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

MannKind Announces Six-Month Results From Phase 3 INHALE-1 Pediatric Diabetes Trial Utilizing Inhaled Insulin (Afrezza®)

12/16/24
PDF Version
  • Company plans to meet with FDA regarding potential sNDA submission in 1H 2025
  • Call planned today at 8:30 a.m. (ET) to discuss company’s diabetes program progression

DANBURY, Conn. and WESTLAKE VILLAGE, Calif., Dec. 16, 2024 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products and devices for patients with endocrine and orphan lung diseases, today announced six-month results from its Phase 3 INHALE-1 study of Afrezza (insulin human) Inhalation Powder in children and adolescents (aged 4-17 years of age). MannKind expects to submit a request for a supplemental new drug application (sNDA) meeting with the U.S. Food and Drug Administration (FDA) in 1H 2025 to discuss the data and filing timeline.

The INHALE-1 study is a 26-week, open-label clinical trial that randomized 230 subjects to one of two groups: Afrezza or multiple daily injections (MDI) of rapid acting insulin analog (RAA) in combination with basal insulin. The primary endpoint was a non-inferior change in HbA1c levels after 26 weeks. A 26-week extension phase in which all remaining MDI patients switched to Afrezza is still ongoing.

Results were as follows:

Graph 1
 

* mITT analysis excludes one outlier from the primary ITT endpoint who failed to adhere to the study protocol

An analysis of the full intent-to-treat population (ITT) found that the between-group difference in mean HbA1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), largely driven by the variability of a single patient who did not adhere to the study protocol. A modified ITT (mITT) analysis, which excluded this subject, did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing the non-inferiority of Afrezza to MDI, which was the primary endpoint of the study.

Over 26 weeks of treatment, no difference in lung function parameters were seen between the treatment groups. The Afrezza-treated patients had a mean FEV1 of 2.901 liters (99.6% of predicted) at baseline and 2.934 liters (96.6% of predicted) at 26 weeks. MDI-treated patients had corresponding mean FEV1 values of 2.948 liters (102.3% of predicted) and 2.957 liters (98% of predicted), respectively. Additional safety findings, including for hypoglycemia, did not show any significant concerns or differences between the treatment groups.

“The overall efficacy and safety outcomes seen in the first 26 weeks are encouraging. This represents a monumental step in our more than 25-year history of pioneering the development of inhaled insulin and working to bring this new treatment option to children and adolescents over the past seven years,” said Dr. Kevin Kaiserman, Senior Vice President, Therapeutic Area Head, Endocrine Diseases for MannKind Corporation.

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said Dr. Roy W. Beck, founder of the Jaeb Center for Health Research who provided oversight for INHALE-1. “The six-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes.”

Conference Call
MannKind will host a live audio webcast beginning at 8:30 a.m. Eastern Time on Monday, December 16, 2024, to share results and discuss the company’s diabetes program progression. Participating in the conference call from MannKind will be Chief Executive Officer Michael Castagna, PharmD and Dr. Kaiserman. The webcast will be accessible via a link on MannKind’s website at https://investors.mannkindcorp.com/events-and-presentations. A replay will also be available in the same location within 24 hours following the call and be accessible for approximately 90 days.

About Afrezza
Afrezza (insulin human) Inhalation Powder is a rapid-acting inhaled human insulin indicated to improve glycemic control in adults with diabetes mellitus.

Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis or in patients that smoke or have recently stopped smoking.

Important Safety Information

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE

  • Acute bronchospasm has been observed in Afrezza-treated patients with asthma and COPD
  • Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
  • Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
     

Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.

Please see additional Important Safety Information, Full Prescribing Information, including BOXED WARNING, available on Afrezza.com/safety.

About MannKind
MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of innovative inhaled therapeutic products and devices to address serious unmet medical needs for those living with endocrine and orphan lung diseases.

We are committed to using our formulation capabilities and device engineering prowess to lessen the burden of diseases such as diabetes, nontuberculous mycobacterial (NTM) lung disease, pulmonary fibrosis, and pulmonary hypertension. Our signature technologies – dry-powder formulations and inhalation devices – offer rapid and convenient delivery of medicines to the deep lung where they can exert an effect locally or enter the systemic circulation, depending on the target indication.

With a passionate team of Mannitarians collaborating nationwide, we are on a mission to give people control of their health and the freedom to live life.

Please visit mannkindcorp.com to learn more, and follow us on LinkedIn, Facebook, X or Instagram.

Forward-Looking Statements
This press release contains forward-looking statements about a planned meeting with the FDA, a potential sNDA submission and the potential expanded use of Afrezza that involves 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, which include, without limitation, the risk that issues that develop in the review by the FDA may subject us to unanticipated delays or prevent us from obtaining the expanded indication as well as other risks detailed in MannKind’s filings with the Securities and Exchange Commission, including under the “Risk Factors” heading of its Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent periodic reports on Form 10-Q and current reports on 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.

AFREZZA and MANNKIND are registered trademarks of MannKind Corporation.

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/12f4dac8-7936-41b3-a2ad-7eef85fe3712


For MannKind:
Media Relations
Christie Iacangelo, (818) 292-3500
Email: media@mnkd.com
Investor Relations
Ana Kapor, (818) 661-5000
Email: ir@mnkd.com

Primary Logo

 
Graph 1

 

Graph 1

Source: MannKind