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 Presents Positive Original Analyses of Afrezza® Clinical Data at  American Diabetes Association (ADA) 80th Scientific Sessions

06/15/20
PDF Version

WESTLAKE VILLAGE, Calif., June 15, 2020 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD) announced that new data from clinical studies of Afrezza® (insulin human) Inhalation Powder was presented at the American Diabetes Association’s 80th Scientific Sessions, June 12-16, 2020.

The data presented includes:

  • A comprehensive post hoc analysis of four unique studies assessing the safe and effective dosing of Afrezza in patients with type 1 diabetes1 (Poster 1023)
  • An analysis demonstrating treatment with Afrezza is associated with weight loss in patients with type 2 diabetes, compared to weight gain with injected mealtime insulin2 (Poster 1024)
  • An evaluation of a comprehensive two year safety study showing that significant changes in FEV1 (as a measure of pulmonary function) during treatment with Afrezza are both uncommon and generally transient in nature3 (Oral Abstract 235)

”We are pleased to present these clinical studies detailing the safe and effective use of Afrezza at this year’s virtual ADA Scientific Sessions,” stated David Kendall, MD, Chief Medical Officer MannKind. “These studies provide further support of the effectiveness and clinical safety of Afrezza therapy and offer important insights on effective dosing of Afrezza, the favorable effect of Afrezza on body weight, and the improvement in clinical outcomes possible when converting patients to Afrezza therapy.” 

Highlights of the presentations are described below. See the appendix for presentation details.

Poster 1023: Dose Titration and Clinical Effects of Inhaled Technosphere® Insulin Compared with Mealtime Subcutaneous (SC) Analog Insulin Therapy in Type 1 Diabetes (T1D)

  • Ultra rapid-acting Afrezza can be safely and effectively dosed at 1.5 to 2.0 times that of injected mealtime insulin
  • This dosing ratio appears to be consistent across a range of A1C responses
  • Afrezza’s ultra rapid-acting profile may supersede the perceived precision of injected mealtime insulin dosing and provides patients the ability to flexibly dose based on glycemic response

Poster 1024: Technosphere® Insulin Added to Basal Insulin Is Associated with Less Weight Gain than Basal Insulin plus Insulin Aspart or Insulin Analog (aspart) 70/30 Mixture in Type 2 DM

  • Patients with type 2 diabetes treated with Afrezza showed modest weight loss while those treated with insulin aspart or insulin aspart mix resulted in weight gain 
  • The weight difference estimate between Afrezza and insulin aspart was 1.83 pounds
  • The weight difference estimate between Afrezza and biaspart insulin was 3.17 pounds
  • The effect on body weight was independent of the magnitude of improvement in glucose control

Oral Abstract 235: Incidence of Significant Changes in Pulmonary Function during A 2-year Study with Inhaled Technosphere® Insulin

  • Prior clinical studies have shown a modest (~40 ml) difference in mean change in FEV1 over two years when comparing treatment with Afrezza to other diabetes therapies
  • The majority (88%) of individuals treated with Afrezza had no significant change in FEV1 measured at any time
  • Overall, 98% of patients on Afrezza (vs. 99% of usual care) had either no significant change (≥15%) or were observed to have only a transient change in FEV1 over the two years of study

About Afrezza®

Available by prescription, Afrezza® (insulin human) Inhalation Powder is an ultra 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 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 about 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 ultra 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. For a discussion of these and other factors, please refer to MannKind’s annual report on Form 10-K for the year ended December 31, 2019 as well as MannKind’s other filings with the SEC. 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.

MannKind Contact:
Investor Relations
818-661-5000
ir@mannkindcorp.com

Appendix – Presentation Details
(1) Poster Presentation: Dose Titration and Clinical Effects of Inhaled Technosphere® Insulin Compared with Mealtime Subcutaneous (SC) Analog Insulin Therapy in Type 1 Diabetes (T1D)
Presenter: David M. Kendall, M.D.
Poster No. 1023-P
Date/Time: Saturday, June 13; 10 AM CT

(2) Poster Presentation: Technosphere® Insulin Added to Basal Insulin Is Associated with Less Weight Gain than Basal Insulin plus Insulin Aspart or Insulin Analog (aspart) 70/30 Mixture in Type 2 DM
Presenter: David M. Kendall, M.D.
Poster No: 1024-P
Date/Time: Saturday, June 13; 10 AM CT

(3) Oral Presentation: Incidence of Significant Changes in Pulmonary Function during A 2-year Study with Inhaled Technosphere® Insulin
Presenter: David M. Kendall, M.D.
Poster No: 235-OR
Date/Time: Sunday, June 14; 5:30 PM CT


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Source: MannKind