Timothy M. Anderson - Sanford C. Bernstein & Co. LLC
I just wanted to clarify your earlier comments on the recent reorganization. Did you say that it would not necessarily lead to any cost savings? That's my first question.
Second question is on M&A. The company obviously has a long history of doing deals. Nothing substantial has happened since Genzyme a few years ago. I'm wondering how the company is viewing the landscape at the moment, along the lines of current valuations of potential targets. And is M&A potentially on hold for the company, given the recent change in leadership and also the reorganization and the need to reassess the direction of the company?
And then my last question is on biosimilar Lantus. You note on one of your slides that it has launched in two Eastern European markets. I'm wondering if you can tell us what the effective price is of the biosimilar relative to Lantus in those two markets.
Olivier Brandicourt - Chief Executive Officer
All right, Tim. Thank you for your questions. So, again, I'd like to come back to the aim of achieving this transformation first. So, I mentioned focus, simplification; it will increase speed of decision-making. During the first quarter, I insisted that we need to have single point of accountability to improve governance and that's part of the equation, overall decreasing complexity across the organization.
And because of what I mentioned about specialization, I think that should lead to engaging more deeply our customers in those different lines of businesses. And one point is to allocate resources more effectively and efficiently. So, if we do that and if we do the last one, then we should logically see some savings. That should lead to some saving that could be reinvested in the business and R&D. So, that's the answer.
The second is M&A. M&A, yeah, it's part of the tools we may use for the right opportunity. I think that's what we are saying for a little while. We have not been engaged in M&A in the last two or three years. But before that, as you underlined, Sanofi was involved in midsize like Genzyme or bolt-on acquisitions such as Merial and Chattem. And this is definitely part of what we can continue to do or start again to do. Our balance sheet is pretty strong and our debt level is low. And that would be my answer.
On the biosimilar Lantus, yes, we do have some information and Peter Guenter will give you that.
Peter Guenter - Executive VP-Global Commercial Operations
Yeah. Hi, Tim. So, as we speak, we have three countries actually in Europe. We have Czech Republic, Slovakia and Estonia where the product had been introduced and the price differential compared to the Lantus price varies between 15% and 20%, one five and 20%. What is also already known is that we expect Lilly to launch in the UK, which would be their first significant market, obviously. We expect them to launch in September and we know that the price differential there will be 15%, that is one five percent to be precise.
Six Things to Know Before Starting Afrezza
Some of you may have heard that I’ve been having issues with Afrezza, the new inhalable insulin from MannKind/Sanofi that’s such a hot commodity among investors.
I’m disappointed that it doesn’t seem to be working as well for me now as it did at the outset (I’ve been using it since mid-March), but I am in direct contact with the product team to troubleshoot, in the hopes that I can return to the amazing results I saw back in Spring.
Meanwhile, purely in the interest of helping fellow patients who may wish to try Afrezza, here are six things you may want to know before you get started:
1) Adjusting Quantity – Be aware that you will need MORE Afrezza than any other short-acting insulin. The “units” of Afrezza are by no means a one-to-one relationship to the unit measures we PWDs (people with diabetes) are used to. You may also find, like I have, that while a 4-unit dose of Afrezza packs a punch in the early days of use, as time goes on you need to increase your dosage. So think about ordering the mixed pack of Afrezza, that includes 4 and 8-unit cartridges. Otherwise, if you need higher doses, you may end up having to inhale 3 or 4 times or more per meal, which is highly inconvenient. Sanofi’s Senior Medical Director Diabetes and U.S. Medical Lead for Afrezza Anders Boss tells me the 12-unit option that’s now FDA approved may be available as early as September.
2) Inhalation Technique – Boss also reminds us that it’s important to hold the device level before inhaling, and then tilt it just a little bit down towards your chin while dosing. Do not point it upwards at all. Also be sure to take a long, deep inhalation, rather than sucking it into your mouth like you might when smoking a pipe. (And by all means don’t hold the inhaler upside-down, like I did in my initial photo mishap; although NOTE that was simply a photo opp gone bad. I NEVER used the inhaler that way, and am pretty sure it’s actually impossible to do so. Correct inhaler positioning shown below.) See also this Afrezza training video for best practices on inhalation technique. Afrezza inhaler
Also: Boss says refrigerated Afrezza should be allowed to rest at room temperature for about 10 minutes before you use it, because a too-cold cartridge can create condensation, causing the powder to clump and get stuck in the top of your mouth. (There’s one problem you never imagined having with insulin, ay?!)
3) Colds and Cough – When I caught a cold and got very phlegmy earlier this summer, I found it very difficult to dose Afrezza without coughing it out mid-inhalation. The effects of this actually lasted for several weeks after the rest of my cold symptoms were gone. I could actually see the white powder coming out my mouth or nose as I struggled to keep my cough in check while dosing.
Interestingly, Boss says that having a common cold should not interfere with Afrezza’s effectiveness. He says in studies, they’ve started patients who had a cold and compared the results to those of healthy patients, without incident. All I can tell you from personal experience as a type 1 pumper is that if you do have a cold, a little bolus boosting from your pump may be in order – especially since being sick increases your overall insulin needs. And to reduce the “cough effect,” be sure to exhale hard each time before attempting to inhale Afrezza.
4) Leftover Powder – I was also very worried about seeing some residual white powder left in the cartridge after most doses: was all the insulin really getting into me?
But Boss reassures us that a little leftover powder in a used cartridge should not cause concern. The manufacturers Afrezza cartridgedon’t expect 100% absorption, which is also the case with injected insulin, he says. “It’s OK if about 8% still seems to be in the cartridge afterwards. That’s calculated in. You lose some in the mouth, some in the cartridge. It’s such a fine powder that most of it absorbs in the lungs.” OK. Wow.
5) Two-Unit Option & Kids – Those who do continue to need small amounts of Afrezza will be happy to hear that Sanofi is actively “looking at a 2-unit option, with correction doses in mind and for kids.”
In fact, they are in the process of setting up pediatric trials now, Boss says. The first study will focus on pharmacogenetics (genetic drug response) to be sure that children will absorb inhaled insulin the same way, and whether they can handle 4-unit doses.
6) ePatients Beware – If you plan to blog, or in particular, Tweet about your experiences with Afrezza, beware investor trolls! They are mostly obvious with brand new Twitter accounts showing only an “egghead” profile pic, and a timeline that talks nothing but #Afrezza. Some are more subtle. But all are pretty ruthless in their attempts to control the message in the interest of influencing MannKind stock prices to their own advantage. I guarantee that unless you are saying 100% glowingly positive things about Afrezza all the time, you will be hounded and patronized. I encourage you to BLOCK anyone who is obviously in that camp, possibly using a new tool called Blocktogether (thx @ScottLeibrand for that tip!)
Afrezza in the Real World - DiabetesMine
We’d love to hear from any PWDs out there using Afrezza in the trenches of day-to-day diabetes. What have you learned that might be share-worthy? Please don’t be afraid to speak up.
Sales of MannKind's inhaled insulin continue slow start - LA Times
MannKind Corp.’s inhaled insulin drug Afrezza continued its slow launch in the second quarter of the year.
Sanofi, the French pharmaceutical company that’s selling Afrezza in a partnership agreement with MannKind, said it sold just $2.2 million of the drug in the quarter that ended June 30. That means that in its first five months, sales have reached just $3.3 million – a disappointing result considering some analysts expect sales to reach $1 billion a year.
MannKind’s stock was down 1 cent, or 0.2%, to $4.43 at 12:15 p.m. Pacific time. It initially fell 10%, but rebounded later in the trading session.
Matthew Pfeffer, MannKind’s chief financial officer, said he expects sales to pick up as Sanofi launches a direct-to-consumer marketing campaign. This month, Sanofi placed a three-page advertisement in Time magazine, seeking to increase consumer awareness of the new drug. It has also expanded sales staff assigned to market the drug, Pfeffer said.
“Advertising and new Internet-based marketing efforts did not begin until this quarter, so their effects have not yet been seen,” Pfeffer said in an email.
The Food and Drug Administration approval of Afrezza in June 2014, following more than a decade of research, testing and regulatory setbacks.
MannKind’s founder, 89-year-old Alfred Mann, said he expects Afrezza to become one of the top-selling drugs in U.S. history. He said its benefit goes far beyond the convenience of inhaling instead of injecting it; Afrezza is extremely fast-acting and clears the body quickly. Instead of having to plan insulin injections long before meals, users can take a quick puff of Afrezza immediately before eating.
The FDA, however, required that all patients pass a lung-function test before they can use the drug. It also ordered MannKind to include a warning that the drug should not be used by smokers or people with lung disease.
Cost is another consideration. Sanofi’s wholesale price for 20 units a day of Afrezza is $9.29, compared with $5.23 for its injected insulin, Apidra. Sanofi is offering coupons on its website to help patients cover co-pays.
To this point, the biggest marketing push has come from Afrezza users, who have used social media sites such as Twitter and Reddit to spread the word. Many users of the drug have said they are extremely happy with its effectiveness.
Analysts at Goldman Sachs are pessimistic about Afrezza’s future, rating Mannkind's stock a sell and saying in a recent report that the number of prescriptions is “far too low to reach profitability near-term.” The investment bank has lowered its sales estimate for the drug twice this year.
EBM: Can you update us on the Diabetes performance this quarter? How is the launch of Toujeo® progressing?
Olivier Brandicourt: Diabetes sales declined 3.8% during the Q2, consistent with the previous quarter and in-line with our expectations for the full year.
Diabetes sales in the U.S. decreased 14% year-over-year to just over 1.1 billion euros, mainly reflecting the continued pricing impact on Lantus®. Diabetes sales in the U.S. accounted for 57% of worldwide Diabetes sales or about 12.1% of Group sales. Importantly, sales outside the U.S. represented 43% of total Diabetes sales and increased 11.2% to 854 million euros, which offset a substantial portion of the negative pricing impact in the U.S. market.
Toujeo®, our next-generation basal insulin, was launched in the U.S. market at the end of March. Total sales of the product were about #$%$13 million in the second quarter and #$%$20 million in the first half. Importantly, we have already achieved significant market access. As of early August, 73% of lives covered by commercial plans have unrestricted access to Toujeo®, including 45% of lives with preferred Tier 2 access. In Medicare Part D, 91% of lives are covered with unrestricted access to Toujeo®. This is a very encouraging start and we are successfully defending our position in the total U.S. basal market.
Following EU approval in April, Toujeo® was launched in Germany, the Netherlands and some Nordic countries. Toujeo® was also recently approved in Japan, Canada and Australia.
SECOND QUARTER RESULTS 2015
July 30, 2015
Second Quarter Results 2015 will be presented by the management during a live audio webcast. The presentation will be followed by a Q&A session.
In order to facilitate analysts’ forecasts on Q2 results 2015, Sanofi would like to highlight the following items:
Pre-quarterly Results Communication
7:30 am CET / 1:30 am EST: Press Release
2:30 pm CET / 8:30 am EST: Live audiocast of the conference call with the financial community
Call in numbers
France: +33 (0) 1 70 77 09 47
UK: +44 (0) 203 0432 439
US: +1 866 907 5925
France: +33 (0) 1 72 00 15 01
UK: +44 (0) 203 367 9460
US: +1 877 64 230 18
Conference code: 295043#
AFREZZA GUY (@Afrezzaguy) tweeted at 11:19am - 18 Jul 15:
@MrHaigs @Cigna Cigna covered Afrezza from the very beginning they recognized a game changer and I never had any issues.
AFREZZA GUY (@Afrezzaguy) tweeted at 11:22am - 18 Jul 15:
@MrHaigs @Cigna I went through their home delivery and received a 3 month supply of #afrezza for $80 which Sanofi refunded thru card program
Cigna (@Cigna) tweeted at 1:35am - 18 Jul 15:
@Afrezzaguy Hi, thank you for the positive feedback. If there's anything I can help with, please email me at LetUsHelpU@CignaDOTcom.Thank You
AFREZZA GUY (@Afrezzaguy) tweeted at 1:52am - 18 Jul 15:
@Cigna thanks and I will-thank you for recognizing the power of Afrezza it is a life changer. A1c averaging 5.4 over last ten weeks
MaredinCapital (@Marcelozinn) tweeted at 8:04am - 17 Jul 15:
@Marcelozinn: Q. to #afrezza users: from time you called ur Dr, got apt, had spirometry test, how long was entire process to get Rx?
Julie (@julie007_y) tweeted at 7:27pm - 17 Jul 15:
@Marcelozinn it took about a month since insurance req prior Auth..I've been on afrezza since April. Check out @afrezzauser or
AFREZZA GUY (@Afrezzaguy) tweeted at 1:26am - 18 Jul 15:
@Marcelozinn I have @Cigna and had no issues with coverage. Sanofi rep had lung test dr all set up and ready to go after Endo appt
AFREZZA GUY (@Afrezzaguy) tweeted at 1:28am - 18 Jul 15:
@Marcelozinn most difficult part was getting Rx doses from Endo to match with Boxes Cigna had. Lung test was 20 mins in and out.
Studies have demonstrated that in-creased adherence to a treatment regi-men can reduce A1C levels,10 and many other studies have shown that A1C reductions prevent complications. A 1% reduction in A1C is associated with a 14% reduction in the risk of heart attack and a 40% reduction in the risk of eye, kidney, and nerve disease.11 (Logic says that better adherence would also slash healthcare costs, but the findings from research on that topic are mixed.10)
A number of experiments have tested different strategies for improving ad-herence to existing treatment regimens. Many have failed, but many others have produced significant gains, at least over the study period, with simple ap-proaches such as asking pharmacists to provide patients a little extra information.12 While some researchers continue to study ideas for motivating patients, others work to improve treatments.
Some people, for example, respond poorly to existing medications, so even if patients used existing options perfectly, there would still be a need for more effec-tive options. The biggest need, however, appears to be medications that promote compliance by making treatment regimens less arduous and more tolerable. Only real-world use will show if Toujeo and Afrezza meet that second need, but there are several reasons for hope.
For one, the reduction in nocturnal hy-poglycemia associated with using Toujeo rather than Lantus is reasonably large. A meta-analysis of 3 of the drug’s phase 3 trials found a 31% reduction in such reactions among 2476 patients (risk ratio, 0.69; 95% CI, 0.57-0.84; P = .0002).13
While the biggest original selling point for Lantus may have been the relatively low rate of nocturnal hypoglycemia, low blood sugar remains a serious problem. Hypoglycemia is the primary cause of roughly 282,000 emergency department visits each year,9 and many patients fear it enough to risk high blood sugar by taking less insulin than their doctors prescribe.14
Toujeo and Afrezza: New and Improved Insulins, Limited by FDA Labeling Constraints
Existing treatments are effective enough to control diabetes in most patients, but drug makers spend huge sums to keep developing new products and improving old ones.
Indeed, Sanofi just rolled out 2 novel versions of the very oldest diabetes treatment, an insulin glargine formulation called Toujeo and an inhalable form of human insulin called Afrezza.
Sanofi officials say both products will benefit large numbers of insulin users with both type 1 and type 2 diabetes mel-litus (T1DM, T2DM). Outsiders express a wide range of opinions.
Trial data indicate that Toujeo controls glycated hemoglobin (A1C) levels about as well as Lantus, an insulin glargine formulation approved in the year 2000 that has just lost patent protection after years of blockbuster sales. Toujeo lasts longer than Lantus, however.1 It also provides the body a steadier stream of insulin1 and is associated with a significantly lower risk of nocturnal hypoglycemia.1
Afrezza performed similarly in a phase 3 trial. It roughly matched an existing competitor, insulin aspart (Novolog), in A1C reduction, and slightly outperformed it in several secondary ways. Afrezza use was associated with less hypoglycemia, lower fasting blood glucose, and slight weight loss rather than slight weight gain. It also reached peak levels very quickly, in just 12 to 14 minutes on average.2
That said, Afrezza’s medical importance will likely hinge on something that no trial can measure: how the change from injection to inhalation affects patient behavior. If the delivery method inspires patients to medicate themselves more consistently, Afrezza could produce huge health benefits. If patients use Afrezza like they use insulin aspart (a fast-acting insulin analogue), the new product could prove to be an expensive convenience.
Financial analysts mostly predict solid but unspectacular sales for both drugs, in part because federal regulations for-bid Sanofi from touting the comparative advantages of either drug. (The FDA did not allow language about less hypoglycemia in the label it approved, and therefore Sanofi cannot mention it in language it uses to promote the drug.)
Consensus estimates reported by Bloomberg predict annual Toujeo sales will reach about $1.3 billion by 20203 far below the $7.1 billion that Lantus generated in 2014. As for Afrezza, annual projections range from a paltry $182 million up to $2 billion, with the median in the $600 million range. The treatment’s unexpectedly poor performance during its first month on the market led Goldman Sachs to cut its annual sales projections by $1 billion.4
In other respects, however, both medications have gotten a good reception.
“The response to Afrezza on social media has been tremendous,” Rachele Berria, MD, PhD, who heads the Diabetes Medical Unit for Sanofi US, told Evidence-Based Diabetes Management in an interview. “Healthcare providers don’t seem to anticipate that patients will see much of a need to move away from injections, but actual patients see this as a valuable feature.”
Berria says the company will study real-life Afrezza use to see if patient enthusiasm translates into patient compli-ance, and that it will follow real-world Toujeo users to measure the practical effect of its longer, steadier flow of medication. “The goal in treating diabetes is to avoid peaks and valleys in both insulin and sugar, and Toujeo does that to a degree that once seemed impossible,” she said. “There’s no insulin spike when each new injection gets absorbed, and there’s no loss of efficacy in the final few hours. It’s a big stride forward from Lantus.”
Physicians have been using insulin to treat diabetes since 1922, when Frederick Banting and Charles Best injected the hormone into a diabetic teenager at a hospital in Toronto. Eli Lilly began producing it commercially within the year, and diabetes was transformed, virtually overnight, from a speedy death sen-tence to a chronic condition.5
Intermediate acting Neutral Prot-amine Hagedorn (NPH) insulin arrived about a quarter century later, in 1950. Long-acting insulin, on the other hand, didn’t reach patients until 2000, when Lantus went on sale in the United States and Europe.
The new drug reduced A1C levels about as much as NPH insulin, but trials demonstrated that it produced a greater reduction in fasting plasma glucose and fasting blood glucose as well as a far lower risk of nocturnal hypoglycemia.6
The other big advantage of Lantus was the convenience of longer action. Patients who had spent years toting around basal insulin and setting alarms for midday injections suddenly had nothing to carry and nothing to remember except a single injection before bed. By then, of course, insulin was not the only effective treatment for T2DM. The FDA had approved metformin in 1994, and its huge success spurred drug companies to develop the other oral treatments that now crowd the market.
Many of these treatments are quite effective, especially when used in combination. Indeed, if used properly, their excellent disease control could greatly reduce diabetic complications and the need for new drugs.
Yet pharmaceutical companies continue developing treatments like Toujeo and Afrezza because a huge percentage of diabetics fail to control their condition with current options. A recent study that examined records from more than 43,000 patients found that less than 55% of all Americans who have been diagnosed with diabetes, and prescribed medication to control blood sugar, actually man-age to keep their A1C level under 7%.7
The main cause of this problem seems to be patient behavior. Studies have found that patient adherence to oral treatment protocols can range from more than 90% down to just over 50%. Strict adherence to guidelines concerning injectable medications and proper diet tends to be lower, while strict ad-herence to guidelines concerning mod-erate, regular exercise and blood sugar checks is downright rare.8 The chance that any patient will adhere perfectly to a complex regimen is low, and studies of people with all types of chronic disease have typically found that only about half of them will make a serious effort to manage their condition.8
The consequences of this behavior are dire.Diabetes is the nation’s seventh-lead-ing cause of death. It increases the risk of stroke (by 50%), heart attack (by 80%), and death from cardiovascular disease (by 70%). It is also the leading cause of kidney failure and non-traumatic lower limb amputation. The American Diabetes Association estimates that the di-rect medical cost of treating diabetes reached $176 billion in 2012, and indi-rect costs such as lost productivity add-ed another $69 billion to the tally.
David Kliff: @nickcullinane never said #afrezza doesn't work as a therapy this isn't about whether it works or not
7:32am - 17 Jul 15
$MNKD picture from Time Aug 3rd addition. Is $SNY committed to #afrezza ? You tell me. By KC. pic.twitterDOTcom/qy92aeVyrq
July/ August issue of Diabetic Living has a Long article on Afrezza. Next month an Ad? We will see. pic.twitterDOTcom/pD87hJWTbz
Laureen (@Reen910) tweeted at 3:42pm - 23 Jul 15:
Called Caremark to get preauth for Afrezza and nice rep was interested. Aft I explained she's asking her doc #Afrezza #afrezzaadvocateS
Check from MMIT apps, Afrezza, NewYork, Commercials
Hundreds of Cos such as AFLAC, Unions in NY covers Afrezza via Express Scripts PBM Tier 3, No PA (Prior Authorization), ST (Step Therapy) restrictions. Matt said Exubera initial sales was better than Afrezza due to No PA required and earlier DTC Ads.
A No cancer result could remove or mitigate the worst part of Afrezza label. The Hypo risk will also be removed after Superiority trials complete in Jan 2016. Good label and improved mkt access would give Sny Medical Affairs more ammo to persuade Docs at dinner seminars.
Anthem Blue Cross GenRx, CA, Preferred, Approved
BC CA RightPlan PPO 40 Generic, Preferred, Approved
Reuters) - Anthem Inc said on Friday it would buy Cigna Corp in a deal valued at $54.2 billion, creating the largest U.S. health insurer by membership.
The deal — the biggest ever in the health insurance industry — comes three weeks after Aetna Inc agreed to buy Humana Inc for $37 billion and is part of an industry-wide consolidation following the roll-out of President Barack Obama's healthcare law.
Antitrust authorities are expected to aggressively scrutinize how the combinations will affect competition for Medicare and individual and commercial insurance.
By most measures, U.S. insurance markets are extremely concentrated. That means companies could have trouble selling assets if forced to do so by antitrust regulators.
Anthem said it expects the deal to close in the second half of 2016, indicating a long regulatory road ahead.
Anthem and Cigna are two of just four major insurers that administer self-insured plans for major companies. The other two are UnitedHealth Group Inc and Aetna.
UnitedHealth is currently the biggest U.S. health insurer by membership, while Anthem and Cigna rank No. 2 and No. 4.
"When you go from four to three national players, that creates a significant issue," said Matthew Cantor of law firm Constantine Cannon LLP.
Anthem said it was confident it would get all necessary regulatory and other approvals.
The combined company would have about 53 million members.
UnitedHealth had 45.86 million members as of June 30.
Growing concerns about market concentration came into sharp focus earlier this year when regulatory concerns scuttled Comcast Corp's $45 billion bid for Time Warner Cable Inc.
Anthem said it will pay $103.40 in cash and 0.5152 of its shares for every Cigna share.
The deal is valued at $183.36 per share based on Anthem's Thursday close of $155.21.
Cigna shares were up 0.2 percent at $154.68 in premarket trading, while Anthem shares were up 0.5 percent at $156.06.
The equity portion of the offer is valued at $49.11 billion, according to Reuters calculations based on 261.2 million Cigna shares outstanding as of March 31.
Anthem said the offer is valued at $188 per share, based on its unaffected share price as of May 28 before reports that the two companies were in talks.
The company has said the acquisition will help it reduce costs and allow it to negotiate lower prices with doctors and hospitals.
The combined company will be led by Anthem Chief Executive Joseph Swedish. Cigna Chief Executive David Cordani will be president and chief operating officer.
Anthem's lead financial adviser is UBS Investment Bank. Credit Suisse also served as financial adviser, and White & Case LLP as legal adviser.
Morgan Stanley is Cigna's financial adviser and Cravath, Swaine & Moore LLP its legal adviser.
I didn't realize that one of the biggest impediment to Afrezza adoption is fear of lung cancer until I visited my PCP for a severe cold. I asked him if he prescribed Afrezza. He said he used to prescribe Exubera for needle phobics. He had degree in PharmD, MD, and Eastern medicine Dr as well. He wouldn't prescribe unless needle phobic PWD demand it as lung cancer is a big risk. I argued Al said Mnkd has X-ray'ed 5-yr non-smoking users. There was no sign of lung cancer. My PCP replied 5 yrs is not long enough. It may take 10 yrs or more to develop lung cancer from foreign substance. I didn't have any answer for that. He said many of his peers heard about Afrezza efficacy. However, they wouldn't prescribe it due to long term cancer concerns unless needle phobic PWDs demand it or a 20-yr FDA trial conclusively determines that lung cancer is not an issue. This couples with market access really kill this stock. That's why this trial is so monumentally important.
This data will be very interesting but still inaccurate as just an Afrezza study because the patients will have probably about 2 years of Exubera use before the 6 years of Afrezza. Anyways, still a study of nearly 8 years of inhaling insulin. This would still be worth something to look at how this "long term" use affected these patients.