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Post by mango on Sept 11, 2017 14:01:55 GMT -5
MannKind Bucket #1
 • Tobramycin—Systemic use is limited to intravenous and intramuscular administration due to the poor absorption of current inhaled therapy via nebulization (TOBI) & TOBI Podhaler (DPI). I suspect MannKind's formulation would have greater systemic absorption than TOBI, but I am making an assumption by saying that as I haven't looked any data of their's with Tobramycin (is there any?). —Based on MannKind's science I would think it could be superior to all current formulations. —Potential for OTC. In some countries it is sold OTC. United States and Canada is prescription only. • Systemic Indications: Aerobic Gram-positiveStaphylococcus aureus Aerobic Gram-negative1. 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. Pseudomonas in CF patients • Potential Indications/Off Label Use: 1. CF patients with gram-negatives other than Paeudomonas? 2. Non-CF patients with bronchiectasis? 3. Non-CF patiets with Pseudomonas? 4. Sinusitus? 5. Ages < 6 years old? • Safety and Efficacy that has Not Been Established On: 1. < 6 years old 2. FEV1 < 25% or > 80% predicted 3. Patiens with Burkholderia cepacia • Concerns 1. Tobramycin is ototoxic (primarily vestibulotoxic) 2. Tobramycin is nephrotoxic • Questions 1. Can MannKind's formulations potentially be less ototoxic and/or nephrotoxic? I currently don't take antibiotics because of ototoxicity so it would sure be nice if MannKind's formulation diminished this concern. Maybe I am dreaming. 2. Can MannKind's formulation be used for systemic conditions? 3. Can MannKind's formulation potentially be used for Ophthalmic conditions? 4. Can MannKind's formulation potentially be sold OTC? 5. For fun, what would you want MannKind to call their Tobramycin formulation? I like TOBRAZZE, TOBRAZZA, and MYCINHALER • DNA
—Inhaled Therapeutic Nucleic Acid
1. Gene therapy
2. Cancers
3. Viruses
4. Pulmonary diseases
—Currently, the best way to administer inhaled nucleic acids (such as plasmid DNA and small interfering RNA) is with a dry powder formulation. Liquid aerosol formulations all have demonstrated poor stability. Dry powder formulation will be the preferred choice. MannKind has the science necessary to develop dry powder formulations with superior stability and safety and efficacy than anyone else.
—TechnoVax VLPs lack a nucleic acid, but I am wondering if they can still fall under this category. Thoughts?
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Post by dreamboatcruise on Sept 11, 2017 14:15:43 GMT -5
What is DNase?
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Post by mango on Sept 11, 2017 14:28:04 GMT -5
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Post by porkini on Sept 11, 2017 14:29:48 GMT -5
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Post by mango on Sept 11, 2017 14:31:28 GMT -5
Ah I see. I'm an idiot. Hmm ok so what's that used for? Purifying in protein extraction? |
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Post by mango on Sept 11, 2017 14:35:57 GMT -5
Ah I see. I'm an idiot. Hmm ok so what's that used for? Purifying in protein extraction? That sucks. I liked the idea of them doing inhaled dry powder nucleic acids. |
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Post by peppy on Sept 11, 2017 14:47:22 GMT -5
Deoxyribonuclease (pronounced "dee-oxy-rybo-noo-clee-ase"), or recombinant human deoxyribonuclease 1 (rhDNase or DNase), is an experimental drug used to treat cystic fibrosis (CF), an inherited lung disease. People with CF experience chronic (constant) and increasingly worse symptoms throughout their lives. CF patients often die in their late twenties. CF treatment has usually meant antibiotics and chest therapy (a physical pounding on the chest to loosen accumulated fluids). DNase Scientists discovered that the mucus (slimy secretion) of CF patients is full of DNA, which spills out of white blood cells as they die. DNase is an enzyme (a protein-like substance) that cuts the DNA present in the mucus. At first DNase was made from cows, but many patients had allergic reactions to it. Then a company separated the gene for human deoxyribonuclease, which chops up the protein but does not cause allergic reactions. DNase is delivered to the patient in aerosol form, and it improves lung function by breaking up the thick mucus in the lungs. The patient is then able to clear the lungs by coughing. Considered among the ten most important advances of 1993—the year the drug was approved by the Food and Drug Administration (FDA)—it is also being considered for the treatment of chronic bronchitis. Read more: www.discoveriesinmedicine.com/Com-En/Deoxyribonuclease.html#ixzz4sOwjGQyP |
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Post by mango on Sept 11, 2017 14:49:06 GMT -5
Deoxyribonuclease (pronounced "dee-oxy-rybo-noo-clee-ase"), or recombinant human deoxyribonuclease 1 (rhDNase or DNase), is an experimental drug used to treat cystic fibrosis (CF), an inherited lung disease. People with CF experience chronic (constant) and increasingly worse symptoms throughout their lives. CF patients often die in their late twenties. CF treatment has usually meant antibiotics and chest therapy (a physical pounding on the chest to loosen accumulated fluids). DNase Scientists discovered that the mucus (slimy secretion) of CF patients is full of DNA, which spills out of white blood cells as they die. DNase is an enzyme (a protein-like substance) that cuts the DNA present in the mucus. At first DNase was made from cows, but many patients had allergic reactions to it. Then a company separated the gene for human deoxyribonuclease, which chops up the protein but does not cause allergic reactions. DNase is delivered to the patient in aerosol form, and it improves lung function by breaking up the thick mucus in the lungs. The patient is then able to clear the lungs by coughing. Considered among the ten most important advances of 1993—the year the drug was approved by the Food and Drug Administration (FDA)—it is also being considered for the treatment of chronic bronchitis. Read more: www.discoveriesinmedicine.com/Com-En/Deoxyribonuclease.html#ixzz4sOwjGQyPSo it could be combined with Tobramycin for CF? |
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Post by mango on Sept 11, 2017 14:52:08 GMT -5
Deoxyribonuclease (pronounced "dee-oxy-rybo-noo-clee-ase"), or recombinant human deoxyribonuclease 1 (rhDNase or DNase), is an experimental drug used to treat cystic fibrosis (CF), an inherited lung disease. People with CF experience chronic (constant) and increasingly worse symptoms throughout their lives. CF patients often die in their late twenties. CF treatment has usually meant antibiotics and chest therapy (a physical pounding on the chest to loosen accumulated fluids). DNase Scientists discovered that the mucus (slimy secretion) of CF patients is full of DNA, which spills out of white blood cells as they die. DNase is an enzyme (a protein-like substance) that cuts the DNA present in the mucus. At first DNase was made from cows, but many patients had allergic reactions to it. Then a company separated the gene for human deoxyribonuclease, which chops up the protein but does not cause allergic reactions. DNase is delivered to the patient in aerosol form, and it improves lung function by breaking up the thick mucus in the lungs. The patient is then able to clear the lungs by coughing. Considered among the ten most important advances of 1993—the year the drug was approved by the Food and Drug Administration (FDA)—it is also being considered for the treatment of chronic bronchitis. Read more: www.discoveriesinmedicine.com/Com-En/Deoxyribonuclease.html#ixzz4sOwjGQyPdornase alfa |
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Post by peppy on Sept 11, 2017 15:07:50 GMT -5
Deoxyribonuclease (pronounced "dee-oxy-rybo-noo-clee-ase"), or recombinant human deoxyribonuclease 1 (rhDNase or DNase), is an experimental drug used to treat cystic fibrosis (CF), an inherited lung disease. People with CF experience chronic (constant) and increasingly worse symptoms throughout their lives. CF patients often die in their late twenties. CF treatment has usually meant antibiotics and chest therapy (a physical pounding on the chest to loosen accumulated fluids). DNase Scientists discovered that the mucus (slimy secretion) of CF patients is full of DNA, which spills out of white blood cells as they die. DNase is an enzyme (a protein-like substance) that cuts the DNA present in the mucus. At first DNase was made from cows, but many patients had allergic reactions to it. Then a company separated the gene for human deoxyribonuclease, which chops up the protein but does not cause allergic reactions. DNase is delivered to the patient in aerosol form, and it improves lung function by breaking up the thick mucus in the lungs. The patient is then able to clear the lungs by coughing. Considered among the ten most important advances of 1993—the year the drug was approved by the Food and Drug Administration (FDA)—it is also being considered for the treatment of chronic bronchitis. Read more: www.discoveriesinmedicine.com/Com-En/Deoxyribonuclease.html#ixzz4sOwjGQyPdornase alfa got it. www.pulmozyme.com/ a nebulizer www.pulmozyme.com/taking-pulmozyme-and-nebulizers-for-CF#
Not enough to have sanofi, novo, and Lilly protecting their profits; let's go after Genentech.
I see what Ray is doing, cancer is easier. The pharmaceuticals are terrible, and the complaints do not last long.
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Post by dreamboatcruise on Sept 11, 2017 15:41:17 GMT -5
peppy... thanks. Now it makes sense.
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Post by mango on Sept 11, 2017 17:33:24 GMT -5
A MannKind-made inhaled dry powder Tobramycin formulation coupled with a MannKind inhaler would become the preferred choice for many reasons.
First, Novartis' Podhaler sucks.
• It is not a high resistant inhaler
• The inhaler is not user friendly
• The inhaler requires too many steps to use
• It is common for pieces of the capsule to become inhaled by the patient (via the capsule puncture). This is a major problem.
• 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
• CF patients need an inhaler they can throw away right after using. The Podhaler is used for 7 days. This poses too many potential problems.
• Piercing a capsule with a button is ridiculous. If you press the button more than once more pieces of the capsule risk being inhaled.
• 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 prone to errors for children to effectively use without supervision.
• There is an unmet need for a once daily, single use dry powder Tobramycin inhaler that is also safe, effective and patient-friendly. This would allow for bacterial suppression during dosing intervals and would 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 inhaler decreases cough severity via requiring lower inspiratory flow rates.
I think different fixed dose combinations incorporating a quorum sensing inhibitor is needed.
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