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 and Vertice to Co-Promote Thyquidity™ (levothyroxine sodium) Oral Solution

12/17/20
PDF Version

WESTLAKE VILLAGE, Calif. and NEW PROVIDENCE, N.J., Dec. 17, 2020 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD) and Vertice Pharma today announced that they have entered into a co-promotion agreement for Thyquidity™ (levothyroxine sodium) oral solution through MannKind’s specialty sales force. THYQUIDITY is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. THYQUIDITY is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients or hypothyroidism during the recovery phase of subacute thyroiditis.

Under the terms of the agreement, MannKind’s sales force will promote Thyquidity to adult endocrinologists, pediatric endocrinologists and other US healthcare providers who treat hypothyroidism. Vertice will make a specified quarterly payment to MannKind to defray the costs of the additional promotional activity and will pay MannKind royalties on gross profit resulting from all sales of Thyquidity.

“We are excited to co-promote Thyquidity with Vertice Pharma,” said Michael Castagna, Chief Executive Officer of MannKind. “This arrangement allows us to strengthen our relationships with our current customers, expand into pediatric endocrinology and leverage the talent and capabilities of our sales force and reimbursement support systems.”

“The team at Vertice Pharma is thrilled to be joining forces with MannKind to help launch our product to patients and healthcare providers,” said Scott Meyers, Chief Executive Officer of Vertice Pharma. “I look forward to working with MannKind’s commercial team to get ready for the launch of Thyquidity in 1Q 2021.”

Hypothyroidism, also called underactive thyroid disease, is a common disorder in which the thyroid gland does not produce enough thyroid hormone. The prevalence of hypothyroidism is 4.6% in the US population.1 Symptoms include fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin.2 Most patients require lifelong therapy to treat their hypothyroidism.3

INDICATION

Hypothyroidism
THYQUIDITY (levothyroxine sodium) oral solution is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

Pituitary Thyrotropin (Thyroid Stimulating Hormone, TSH) Suppression
THYQUIDITY is indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

Limitations of Use

THYQUIDITY is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients, as there are no clinical benefits and over-treatment with THYQUIDITY may induce hyperthyroidism.

THYQUIDITY is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

Important Safety Information

WARNING: NOT FOR TREATMENT OF OBESITY OR WEIGHT LOSS
Thyroid hormones, including THYQUIDITY, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

  • THYQUIDITY is contraindicated in patients with uncorrected adrenal insufficiency.
  • In the elderly and in patients with cardiovascular disease, THYQUIDITY should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease. If cardiac symptoms develop or worsen, the THYQUIDITY dose should be reduced or withheld for one week and restarted at a lower dose.
  • Patients with coronary artery disease who are receiving THYQUIDITY should be monitored closely during surgical procedures for cardiac arrhythmias. Monitor patients during concomitant administration of THYQUIDITY and sympathomimetic agents for signs and symptoms of coronary insufficiency.
  • Use of oral thyroid hormone is not recommended in myxedema coma. Products formulated for IV administration should be used to treat myxedema coma.
  • Patients with adrenal insufficiency should be treated with replacement glucocorticoids prior to initiating treatment with THYQUIDITY. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated.
  • THYQUIDITY has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is necessary to avoid the consequences of over- or under-treatment.
  • Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing, or discontinuing THYQUIDITY.
  • Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in postmenopausal women. To mitigate this risk, patients receiving THYQUIDITY should be given the minimum dose necessary that achieves the desired response.
  • Adverse reactions associated with THYQUIDITY therapy are primarily those of hyperthyroidism due to therapeutic overdosage.
  • Many drugs and some foods affect thyroid hormone pharmacokinetics and metabolism and may alter the therapeutic response to THYQUIDITY. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs. Administer at least 4 hours before or after drugs that are known to interfere with absorption. Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect absorption. Prescribers should consult appropriate reference sources for additional information on drug or food interactions with THYQUIDITY.
  • Closely monitor patients from birth to 3 months of age receiving THYQUIDITY due to the potential for glycerol- induced gastrointestinal irritation resulting in vomiting and/or osmotic diarrhea.
  • THYQUIDITY should not be discontinued during pregnancy, and hypothyroidism diagnosed during pregnancy should be promptly treated. TSH levels may increase during pregnancy, so TSH should be monitored and THYQUIDITY dose adjusted as needed.

Please see: [https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214047s000lbl.pdf] for full US Prescribing Information including Boxed Warning.

About MannKind Corporation

MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of inhaled therapeutic products for patients with endocrine and orphan lung diseases. MannKind is currently commercializing Afrezza® (insulin human) Inhalation Powder, its 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.

About Vertice Pharma

Vertice Pharma is a specialty pharmaceutical company focused on improving patients’ health. Vertice Pharma develops, manufactures, markets, and distributes high-quality and affordable pharmaceutical products through its operating companies. Vertice Pharma has global headquarters in the United Kingdom and United States headquarters in New Jersey. For more information visit www.verticepharma.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.

References

  1. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-99. doi: 10.1210/jcem.87.2.8182. PMID: 11836274.
  2. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390(10101):1550-1562. https://pubmed.ncbi.nlm.nih.gov/28336049/
  3. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751. https://www.ncbi.nlm.nih.gov/pubmed/25266247.

Company Contact:

MannKind Corporation
818-661-5000
ir@mannkindcorp.com

Vertice Pharma
Kimberly Branch
kbranch@vistapharm.com
727-530-1633 x276


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Source: MannKind