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Post by harryx1 on Jan 12, 2019 14:26:36 GMT -5
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Post by mango on Jan 12, 2019 18:36:18 GMT -5
Novartis' TOBI PodHaler
• Is not a high resistant inhaler
• The inhaler is not user-friendly
• The inhaler requires numerous steps to use: treatment burden
• It is common for pieces of the capsule to become inhaled (via the capsule puncture)
• Piercing the capsule requires pushing a button. This is done only after you have:
1. Unscrewed the lid of the storage case
2. Unscrewed the mouthpiece of the inhaler
3. Placed a capsule in the chamber
4. Screwed the mouthpiece back on the inhaler
• Each dose consists of 4 individual capsules and requires for 2 inhalations per capsule
• Utilizes an inferior excipient
• Contains sulfuric acid
• People with CF need an inhaler that can be throw away immediately after using and/or an inhaler that requires minimal cleaning and maintance and is low risk for contamination. The Podhaler is used for 7 days and has many components, posing a risk for contamination and inducing bacterial infection in the person with CF
• Requiring a button-push to pierce the capsule poses high risk of breaking the capsule into tiny pieces and potentially inhaling them during treatment
• Much the powder is impacted in the mouth and the back of the throat
• Two inhalations per capsule is required because an inhaled volume of ≥ 1.2 L is required to empty the powder from the capsule.
• This drug/device combo is far too complex and burdensome, especially for a child to use without supervision. All these indicate that the currently available inhaled TOBI DPI is no where good enough
• There is an unmet need for a once daily, single use dry powder Tobramycin inhaler that is also safe, effective and user-friendly with no treatment burdens, This would allow for bacterial suppression during dosing intervals and would also help reduce the development of adaptive resistance. An inhalers resistance is a critical factor in the outcome of severity of cough in CF patients. A high resistance MannKind inhaler would decrease cough severity by requiring lower inspiratory flow rates and volumes.
Tobramycin
—Currently available inhaled options: nebulization via TOBI & TOBI Podhaler via DPI.
—Potential for OTC? In some countries Tobramycin is sold OTC. United States and Canada is prescription only.
• Systemic Indications
Aerobic Gram-positive
1. Staphylococcus aureus
Aerobic Gram-negative
1. Citrobacter
2. Enterobacter
3. Escherichia coli
4. Klebsiella
5. Morganella morganii
6. Pseudomonas aeruginosa
7. Proteus mirabilis
8. Proteus vulgaris
9. Providencia
10. Serratia
• Inhaled Indications:
1. P. aeruginosa in CF patients
• Potential Indications/Off Label Use:
1. CF patients with gram-negatives other than P. aeruginosa
2. Non-CF patients with bronchiectasis?
3. Non-CF patients with Pseudomonas?
4. Ages < 6 years old?
• Safety and Efficacy that has Not Been Established With Inhaled Tobramycin:
1. < 6 years old
2. FEV1 < 25% or > 80% predicted
3. Patients with Burkholderia cepacia
• Concerns
1. Tobramycin is ototoxic (primarily vestibulotoxic)
2. Tobramycin is nephrotoxic
—Solution: Inhaled antibiotics are associated with minimal systemic toxicity and adverse events compared with oral and IV.
• Question
Can MannKind's TobraT potentially be sold OTC?
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Post by mnholdem on Jan 12, 2019 22:42:45 GMT -5
mangoI must remind you that board rules state that you should include a link to sources when you copy/repost information. Thank you!
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Post by harryx1 on Jan 25, 2019 14:47:16 GMT -5
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Post by boca1girl on Jan 25, 2019 15:24:40 GMT -5
Harry, MNKD needs to hire you.
But on 2nd thought, ...”you don’t have to buy the cow when you get the milk for free”.. as “they” say.
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Post by mango on Jan 25, 2019 15:40:50 GMT -5
Harry, MNKD needs to hire you. But on 2nd thought, ...”you don’t have to buy the cow when you get the milk for free”.. as “they” say. I believe Harry and SlingVector make some really awesome, professional quality stuff. Way better and more effective than what the company could ever (legally) do themselves. |
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Post by mango on Jan 25, 2019 15:45:04 GMT -5
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene[snippet] The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene was identified in 1989 by geneticist Lap-Chee Tsui and his research team as the gene associated with cystic fibrosis (CF). Tsui’s research pinpointed the gene, some mutations to which cause CF, and it revealed the underlying disease mechanism. The CFTR gene encodes a protein in cell membranes in epithelial tissues and affects multiple organ systems in the human body. Mutations in the CFTR gene cause dysfunctional regulation of cell electrolytes and water content. Research on the CFTR mutation has shed light on the ways in which this gene is vital to normal human development. embryo.asu.edu/pages/cystic-fibrosis-transmembrane-conductance-regulator-cftr-gene
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Post by mango on Jan 25, 2019 15:49:30 GMT -5
Here is the company & the two inhaled CFTR-gene candidates that the Cystic Fibrosis Foundation mentioned in their tweet. Talee BioGene therapy for cystic fibrosis via inhalation has the potential to correct the CFTR defect and downstream pathophysiologic processes in the lung. All cystic fibrosis patients could be candidates for these treatments, regardless of the specific mutation. Talee is developing two inhaled gene therapy drug candidates to treat cystic fibrosis, TL-101 and TL-102. Both are designed to treat all cystic fibrosis patients, regardless of the specific CFTR mutation. TL-101• TL-101 is a recombinant AAV-based gene therapy to treat all forms of cystic fibrosis. TL-102• TL-102 is a lentiviral-based inhaled gene therapy to treat all forms of cystic fibrosis. taleebio.com/pipeline/ |
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Post by mango on Jan 25, 2019 16:12:52 GMT -5
AAV PlatformOur AAV platform is designed to solve several key issues that are holding back gene therapy treatment for cystic fibrosis. As such, it includes the following elements: 1. a highly functional CFTR minigene (CFTRΔR), 2. a highly active synthetic promoter (SP183) that drives high-level CFTR expression, 3. augmenters to significantly enhance AAV transduction by overcoming barriers of nuclear uptake in human airway epithelia, and 5. an evolved chimeric AAV vector that is highly tropic for the human airway (AV.TL65). Lentivirus PlatformOur lentiviral platform is a modified lentiviral vector technology that has the benefits of a large carrying capacity, high transduction efficiency, persistent expression, minimal immunogenicity, and genomic integration, thereby allowing transduced progenitor cells to indefinitely produce corrected airway epithelia without oncogenic risk. The vector is genetically engineered with an envelope protein which increases binding and entry to the surface of airway epithelial cells. Because it can effectively deliver large payloads without causing debilitating immune reactions, and because it integrates into the genome with minimal risk of genotoxicity, our lentiviral-based gene therapy treatment has the potential to be a single administration, long-lasting genetic treatment for cystic fibrosis. ManufacturingTalee is taking a multi-pronged approach to producing our products. We are utilizing the manufacturing facilities and expertise of our partners at the Children’s Hospital of Philadelphia (CHOP) and the University of Iowa and we are building our own in-house expertise and capability. Both the CHOP and Iowa facilities have been used successfully in numerous gene therapy clinical trials. taleebio.com/gene-therapy/
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