows people to inhale medicine. By inhaling, the medicine can relieve pain quicker than through pill form, Houghten said.
"Our pain compound, if it all works out, ... if you can take that pain compound and just inhale within just 30 seconds to a minute, your pain will be alleviated," Houghten said. "So you can see that that can be a real important step."
The drug has been tested on two separate animal groups and Houghten said the drug will be tested on a third before going before the U.S. Food and Drug Administration, which must give approval for human trials.
Houghten said the unique nature of the drug could make it easier to get approval.
"You never really quite know," he said. "Right now, everything's looking really good. ... We can't get a high enough dose that causes a problem."
Patients also do not build up a tolerance to the medicine, whereas other pain relievers require patients to take more and more to get the same effect.
Houghten said he is thrilled with the drug's progress.
"In reality is if it's 2014 (before human testing), I'm still going to be happy," Houghten said. "I don't think it's going to be a problem with the FDA. It's very simple what we want to do, so we can show them clearly here's the effective dose, here's the toxic dose. That's 90 percent of it right there. It's effective and it's not toxic."
11 minutes ago
liane, saxcmann and 1 more like this. Quote
Just brought home a box from my local pharmacy, ordered it yesterday around 3pm.
Have waited 11 ½ years for this.
Can’t believe we are still at $5, but we made here! So now what, I guess I open it?
Read more: http://mnkd.proboardsDOTcom/thread/1625/brought-home-box-local-pharmacy#ixzz3PnF6FMlU
Matt: "However, our technology platform certainly has a lot of applications even beyond diabetes, where we think that we can grow with the product and pain management being one of that because of the PK/PD profile of Technosphere and of the inhaler that we have.
And we are looking into a number of others development opportunities for our technology platform. And we are putting kind of significant effort into right now to determine what are the next opportunities where we can leverage this platform, beyond working also in second-generation ideas for AFREZZA and product AFREZZA. And actually even working with other companies that have seen what our technology can offer in terms of product development opportunities."
The next Technosphere product will be the Cricket for migraine Pain.
It has been in preliminary trials at Torrey Pines utilizing lab mice.
Mannkind management believes that the Cricket for migraine pain will be bigger than Afrezza.
In U.S., more than 37M people suffer from Migraine. Generic sumatriptan delivered via nasal spray is still restricted. Al has known this for years.
"My wife gets terrible migraine headaches and uses GSK's Imitrex to treat them. However, if the migraine goes too long without being treated, then the drug doesn't work as well. It would be a home run for Migraine suffers to have something that works in 5 minutes vs an hour." Partner will be GSK.
Hard to take an anti-nausea ZOFRAN pill when you can't keep the pill down. Also made by GSK.
PA: "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."
SNY also lic'ed TS for inhalable GLP-1. 2 TS partners will be announced: GSK, SNY.
After bolting 93% higher already this week on a positive ASH update, bluebird bio (NASDAQ: BLUE) is continuing higher Friday (+2.3%) in part as Piper Jaffray's Joshua Schimmer said one of his Top 15 potential "Surprise" Biopharma Events For 2015 includes bluebird bio curing sickle cell anemia.
Schimmer said 2015 is poised to be a big year for gene therapy, and success in alleviating the sickle cell phenotype with BLUE's approach would represent another landmark for the field. Heart failure and CHF are other gene therapy opportunities coming into focus in 2015 he said. "Other events in the gene therapy field in 2015 will likely include additional data from ophthalmology programs including AAVL (wet AMD) and AGTC (XLRS and achromatopsia)," he added.
Another interesting potential "Surprise" event in the sector, according to Schimmer, is that two large cap biotechs gets acquired. "The number of large-cap ( $10B) biotech companies which offer attractive long-term growth opportunities to meaningfully inflect EPS trajectories for large pharma companies continues to grow," the analyst commented. "The list now includes BIIB, CELG, BMRN, PCYC, VRTX, ALXN, REGN and INCY. All could be appealing M&A targets and fit needs of larger pharma partners. While many investors may agree that one would be a boon for an industry, two of these could lead to a broader sector revalidation."
Yet another potential "Surprise", is that MannKind and Sanofi Afrezza launch goes well.
Below is a list of Schimmer's Top 15 Potential "Surprise" Biopharma Events For 2015:
1. Gene therapy establishes proof of concept in hemophilia
2. Heart failure explodes on the biopharma scene with gene therapy success
3. Biopharma does even better in 2015 than it did in 2014
4. Failed trials get approved, starting with BMRN's drisapersen
5. BLUE cures sickle cell anemia
6. BIIB finishes the year with the best large-cap pipeline and freedom to operate on
7. SNY/MNKD Afrezza launch goes well
While MannKind did not book any revenue during the quarter, it received $150 million in an upfront payment from the closing of the Afrezza licensing agreement. Cash at quarter-end was $172.5 million, up from $41.2 million at June 30. Additionally, we model the first $25 million manufacturing and supply milestone in the fourth quarter, which could slip into the first quarter of 2015. Coupled with the $175 million line of credit with Sanofi, we project MannKind has sufficient cash. However, we expect MannKind to refinance its $100 million note due August 2015. Management reiterated that the U.S. commercial launch for Afrezza is on track for the first quarter of 2015, with sales and marketing plans to be finalized in the coming weeks. While details regarding the size of the salesforce were not disclosed, we were encouraged to learn that Afrezza will be the focus product for at least some of the salesforce, and, importantly, that the salesforce is experienced and will be "well-resourced." MannKind is presently manufacturing commercial supply, and management is confident that it will be able to supply Sanofi with inventory to launch. This is expected to trigger the first of three chemistry, manufacturing and controls (CMC) milestones totaling $75 million. Since two-thirds of research and development (R&D) expense (total R&D was $19.2 million in the third quarter) was allocated to commercial supply and manufacturing, we expect R&D expense to decline sharply in 2015 and thereafter as this expense will be booked as cost of goods sold following launch. At the Danbury, Conn., site, MannKind's three production lines (two awaiting validation) should support about $850 million in sales. According to MannKind, due to accounting rules, it cannot book either the $150 million upfront or $75 million worth of CMC-related milestone revenues until the Sanofi partnership becomes cash-flow positive.
Matt: machine order to cert is 6mos. 2 more lines are built out, wait for cert. $50M 2Q15
Ken: Why is Afrezza better than insulins currently sold by market leaders Novo Nordisk (NYSE:NVO) and Eli Lilly (NYSE:LLY)
Nate: To be sure, the advantage that gets talked about first – and usually with the most enthusiasm – is the fact that it is inhaled rather than injected, and while this will admittedly play a bigger role with newly diagnosed diabetics going forward, than it will with existing patients who are already used to injecting themselves several times a day, my own very small (and admittedly unscientific) survey suggests that a sizable portion of this patient population would also be more than happy to skip the injections, despite the fact that the needle sticks have become ‘tolerable’ as smaller and smaller needles have become available over the years.
In addition, a number of people I have spoken with have expressed excitement at the thought of being able to take their insulin during lunchtime meetings (or any other restaurant situation, for that matter) by simply taking a discrete puff on their inhaler, rather than leaving the table to give themselves an injection or playing the old “jab their leg under the table” game in order to spare others from watching the injection.
However, along with this “ease of use” feature, I believe an even more important piece of the puzzle is Afrezza’s pharmacokinetic (PK) profile, something we can talk about a little later in the interview.
Ken: If memory serves me correctly, there was another inhalable insulin on the market a few years ago, and it failed badly.
Nate: Well the last attempt at an inhalable insulin, Exubera, which was marketed by Pfizer (NYSE:PFE) did, in fact, go down as perhaps one of the greatest flops of all-time in pharmaceutical history. Pfizer pulled the plug on the product after it generated only $12 million in sales in its first nine months on the market! Needless to say, its resounding failure has been a cloud hanging over MannKind ever since.
Novel Diabetes Drugs Expanding
Austin, Texas—An unprecedented growth in treatment options for type 2 diabetes mellitus (DM) means more patients can achieve disease control, experts told attendees of the 2014 annual meeting of the American College of Clinical Pharmacy (ACCP).
Many patients have enthusiastically embraced the efficacy, convenience and added weight loss associated with sodium glucose co-transporter 2 (SGLT2) inhibitors and glucose-like peptide 1 receptor agonists (GLP-1 RAs), according to R. Keith Campbell, PharmD, CDE, the Distinguished Professor in Diabetes Care and Pharmacotherapy at Washington State University College of Pharmacy, in Pullman. “The more patients use these agents, the more they like them,” said Dr. Campbell, an expert who did not take part in the ACCP presentations.
New Oral Agents: SGLT2 Inhibitors
Because they can be used as monotherapy or as add-ons to other oral agents, SGLT2 inhibitors have proven versatile, said Matthew Strum, PharmD, a clinical assistant professor in the Department of Pharmacy Practice, University of Mississippi School of Pharmacy, in Oxford. He pointed to data showing that the recently approved SGLT2 inhibitor, empagliflozin (Jardiance; Boehringer Ingelheim), which joins canagliflozin (Invokana, Janssen) and dapagliflozin (Farxiga, Bristol-Myers Squibb), is most effective in combination with metformin.
The data are from an open-label, 78-week extension study that compared empagliflozin (10 or 25 mg) with sitagliptin (Januvia, Merck), metformin alone, or metformin combined with one of these two agents (Diabetes Care 2013;36:4015-4021).
The results showed that after 78 weeks of treatment, empagliflozin 25 mg in combination with metformin led to a mean 0.77% reduction in hemoglobin A1c (HbA1c) and a mean 32 mg/dL reduction in fasting plasma glucose. In contrast, sitagliptin with metformin was associated with a mean 0.13% reduction in HbA1c and a decrease of 16 mg/dL in fasting plasma glucose.
Weight Loss Advantage
The combination of empagliflozin 25 mg with metformin also led to reductions in systolic blood pressure (mean 3 mm Hg) and significant weight loss (mean 2.5 kg), Dr. Strum noted. “The weight reduction we’ve seen with both SGLT2 inhibitors and GLP-1 RAs gives them a significant advantage over other agents,” he said.
CANTATA-SU, a randomized, double-blind, Phase III trial, included 1,450 patients with type 2 DM, who received metformin with once-daily canagliflozin 100 or 300 mg, or with glimepiride, a long-acting sulfonylurea anti-diabetic drug (Lancet 2013;382:941-950). After 52 weeks of treatment, canagliflozin 300 mg with metformin led to a mean 4.0 kg reduction in weight, compared with a mean 0.7 kg weight increase in the glimepiride with metformin group, Dr. Strum said.
Subjects receiving the canagliflozin 300 mg/metformin combination also experienced a mean 0.93% reduction in HbA1c and a mean 27 mg/dL decrease in fasting plasma glucose. In contrast, subjects administered glimepiride with metformin experienced a mean 0.81% reduction in HbA1c and a mean 18 mg/dL decrease in fasting plasma glucose.
“One striking finding from a study of dapaglifozin as an add-on to pioglitazone was that dapagliflozin mitigated the weight increases that occur with pioglitazone monotherapy,” noted Dr. Strum, pointing to findings showing a mean 1.3-kg increase in weight in patients receiving 10 mg of dapaglifozin with at least 30 mg of pioglitazone daily, versus a mean 3 kg rise in weight in patients administered pioglitazone alone (Diabetes Care 2012;35:1473-1478). The greatest reductions in both HbA1c and fasting plasma glucose also occurred with a combination of the two agents, Dr. Strum said.
SGLT2 and Risk For Genitourinary Infections
A caveat to these positive findings is a risk for genital and urinary tract infections that accompanies all of the SGLT2 inhibitors, Dr. Strum noted. “The most common reason my patients have had to discontinue these agents is because they’ve developed a urinary tract infection, or in women, vulvovaginitis, or in uncircumcised men, balanitis [swelling of the head of the penis],” he said. The mechanism of action? “You are putting more glucose in the urine as a result of using these medications,” he explained. “A high-glucose environment is something that bacteria can thrive in; hence the increased risk for infection.”
GLP-1 Receptor Agonists
Two recent additions to the GLP-1 RA class of drugs, albiglutide (Tanzeum, GlaxoSmithKline) and exenatide synthetic (Bydureon, AstraZeneca), have the added convenience of once-weekly administration, said Krystal Edwards, PharmD, who is an associate professor in the Pharmacy Practice Department–Ambulatory Care Division at Texas Tech University Health Sciences Center’s School of Pharmacy, in Dallas/Fort Worth. “There are also strong efficacy data supporting their use,” said Dr. Edwards, who spoke at the same ACCP session.
Such evidence is documented in the randomized, open-label DURATION-3 trial, which compared exenatide synthetic 2 mg once weekly to glargine in 456 patients with type 2 DM who had not achieved adequate glycemic control with at least three months of treatment with oral glucose-lowering drugs at the maximum tolerated doses. Exenatide synthetic was found to effectively control hyperglycemia (Lancet Diabetes Endocrinol 2014;2:464-473). Some patients continued treatment with metformin or combined metformin and sulfonylurea during the trial.
After three years of treatment, the researchers found that HbA1c levels decreased by a mean 1.01% in patients receiving exenatide synthetic with or without the other oral agents, compared with a mean 0.81% reduction in those administered glargine, with or without the oral agents (P=0.03). Notably, rates of hypoglycemia were three times lower in patients treated with exenatide than in those given the other drug regimens (0.3 episodes per patient-year vs. 0.9 episodes with exenatide vs. glargine, respectively).
In contrast, safety data were less favorable: More exenatide synthetic recipients experienced gastrointestinal adverse events, including nausea (15% vs. 2% for exenatide synthetic vs. glargine, respectively), vomiting (6% vs. 3%) and diarrhea (14% vs. 7%).
“Although gastrointestinal adverse events with GLP-1 RAs are not uncommon, they are generally transient and do not require treatment discontinuation,” Dr. Edwards said.
Similar to the SGLT2 inhibitors, GLP-1 RAs are associated with weight loss, Dr. Edwards said, pointing to research demonstrating reductions of 1.5 kg to 4 kg after six to 18 months of type 2 DM treatment with exenatide or liraglutide (Diabetes Obes Metab 2014;16:9-21). In a trial of liraglutide in obese individuals, 64% of patients lost at least 5% of their body weight after a year of treatment with liraglutide 2.4 or 3 mg (Int J Obes [Lond] 2012;36:843-854).
FDA Acts on Positive Data
Results like these were impressive enough to prompt an FDA advisory panel to recommend approval of liraglutide for use as a treatment for obesity.
GLP-1 RAs may have other non-endocrine benefits, Dr. Edwards said. Investigators are analyzing potential related improvements in blood pressure, total cholesterol, low-density lipoprotein and triglycerides, Dr. Edwards noted (Diabetes Obes Metab 2014;129:2305-2312). “These effects are particularly useful in type 2 DM patients, since they frequently have these comorbidities,” she said.
According to Dr. Edwards, a barrier to wider clinical adoption of GLP-1 RAs is the accompanying risk for pancreatitis and pancreatic duct metaplasia. “Given reports of these complications, I would not administer these agents in patients with a history of pancreatitis, alcohol abuse or pancreatic cancer,” she said.
But there’s a caveat: The extent of the risk for pancreatitis and pancreatic cancer is disputed, and the FDA said in February 2014 that studies suggest there aren’t enough data showing a direct link (N Engl J Med 2014;370:794-797). However, the adverse effect is listed in the Warnings and Precautions section of the prescribing information for exenatide, liraglutide and albiglutide. Moreover, in a population-based, case-control study use of GLP-1 RAs within the past 30 days increased the risk for acute pancreatitis by 2.24 times, and use for between 30 days and two years increased the risk by 2.01 times (JAMA Intern Med; 2013;173:534-539).
Despite the risk for pancreatitis, the American Association of Clinical Endocrinologists recommends GLP-1 RAs as a possible first-line monotherapy for patients with type 2 DM who have a HbA1c less than 7.5%, but as part of combination therapy if HbA1c is equal to or greater than 7.5%, Dr. Edwards said (http://bit.ly/1ARfQwo). “Nevertheless, GLP-1 RAs may or may not be available on all formularies.”
That lack of access may be a loss for patients, she suggested. “More and more data are coming out showing GLP-1 RAs have the potential to preserve §-cells” (Diabetes Obes Metab 2013;15:485-502).
Afrezza Approval Makes Splash
Although SGLT2 inhibitors and GLP-1 RAs are important additions to clinicians’ armamentarium, “the biggest news in diabetes treatment is the approval of the pulmonary insulin, Afrezza [MannKind],” stressed Dr. Campbell. “It begins working within minutes, peaks within 15 minutes, and is associated with few instances of hypoglycemia,” he said.
The failed launch of Pfizer’s Exubera, another inhaled insulin that was approved by the FDA in 2006 and quickly removed from the market due to low sales, may not bode well for Afrezza. But in Dr. Campbell’s view, differences between the two agents make it more likely that Afrezza will be widely adopted into clinical practice.
“Afrezza has greater pulmonary absorption and requires less patient education,” he said. “Patients needed half an hour of training to understand how to use Exubera. Afrezza, in contrast, requires one minute of training.”
Dr. Strum reported serving on the speaker’s bureau for Janssen and as a consultant for Insulet, Medtronic and Tandem as a certified insulin pump trainer. Drs. Edwards and Campbell reported no relevant financial conflicts of interest.
Ultra Long-Acting Basal Insulins on the Horizon
Austin, Texas—Clinicians can expect the ultra long-acting basal insulin degludec (Tresiba, Novo Nordisk) to be approved in 2015, Robin Koffarnus, PharmD, told attendees of the 2014 annual meeting of the American College of Clinical Pharmacy. She said the agent can be injected at intervals up to 40 hours apart, while conferring the same reliable efficacy of shorter-acting insulin formulations.
“In patients who do not achieve glycemic control with oral medications, insulin will likely be effective,” said Dr. Koffarnus, an assistant professor of pharmacy practice at Texas Tech University Health Sciences Center School of Pharmacy, Dallas/Fort Worth campus.
In the 26-week, open-label, BEGIN FLEX trial, insulin degludec administered at intervals of up to 40 hours was as effective as the shorter-acting insulin glargine (Lantus, Sanofi) in reducing hemoglobin A1c (HbA1c) level, with better patient compliance and fewer incidents of hypoglycemia (Diabetes Care 2013;36:858-864).
Novo Nordisk filed for FDA approval of its product in 2013, but after the FDA’s own analyses showed an increased risk for cardiovascular events, the company was asked to conduct clinical trials focusing solely on major cardiovascular events (http://goo.gl/csDrHN).
R. Keith Campbell, PharmD, CDE, the Distinguished Professor in Diabetes Care and Pharmacotherapy at Washington State University College of Pharmacy in Pullman, commented that the drug should have been approved the first time around. “I was truly shocked that the FDA required more data on Tresiba,” said Dr. Campbell, referring to the European trade name of insulin degludec, approved there in early 2013. “Myself and other insulin experts agreed the many studies of Tresiba showed it to be an excellent, safe and effective basal insulin, and there did not appear to be any reason to conduct further studies.”
According to Dr. Koffarnus, clinicians could see two other ultra long-acting basal insulin drugs approved in the next couple of years. The first, insulin glargine U300 (Sanofi), was found to be as effective as its shorter-acting formulation (Lantus, Sanofi) in reducing HbA1c and fasting plasma glucose levels, while proving superior in reducing incidents of hypoglycemia (see Riddle, MC, et. al. 73rd Scientific Sessions of the American Diabetes Association; abstract 43-LB).
Furthermore, in a 12-week, randomized, open-label Phase II trial, the second drug, insulin peglispro (Eli Lilly), also proved as effective as insulin glargine in improving these outcomes, but was associated with less intraday plasma glucose variability, fewer instances of nocturnal hypoglycemia and notable weight loss (Diabetes Care 2012;35:2140-2147).
Although findings on the three agents are encouraging, Dr. Koffarnus believed they should be taken with a grain of salt. “Real-world use and outcomes can be very different than what we see in clinical trials,” she said. “We’ll see how they do in the clinic.”
Actually, we are ahead of schedule. Hakan said we'd have 3 lines cert'ed in first half 2015. $25 M bonus per line. The 3rd one has been built out at the same time as the 2nd one. Its cert is in progress. St expected $25M bonus 1Q15. Thus, $50 M beat expectations. Expect positive St reaction today.
Despite getting $150 million upfront as part of its deal with Sanofi, MannKind can't book the revenue because accounting rules say that the company has to amortize it over the life of the profitable partnership. Until Afrezza launches and MannKind can make a reasonable guess as to how long profits will last, it can't book the revenue.
But GAAP accounting isn't particularly useful for evaluating a biotech. If it was, there would be no way investors would let MannKind rack up a nearly $2.5 billion loss over the past 13 years.
What is important is having enough of a nest egg to get to cash flow-positive, and despite not being able to book the $150 million payment, MannKind still has that cash from Sanofi in the bank. It also got $40 million as part of its deal with Deerfield and another $17.3 million from the exercising of warrants and stock options in the third quarter.
All told, MannKind ended the third quarter with $172.5 million. Add in another $70 million in potential borrowing from Deerfield and $30 million line of credit from CEO Al Mann, and MannKind is sitting on a nice nest egg.
And it gets even better. Part of the deal with Sanofi includes manufacturing milestones broken into three parts worth $25 million each. It appears the first one of those milestones might be paid soon.
And once the launch happens, much of the manufacturing costs, which are currently captured in research and development expenses, will be reimbursed by the partnership, so MannKind won't have to use incur those expenses. And since it's already purchased insulin to manufacture the devices, the transfer of the expenses off its expense report will result in a cash gain for the company.
The partnership won't be profitable for a while, but that won't affect MannKind's nest egg -- at least not for a while. Sanofi will cover the first $175 million of MannKind's 35% portion of the partnership's loss in the form of a line of credit.
So what's MannKind going to do with the cash? It's working on a new manufacturing design that could lower cost and make higher dosage strength of insulin. There's also the potential to use its inhalation technology, Technosphere, to deliver other drugs into blood stream via the lungs thereby avoiding injections, reducing gastrointestinal side effects, and/or increasing the onset of the drug. MannKind is remaining mum on exactly which drugs those might be, but it did specifically mention pain medications where rapid onset would be a welcome relief.
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.
Matt said that they wouldn't announce anything for Technosphere until after the Afrezza launch, then he later said that they plan to announce in February after the Board meeting. I'm thinking it's a January launch now.