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Technosphere®

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.

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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.”

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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

AFREZZA Demonstrates Non-Inferiority Compared to Standard Therapy in Controlling Blood Sugar Levels in Type 1 Diabetes Patients

06/10/10
AFREZZA Demonstrates Non-Inferiority Compared to Standard Therapy in Controlling Blood Sugar Levels in Type 1 Diabetes Patients

VALENCIA, Calif., Jun 10, 2010 (BUSINESS WIRE) --MannKind Corporation (NASDAQ: MNKD) today announced that results of a new 16-week trial show that the investigational ultra rapid acting mealtime insulin, AFREZZA™ (insulin human [rDNA origin]) Inhalation Powder, combined with basal insulin, is clearly non-inferior to standard therapy insulin lispro, a rapid acting insulin, also combined with basal insulin, in reducing HbA1c levels in subjects with inadequately controlled Type 1 diabetes. In addition, patients treated with AFREZZA had statistically significant lower rates of hypoglycemia, post-prandial glucose (PPG) levels when measured at 30, 60, 90 and 120 minutes, and fasting blood glucose (FBG) levels when compared to subcutaneously injected insulin lispro.

"Effectively controlling blood sugar levels and managing hypoglycemic events go hand in hand as key to successfully treating patients with Type 1 diabetes," said Satish K. Garg, M.D., Professor, Departments of Pediatrics and Medicine, University of Colorado School of Medicine; Head, Young Adult Diabetes Clinic, Barbara Davis Center for Childhood Diabetes, and lead study investigator. "Our findings demonstrate that AFREZZA may offer a significant advance from current mealtime insulin delivery methods, as it is comparable to the standard of care in glycemic control and provides the additional benefit of lower hypoglycemia rates."

Diabetes, which affects 26.8 million people in the U.S., is characterized by the body's inability to properly regulate levels of blood glucose, or blood sugar. Insulin, a hormone produced by the pancreas, normally regulates the body's glucose levels, but in people with diabetes insufficient levels of insulin are produced or the body fails to respond adequately to the insulin it produces. Historically, mealtime insulin therapy regimens have had a number of limitations, including the risk of severe hypoglycemia, the likelihood of weight gain, inadequate post-meal glucose control, the need for complex titration of insulin doses in connection with meals and the need for injections. Additionally, these therapies have not mimicked the natural time-action profile of insulin normally seen in healthy individuals and presented challenges in maintaining compliance.

AFREZZATM is a novel, ultra rapid acting mealtime insulin therapy being developed by MannKind Corporation for the treatment of adult patients with Type 1 and Type 2 diabetes for the control of hyperglycemia. It is a drug-device combination product, consisting of AFREZZA Inhalation Powder pre-metered into single use dose cartridges and the small, discreet and easy- to-use AFREZZA Inhaler. Administered at the start of a meal, AFREZZA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, mimicking the release of meal-time insulin observed in healthy individuals. To date, the AFREZZA clinical program has involved more than 50 different studies and over 5,000 adult patients with both Type 1 and Type 2 diabetes.

Study Design and Key Findings

Patients with inadequately controlled Type 1 diabetes (7% < HbA1c less-than or equal to 9%) were randomized to treatment with either AFREZZA plus insulin glargine (n=65) or insulin lispro plus insulin glargine (n=65) over 16 weeks. The primary objective was to demonstrate that the efficacy of AFREZZA in combination with insulin glargine was non-inferior to the efficacy of lispro in combination with insulin glargine . Secondary endpoints included the percentage of patients achieving HbA1c target goals of less-than or equal to 7.0% and less-than or equal to 6.5%, PPG excursions following the ingestion of a standardized meal (meal challenge), and the rates of hypoglycemia.

In the intent-to-treat population, AFREZZA lowered HbA1c by -0.10% (mean change from baseline HbA1c) as compared to -0.03% in the lispro group. The difference of 0.07% between the two groups fell well within the non-inferiority margin of 0.4% (95% CI [-0.31, 0.17]). Similar results were also observed in the intent-to-treat with last observation carried forward population (-0.04%; 95% CI [-0.25, 0.18]). In addition, a significantly higher percentage of patients in the AFREZZA group (9.6%) reached an HbA1c goal of less than 6.5% compared to the lispro group (3.5%, p = 0.0277).

Even with matching levels of glargine, patients treated with AFREZZA experienced significantly greater decreases in FBG levels (mean change from baseline 41.53 mg/dl in the AFREZZA group versus 9.16 mg/dl in the lispro group, p = 0.0107). Patients treated with AFREZZA also experienced significantly lower PPG levels at 30, 60, 90 and 120 minutes (mean PPG levels at 30 minutes AFREZZA 130 mg/dl versus lispro 195.09 mg/dl; 60 minutes: AFREZZA 136 mg/dl versus lispro 214.49 mg/dl; 90 minutes: AFREZZA 163.94 mg/dl versus lispro 228.45 mg/dl; 120 minutes: AFREZZA 199.53 mg/dl versus lispro 241.39 mg/dl). In addition, patients treated with AFREZZA had significantly lower rates of total and mild/moderate hypoglycemia (6.2 versus 8.2 events per subject month [p=0.0345] and 6.0 versus 8.0 events per subject month [p=0.0269], respectively).

About MannKind Corporation

MannKind Corporation (Nasdaq: MNKD) focuses on the discovery, development and commercialization of therapeutic products for patients with diseases such as diabetes and cancer. Its diabetes pipeline includes AFREZZA™ and MKC253. MKC253 is currently in phase 1 clinical trials. In March 2009, MannKind submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) requesting approval of AFREZZA for the treatment of adults with Type 1 or Type 2 diabetes for the control of hyperglycemia. In March 2010, MannKind received a Complete Response to this NDA from the FDA requesting additional information. An End-of-Review meeting was held in June 2010 and MannKind is currently preparing its resubmission of the AFREZZA NDA. Other products in MannKind's pipeline include the cancer immunotherapy products MKC1106-PP and MKC1106-MT, which are currently in phase 1 clinical trials. 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.

SOURCE: MannKind Corporation 

Investors:
MannKind Corporation
Matthew Pfeffer
Chief Financial Officer
mpfeffer@mannkindcorp.com
(661) 775-5300
or
Media:
MCS Healthcare Public Relations
Laura de Zutter
laurad@mcspr.com
(908) 234-9900