What exactly is the Technosphere® Platform?

One of the largest organs in your body are the lungs. Picture the size of a full tennis court and that is roughly the surface area of both lungs in a typical adult. Running through those lungs are airways whose total length measures 1,500 miles – that’s the distance between Chicago and Las Vegas, New York to Albuquerque, and Los Angeles to Nashville.

Simply put, the lungs create a wonderful platform for effective drug delivery. MannKind’s Technosphere technology recognizes this and provides the distinct advantage of rapid, deep lung drug delivery. The effect is similar to intravenous delivery (I.V.; within a vein) and has the added benefit of bypassing the liver which can be especially helpful in reducing systemic side effects.

Examining it closer, it helps to look at inhalation, air flow travel, and the exhale. When you breathe in, air is drawn into the lung and flows down curving, narrowing airways that end in the air sacs or alveoli. When air is exhaled, the flow is reversed. Between the end of an inhalation and the start of exhalation, the air in the lung is stationary. To reach the deep lung, inhaled particles must be carried by the air stream and have enough momentum to continue through the stationary air to collide with the lung surface.

Particles that can reach the lung have aerodynamic diameters between 0.5 µm and 5-6 µm (1 µm is 1 micro-meter or about 0.00004 inches). Particles that are larger than 6 µm will leave the air stream and hit the back of your mouth and throat; smaller than 0.5 µm wouldn’t have the ability to reach the lungs and would simply get exhaled.

“The average Technosphere particle is about 2-2.5 µm which is in the middle of the respirable range,” explains Marshall Grant, PhD, MSc, Executive Director, Clinical Pharmacology & Research for MannKind Corporation. “The particle size distribution is a major reason Technosphere powders are highly efficient in delivering drug to the lungs than other dry powder inhalers (DPIs).”

The Technosphere particles in FDA-approved Afrezza® (insulin human) Inhalation Powder and Tyvaso DPI™ (treprostinil) Inhalation Powder are manufactured by different processes and possess different characteristics. But both are made up of small crystals of FDKP (fumaryl diketopiperazine), MannKind’s proprietary molecule. FDKP provides high solubility and fast dissolution at physiologic pH – and more importantly – can crystallize and form particles in the range appropriate for optimum delivery to the lungs.

When Technosphere powder reaches the lung surface, the FDKP and drug dissolve. The FDKP is then rapidly cleared from the lung into systemic circulation. The FDKP is not metabolized, but rather excreted primarily in the urine. Another value of Technosphere powders has been their versatility – they are compatible with a wide range of doses with different types of drugs.

MannKind’s Technosphere powders are delivered into the lung’s airstream via an inhalation device or DPI (dry powder inhaler). The breath-powered inhalers (Dreamboat® being the most common version) provide excellent delivery efficiency and are proven to deliver up to 70% of the dry-powder dose deep into the lungs. Our DPI are designed to be simple, easy to use and discreet. For patients, imagine having a drug in the convenient form of an inhaler that fits in the palm of your hand. This approach allows patients to not only take control of their health but do it while going about their day and enjoying life more humann.

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NTM Lung Disease on the Rise

“I cough every morning upon waking, so I don’t feel rested.” “Imagine not being able to breathe.” “Anxiety ruins everything about you – it’s not a normal life.” “You just exist from day to day and week to week.” These are a sampling of comments about the most bothersome symptoms from living with Nontuberculous Mycobacteria (NTM) shared in a study from NTM Info & Research, Inc. The statements are unfortunately typical and those with NTM often have unpredictable day-to-day health functioning and reduced quality of life.

NTM lung disease is a serious infection that is caused by bacteria that are common in the environment and can cause lung damage. The reality is that we are all exposed to these bacteria in our day-to-day lives – more than 120 species of mycobacteria have been identified. These common bacteria exist in water and soil particles that are in the air, wet places like hot tubs, steamy bathrooms, dishwashers, and even the dewy ground we walk on at the park. But not everyone is at risk of getting NTM lung disease just because they are exposed.

Those predisposed often have underlying conditions such as asthma, COPD, and bronchiectasis, which makes them prone to NTM infection. NTM is not considered to be contagious. Women over the age of 65 make up the majority of those impacted, with a predominance in those of Caucasian and Asian descent.

A rare disease, NTM can often be difficult to diagnose. Many will experience coughing, fatigue, weight loss and shortness of breath – all of which are common with other lung disease symptoms and other conditions like tuberculosis. With NTM, symptoms often worsen, and that is a marker not to be ignored.

It is estimated that some 86,000 individuals are living with NTM lung diseases, and it is on the rise growing 8% each year. Coastal regions including Gulf States have higher rates of infection accounting for 70% of annual NTM cases.

While no cure is available, treatments to manage NTM are available. Treatment for NTM involves antibiotic and multidrug regimens with duration lasting from months to years with tolerability and adverse reactions to treatment which often leads to a lack of adherence to therapy.

There is a valuable need to develop medicines that are well tolerated and effective that lends to consistent patient use and alleviates symptoms of NTM lung disease. MannKind continues to progress MNKD-101 (Clofazimine) for the treatment of NTM.

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Release Details

MannKind to Manufacture 12 Unit Cartridge Strength of AFREZZA(R) Following FDA Approval

04/27/15
PDF Version

VALENCIA, Calif., April 27, 2015 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq:MNKD) today announced that it will begin to manufacture a 12 unit cartridge strength of AFREZZA (insulin human) Inhalation Powder to improve glycemic control in adult patients with diabetes. The 12 unit cartridge was approved by the U.S. Food and Drug Administration on April 17, 2015 and is expected to be launched by Sanofi in the second half of 2015.

The new dosage strength complements the existing 4 unit and 8 unit cartridges and will provide patients with another option to receive their prescribed dose.

About Afrezza®

Afrezza® (insulin human) Inhalation Powder is used to control high blood sugar in adults with type 1 and type 2 diabetes. The drug-device combination product consists of a dry formulation of human insulin delivered in a specially designed inhaler. Administered at the beginning of a meal, Afrezza® delivers insulin into the body through the lungs with peak insulin levels achieved within 12 to 15 minutes. Afrezza® is available in 4-unit and 8-unit single-use cartridges that can be combined to meet the prescribed dose. In addition, the U.S. Food and Drug Administration (FDA) recently approved a 12-unit cartridge strength of insulin powder for Afrezza®. The disposable inhaler can be used to take the cartridges for up to 15 days and does not require cleaning or maintenance. 

Sanofi and MannKind have entered into a worldwide exclusive licensing agreement to develop and commercialize Afrezza®. Under the collaboration agreement, Sanofi is responsible for global commercial, regulatory and development activities.

INDICATIONS AND USAGE FOR AFREZZA® (insulin human) Inhalation Powder

Prescription Afrezza® is a man-made rapid acting inhaled insulin breathed through your lungs and is used to control high blood sugar in adults with type 1 and type 2 diabetes.  

Limitations of Use:

  • Do not use Afrezza® in place of long-acting insulin; Afrezza® must be used with a long-acting insulin in patients with type 1 diabetes.
  • Do not use Afrezza® to treat diabetic ketoacidosis.
  • It is not known if Afrezza® is safe and effective for use in people who smoke. Afrezza® is not for use in patients who smoke or who have recently stopped smoking (less than 6 months).
  • It is not known if Afrezza® is safe and effective in children under 18 years of age.

Important Safety Information for Afrezza®

WARNING: RISK OF SUDDEN LUNG PROBLEMS (BRONCHOSPASMS) IN
PATIENTS
WITH LONG-TERM (CHRONIC) LUNG DISEASE

  • Sudden lung problems (acute bronchospasm) have been seen in patients with asthma and COPD (chronic obstructive pulmonary disease) using Afrezza®.

  • Afrezza® is not to be used in patients with long-term lung disease such as asthma or COPD.

  • Before initiating Afrezza®, your doctor will perform a detailed medical history, physical examination, and a breathing test (called spirometry) to identify potential lung problems.

Do not use Afrezza® if you have problems with your lungs, such as asthma or COPD (chronic obstructive pulmonary disease). Do not use Afrezza® during a low blood sugar reaction (hypoglycemia). If you are allergic to regular human insulin or to any of the ingredients in Afrezza®, do not use Afrezza® as this may cause a significant and severe allergic reaction.

Before using Afrezza®, it is important to tell your doctor about all your medical conditions, including if you have a history of lung problems, if you smoke or have recently quit smoking, if you are pregnant or plan to become pregnant, or if you are breast feeding or planning to breast-feed. Tell your doctor about all other medicines and supplements you take.

Your doctor will take a medical history, and do a physical exam and a breathing test (called spirometry) to determine if you have lung problems. Patients with lung problems should not use Afrezza®. If your doctor finds you have lung problems, use of Afrezza® may cause a severe asthma-like breathing problem. Afrezza® can reduce lung function, so your doctor will also want to test your breathing 6 months after starting Afrezza®, and then each year after that, even if you have no lung symptoms. More frequent testing should be done if you have symptoms such as wheezing or coughing. 

You must test your blood sugar levels while using insulin, such as Afrezza®. Do not make any changes to your dose or type of insulin without talking to your healthcare provider. Any change of insulin should be made carefully and only under your doctor's care. 

There are certain serious side-effects that are associated with the use of Afrezza®.

Severe allergic reaction (including whole body reaction) is one of the serious side effects. Get medical help right away if you have any signs or symptoms of a severe allergic reaction,including a rash over your whole body, trouble breathing, a fast heartbeat, or sweating. 

Low blood sugar (hypoglycemia) is one of the most common side effects of insulin, including Afrezza®, which can be serious and life-threatening. Common symptoms of hypoglycemia are dizziness or light-headedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood change, or hunger. It may cause harm to your heart or brain. It is important for you to understand how to manage the use of Afrezza®, and to understand how to lessen the risk of hypoglycemia events.

Lung cancer occurred in more people who were taking Afrezza® compared to other diabetes medications. There were too few cases to know if lung cancer was related to Afrezza®. Tell your doctor if you currently have lung cancer, have had it in the past, or if you have an increased risk of developing lung cancer.

Heart failure can occur if you are taking insulin together with certain medicines called TZDs (thiazolidinediones), even if you have never had heart failure or other heart problems. If you already have heart failure it may get worse while you take TZDs with Afrezza®. Tell your doctor if you have any new or worsening symptoms of heart failure including shortness of breath, swelling of your ankles or feet or sudden weight gain. Your treatment with Afrezza and TZDs may need to be changed or stopped if you have new or worsening heart failure.

Get emergency help if you have trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, or confusion.

While using Afrezza do not drive or operate heavy machinery until you know how Afrezza affects you. You should not drink alcohol or use other medicines that contain alcohol and you should not smoke.

The most common side effects of Afrezza® include low blood sugar (hypoglycemia), cough, sore throat, headache, diarrhea, tiredness, and nausea.

Please see full Prescribing Information, including Boxed WARNING, at www.afrezza.com.

Afrezza® is a registered trademark of MannKind Corporation.

About MannKind Corporation

MannKind Corporation (Nasdaq:MNKD) focuses on the discovery and development of therapeutic products for patients with diseases such as diabetes. MannKind maintains a website at http://www.mannkindcorp.com to which MannKind regularly posts copies of its press releases as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to e-mail alerts that are sent automatically when MannKind issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the website.

Forward-Looking Statements

This press release contains forward-looking statements that involve risks and uncertainties. Words such as "believes", "anticipates", "plans", "expects", "intend", "will", "goal", "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon the Company's current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, MannKind's dependency on Sanofi for commercialization of Afrezza, manufacturing effectiveness and other risks detailed in MannKind's filings with the Securities and Exchange Commission, including the Annual Report on Form 10-K for the year ended December 31, 2014 and periodic reports on Form 10-Q and Form 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.

CONTACT: Company Contact:

         Matthew J. Pfeffer

         Chief Financial Officer

         661-775-5300

         mpfeffer@mannkindcorp.com