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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

Studies Show AFRESA(R) Controls Post-Meal Sugar Levels With Less Weight Gain and Hypoglycemia Risk for Diabetes Patients

06/06/09
Studies Show AFRESA(R) Controls Post-Meal Sugar Levels With Less Weight Gain and Hypoglycemia Risk for Diabetes Patients

NEW ORLEANS, June 6 /PRNewswire-FirstCall/ -- The findings of two 52-week studies show that the investigational ultra rapid acting insulin AFRESA® (insulin human [rDNA origin]) Inhalation Powder combined with basal insulin is comparable to standard of care therapies in controlling post-meal blood sugar levels, and also results in significantly less weight gain and risk of hypoglycemia for adult patients with diabetes. The data were presented today at the American Diabetes Association's 69th Scientific Sessions.

"The unique pharmacokinetic profile of AFRESA allows this product to rapidly achieve peak insulin levels," said John Gerich, M.D., Program Director, Clinical Research Center, Department of Medicine, University of Rochester School of Medicine and Dentistry. "These results indicate that AFRESA may be a promising new therapy for patients with type 1 and type 2 diabetes, as it controls post meal-time glucose levels with the added benefits of less weight gain and lower risk of hypoglycemia."

AFRESA is a novel, ultra rapid acting mealtime insulin therapy with an action profile that mimics meal-related early insulin release. Based on an extensive phase 3 clinical program, a New Drug Application (NDA) has been accepted by the U.S. Food and Drug Administration (FDA) requesting approval to market AFRESA Inhalation Powder and the AFRESA Inhaler for use in adult patients with type 1 and type 2 diabetes mellitus for the treatment of hyperglycemia. AFRESA is conveniently administered by oral inhalation.

Type 2 Study Design and Key Findings

Patients with type 2 diabetes who were inadequately controlled (A1C 7.0% and < /=11.0%) despite insulin with/ without oral anti-hyperglycemic therapy were randomized to a 52-week course of either AFRESA (TI) and bedtime glargine insulin (G) (n=334) or premixed biaspart 70/30 insulin BID (BPA 70/30) twice-a-day (n=343). The primary endpoint was mean change from baseline to week 52 in A1C. Secondary objectives were proportion of subjects reaching specific A1C levels and treatment differences in postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and weight.

A1C was reduced by -0.66% and -0.72% in the TI+G and BPA 70/30 groups, respectively, and the proportion of subjects achieving A1C <7.0% were comparable between treatments (22% vs 27%). One-hour PPG change from baseline after a meal challenge was significantly lower in the TI+G group (37 vs. 54 mg/dL; p<0.0001). TI+G produced significantly less weight gain (0.9 vs. 2.5 kg; p=0.0002) and significantly less mild/moderate (48 percent vs. 69 percent, p<0.001) and severe (4 percent vs. 10 percent, p=0.0066) hypoglycemia compared to the BPA 70/30 group. Mean changes from baseline to week 52 in pulmonary function tests were similar in the two groups.

Type 1 Study Design and Key Findings

In the second study, patients with type 1 diabetes (A1C 7.0% and < /=11.0%) were randomized to a 52-week trial comparing AFRESA (n=301) with insulin aspart, a rapid acting analog (RAA) (n=288), both given at meals with insulin glargine, a long-acting analog (LAA). Pre-specified efficacy endpoints included change in A1C, 1-hour PPG, 2-hour PPG and FPG following a standard meal challenge, and body weight. Adverse events were monitored to compare safety profiles.

Reductions in A1C were comparable in both treatment groups with no significant differences in LAA doses in either group. FPG levels (-35.5 +/- 3.3 vs. -20.6 +/- 3.2, p=0.0012) and 1-hour PPG (20.9 +/- 4.79 vs. 40.5 +/- 4.56, CI=0.0022) values were significantly lower with AFRESA than with RAA. Patients in the AFRESA group lost weight (-0.5 +/- 0.3), while patients in the RAA group gained weight (+1.4 +/- 0.3), with the difference being statistically significant (p<0.0001). Finally, the AFRESA group had a statistically significant reduction in the incidence of mild/moderate (odds ratio [OR] 0.474, confidence interval [CI] 0.271, 0.831; p=0.0091) and total hypoglycemia (OR 0.488; CI 0.278, 0.856; p=0.0124).

About Diabetes

Diabetes, which affects 23.6 million people in the U.S., or 8 percent of the population, 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 (type 1 diabetes) or the body fails to respond adequately to the insulin it produces (type 2 diabetes). Current mealtime insulin therapy regimens have 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, current therapies do not mimic the natural time-action profile of insulin normally seen in healthy individuals and present challenges in maintaining compliance.

About AFRESA®

AFRESA® is a novel, ultra rapid acting mealtime insulin therapy being studied for use in adult patients with type 1 and type 2 diabetes mellitus for the treatment of hyperglycemia. It is a drug-device combination product, consisting of AFRESA Inhalation Powder pre-metered into single use dose cartridges and the light, discreet and easy to use AFRESA Inhaler. Administered at the start of a meal, AFRESA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, effectively mimicking the release of meal-time insulin observed in healthy individuals. The AFRESA phase 2/3 clinical program included over 4,500 adult patients.

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 pipeline includes AFRESA, which has completed phase 3 clinical trials, and MKC253, which is currently in phase 1 clinical trials. Both of these investigational products are being evaluated for their safety and efficacy in the treatment of 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 SEC or posts certain other information to the website.

Poster #466-P; Session PO01, June 6, 11:30 A.M. - 1:30 P.M.

Poster #479-P; Session PO02, June 7, 12:00 P.M. - 2:00 P.M.

CONTACT: Alanna Jamieson, MCS Healthcare Public Relations, alannaj@mcspr.com, (908) 234-9900

SOURCE MannKind Corporation

CONTACT:
Alanna Jamieson,
MCS Healthcare Public Relations,
+1-908-234-9900,
alannaj@mcspr.com,
for MannKind Corporation

Web Site: http://www.mannkindcorp.com