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.

picture 1

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.

picture 1

Release Details

Positive Afrezza® Clinical Data from STAT Study Published in Diabetes Technology & Therapeutics

09/13/18
PDF Version
Study data show Afrezza provides greater improvement in postprandial glucose control than insulin aspart

WESTLAKE VILLAGE, Calif., Sept. 13, 2018 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq:MNKD) announced today that "Improved Postprandial Glucose with Inhaled Technosphere® Insulin Compared to Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The STAT Study" has been published online in Diabetes Technology & Therapeutics.  

The STAT study is the first randomized, controlled study to assess diabetes control using continuous glucose monitoring and Afrezza® in individuals with type 1 diabetes. The dual primary endpoints were:

  • 24-hour glucose time-in-range (TIR)
  • Postprandial glucose excursions (PPGE), defined as the peak increase in glucose in the 1 to 4 hour post-meal period

This trial, supported by funding from MannKind Corporation, was a pilot study led by investigators at the Barbara Davis Center for Diabetes.  

Compared to standard of care for mealtime therapy, the per-protocol use of Afrezza (i.e. supplemental doses 1 and/or 2 hours post-meal), on average demonstrated:

  • Significantly increased glucose TIR by approximately 2 hours per day
  • Significantly reduced time in hyperglycemia > 180 mg/dL
  • Significantly lower PPGE 1 to 4 hours post-meal
  • Significant reductions in glucose as early as 60 minutes following Afrezza dose
  • Less hypoglycemia (as measured by time spent less than 60 mg/dL); notably, the average Afrezza-treated individual spent approximately 3 minutes per day with blood glucose values less than 50 mg/dL compared to approximately 12 minutes per day for aspart-treated individuals              

This is the first of a number of planned randomized trials, intended to evaluate the potential benefits of Afrezza (Technosphere Insulin) compared to the standard of care for mealtime plus basal insulin.

“I am very pleased to have helped develop the design of this novel trial (STAT) at the Barbara Davis Center for Diabetes, performed as a collaborative multi-center clinical trial with several other investigators around the country,” stated Halis Kaan Akturk, M.D., Assistant Professor of Medicine and Pediatrics, Barbara Davis Center for Diabetes, University of Colorado Denver and the principal investigator of the STAT study. “With the peer review publication of these data in Diabetes Technology & Therapeutics, we feel that our data supporting the unique time-action profile of Technosphere Insulin (Afrezza®) is helping us to better understand the potential advantages of a truly rapid-acting insulin delivery system for improving control of mealtime glucose. Specifically, individuals with type 1 diabetes, treated with Technosphere Insulin, demonstrated lower blood glucose as early as one hour after meals and, based on our analysis, supplemental dosing with Technosphere Insulin further improved the glucose control measured after meals. These data are the first to demonstrate that individuals living with type 1 diabetes may achieve significant improvement in postprandial glucose with Technosphere Insulin as a mealtime insulin, compared to standard of care, rapid-acting insulin analogs.”

“These new data significantly advance our understanding of the potential clinical benefits of Afrezza therapy for those living with type 1 diabetes,” stated David Kendall, M.D., Chief Medical Officer of MannKind Corporation. “We believe one of the key limitations to optimal glucose control and achieving better outcomes for people living with diabetes is their ability to control mealtime glucose levels. These data generated to date further support the view that Afrezza has the potential to be the treatment of choice for those individuals with diabetes who require alternatives that further improve mealtime glucose control. The completion of this proof-of-concept trial and peer-reviewed publication allows for broad sharing of these data with diabetes healthcare professionals.” 

The published research can be found online at https://www.liebertpub.com/doi/10.1089/dia.2018.0200

About Afrezza®
Available by prescription, Afrezza® (insulin human) Inhalation Powder is a rapid-acting inhaled insulin indicated to improve glycemic control in adult patients with diabetes mellitus. Afrezza consists of a dry powder formulation of human insulin delivered from a small and portable inhaler. Administered at the beginning of a meal, Afrezza dissolves rapidly upon inhalation to the lung and passes quickly into the bloodstream (in less than one minute). This rapid absorption allows Afrezza to begin reducing blood sugar levels within about 12 minutes of administration. Afrezza is available in 4-unit, 8-unit and 12-unit single-dose cartridges of insulin powder that can be used, as prescribed by a health care professional, in combination with other diabetes medications to achieve target blood sugar levels. For Afrezza doses exceeding 12 units, patients may use a combination of existing cartridge strengths. For more information on Afrezza, please visit www.afrezza.com.

About MannKind Corporation
MannKind Corporation (NASDAQ:MNKD) focuses on the development and commercialization of inhaled therapeutic products for patients with diseases such as diabetes and pulmonary arterial hypertension. MannKind is currently commercializing Afrezza® (insulin human) Inhalation Powder, the Company's first FDA-approved product and the only inhaled rapid-acting mealtime insulin in the United States, where it is available by prescription from pharmacies nationwide. MannKind is headquartered in Westlake Village, California, and has a state-of-the art manufacturing facility in Danbury, Connecticut. The Company also employs field sales and medical representatives across the U.S. For further information, visit www.mannkindcorp.com.

Forward-Looking Statements
This press release contains forward-looking statements that involve risks and uncertainties. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind'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 various risks and uncertainties detailed in MannKind's filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2017. 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.

Company Contact:
Rose Alinaya
SVP, Investor Relations
818-661-5000
ir@mannkindcorp.com

MannkindLogoStackedPreferd.jpg

Source: MannKind