Post by lakers on Nov 8, 2015 23:37:20 GMT -5
MannKind Corporation’s Pain Management Plans: Looking Back
MannKind’s inhaled insulin treatment Afrezza has been in the market for over four months. But its sales have been below expectations. The biopharmaceutical firm sold only $1.1 million worth of Afrezza in the first two months of launch. Jefferies analysts expect Afrezza sales to pick up in the third-quarter as MannKind and its marketing partner Sanofi gear up to launch an extensive advertising campaign.
MannKind Pain Management
MannKind plans to expand its Technosphere to pain management
Meanwhile, the Valencia-based company has said on various occasions that it would expand the use of its Technosphere technology in the pain management market. At the company’s Q1, 2015 conference call, MannKind CEO Hakan Edstrom said that the company would make a material progress in this direction within 12-18 months. He specifically mentioned migraines, a lucrative market considering over 37 million U.S. citizens suffer from migraines.
However, MannKind is not the first or only company looking to explore this market, notes Seeking Alpha contributor Looking For Diogenes. Today, the most commonly used treatment for migraines is triptan under different brand names, which was first introduced in 1990s. Triptan is already available in the forms of pills, injections, needleless injections, nasal sprays, and rectal suppositories.
Besides impacting blood vessels in the brain, triptan also causes constrictions in the arteries in the heart. That’s why MannKind might be concerned with the expansion of triptan or any other inhaled drug for migraine in a user’s lungs. In the past, MAP Pharmaceuticals, NuPathe, Teva Pharma, Alder Biopharmaceuticals and others have experimented with various migraine molecules, but without much success.
MannKind’s former partner still struggling
While MannKind continues to reiterate that it would expand its Technosphere into pain management category, it has already tried doing that via a partnership. In February 2012, MannKind partnered with Torrey Pines Institute for Molecular Studies to develop what was described as a breakthrough in pain medication.
The drug was supposed to use MannKind’s proprietary technology for dosing. Three years later, the Torrey Pines Institute is still struggling to recover from the recession. The clinical trials of the “pretty marvelous” medication were supposed to begin in 2013. MannKind has avoided mentioning that project while telling investors about its ambitious plans to get into the pain medication category.
www.valuewalk.com/2015/06/mannkind-pain-management/
Matt in early Aug 2015
the other program in pain has actually been in animals already, so it’s a bit ahead in that regard. But that one is a little different because we have multiple APIs we’re evaluating. We haven’t selected one yet and all of us coming from that animal model preclinical, pre-human work, but that’s already underway.
Torrey Pines employee also said the API has finished animal clinical trial in 2013 awaiting human trial. She said it worked wonderfully in animal and could not wait for human trial in 2014.
The pain management program is focused on the product that is intended to manage moderate-to-severe acute pain and is also in the technical feasibility phase. We have already prepared several prototype powders to formulate around a small number of active pharmaceutical ingredients or API, and we have evaluated some in preclinical models. The results have been actually very encouraging so far. The focus now is to select the optimal API and move to Investigational New Drug or IND-enabling studies.
abstracts.aaps.org/Verify/aaps2013/postersubmissions/T3083.pdf
Stability of Novel Pain Therapy Tetrapeptide TPI-23 in Technosphere® Inhalation Powder and
Identification of Related-Compounds by Liquid Chromatography/Mass Spectrometry
Y. Livson, E. Harris, K. Fabio, J. Guarneri
MannKind Corporation
Purpose
To evaluate the stability of TPI23 tetrapeptide WsSF-NH2 under room temperature and accelerated conditions in a Technosphere inhalation powder using HPLC, and to identify the major related-compounds present using LC/MS. Methods
TPI23/Na2FDKP Technosphere inhalation powder was prepared at 50% weight API and placed on stability under room temperature and accelerated stability conditions in open container and inhalation cartridges. LC/UV separation was carried out on a Phenomenex Kinetex 2.6 C18 column (150x3.0mm) column at a flow rate of 0.5mL/min with an analysis time of 50 minutes. Compounds were eluted using a linear gradient consisting of mobile phase A of water/tetrahydrofuran/trifluoroacetic acid/ammonium hydroxide (970/30/1/1 (v/v/v/v)) and mobile phase B of acetonitrile/methanol/isopropanol/trifluoroacetic acid (850/150/30/1 (v/v/v/v)). Initial assay and stability analyses were conducted on a Waters 2695 Separations Module equipped with a Waters 2487 Dual Absorbance Detector. Related- compounds were identified using HPLC coupled with an Agilent 1100 Trap XCT mass spectrometer and an Agilent 6210 TOF mass spectrometer. ESI mass spectra were acquired in positive ion mode with full scan monitoring. TPI23 was subjected to forced degradation conditions to confirm the identity of the impurities formed in the inhalation powder during the stability study.
Results
Samples stored at room temperature lost 3.3% TPI23 assay after 16 weeks in an open container and 0.7% assay after 4 weeks in cartridges. Samples stored under accelerated conditions were most susceptible to degradation, with TPI23 assay losses after 4 weeks of 7.6% (open dish) and 8% (cartridges). Five major impurities (A-E) were present at more than 0.15 area% (ADE increased, BC remained constant).
Conclusion
TPI23 in a 50% weight Technosphere inhalation powder was stable (>96%) for up to 16 weeks when stored at room temperature, whereas samples stored for 4 weeks under accelerated stability conditions lost about 8% API. Using LC/MS and forced degradation experiments, five related-compounds were identified.
Acknowledgement: TPI-23 was discovered by the Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL.
"It's actually pretty marvelous," Houghten said. "You can't (overdose) on this drug."
The drug is being developed in partnership with Mannkind Corp., which has created a small device that allows people to inhale medicine. By inhaling, the medicine can relieve pain quicker than through pill form, Houghten said.
"Our pain compound, if it all works out, ... if you can take that pain compound and just inhale within just 30 seconds to a minute, your pain will be alleviated," Houghten said. "So you can see that that can be a real important step."
The drug has been tested on two separate animal groups and Houghten said the drug will be tested on a third before going before the U.S. Food and Drug Administration, which must give approval for human trials.
Houghten said the unique nature of the drug could make it easier to get approval.
"You never really quite know," he said. "Right now, everything's looking really good. ... We can't get a high enough dose that causes a problem."
Patients also do not build up a tolerance to the medicine, whereas other pain relievers require patients to take more and more to get the same effect.
Houghten said he is thrilled with the drug's progress.
"In reality is if it's 2014 (before human testing), I'm still going to be happy," Houghten said. "I don't think it's going to be a problem with the FDA. It's very simple what we want to do, so we can show them clearly here's the effective dose, here's the toxic dose. That's 90 percent of it right there. It's effective and it's not toxic."
www.tcpalm.com/business/torrey-pines-could-begin-human-testing-of-new-pain-medication-in-2013-ep-383096049-331604552.html?d=mobile
MannKind’s inhaled insulin treatment Afrezza has been in the market for over four months. But its sales have been below expectations. The biopharmaceutical firm sold only $1.1 million worth of Afrezza in the first two months of launch. Jefferies analysts expect Afrezza sales to pick up in the third-quarter as MannKind and its marketing partner Sanofi gear up to launch an extensive advertising campaign.
MannKind Pain Management
MannKind plans to expand its Technosphere to pain management
Meanwhile, the Valencia-based company has said on various occasions that it would expand the use of its Technosphere technology in the pain management market. At the company’s Q1, 2015 conference call, MannKind CEO Hakan Edstrom said that the company would make a material progress in this direction within 12-18 months. He specifically mentioned migraines, a lucrative market considering over 37 million U.S. citizens suffer from migraines.
However, MannKind is not the first or only company looking to explore this market, notes Seeking Alpha contributor Looking For Diogenes. Today, the most commonly used treatment for migraines is triptan under different brand names, which was first introduced in 1990s. Triptan is already available in the forms of pills, injections, needleless injections, nasal sprays, and rectal suppositories.
Besides impacting blood vessels in the brain, triptan also causes constrictions in the arteries in the heart. That’s why MannKind might be concerned with the expansion of triptan or any other inhaled drug for migraine in a user’s lungs. In the past, MAP Pharmaceuticals, NuPathe, Teva Pharma, Alder Biopharmaceuticals and others have experimented with various migraine molecules, but without much success.
MannKind’s former partner still struggling
While MannKind continues to reiterate that it would expand its Technosphere into pain management category, it has already tried doing that via a partnership. In February 2012, MannKind partnered with Torrey Pines Institute for Molecular Studies to develop what was described as a breakthrough in pain medication.
The drug was supposed to use MannKind’s proprietary technology for dosing. Three years later, the Torrey Pines Institute is still struggling to recover from the recession. The clinical trials of the “pretty marvelous” medication were supposed to begin in 2013. MannKind has avoided mentioning that project while telling investors about its ambitious plans to get into the pain medication category.
www.valuewalk.com/2015/06/mannkind-pain-management/
Matt in early Aug 2015
the other program in pain has actually been in animals already, so it’s a bit ahead in that regard. But that one is a little different because we have multiple APIs we’re evaluating. We haven’t selected one yet and all of us coming from that animal model preclinical, pre-human work, but that’s already underway.
Torrey Pines employee also said the API has finished animal clinical trial in 2013 awaiting human trial. She said it worked wonderfully in animal and could not wait for human trial in 2014.
The pain management program is focused on the product that is intended to manage moderate-to-severe acute pain and is also in the technical feasibility phase. We have already prepared several prototype powders to formulate around a small number of active pharmaceutical ingredients or API, and we have evaluated some in preclinical models. The results have been actually very encouraging so far. The focus now is to select the optimal API and move to Investigational New Drug or IND-enabling studies.
abstracts.aaps.org/Verify/aaps2013/postersubmissions/T3083.pdf
Stability of Novel Pain Therapy Tetrapeptide TPI-23 in Technosphere® Inhalation Powder and
Identification of Related-Compounds by Liquid Chromatography/Mass Spectrometry
Y. Livson, E. Harris, K. Fabio, J. Guarneri
MannKind Corporation
Purpose
To evaluate the stability of TPI23 tetrapeptide WsSF-NH2 under room temperature and accelerated conditions in a Technosphere inhalation powder using HPLC, and to identify the major related-compounds present using LC/MS. Methods
TPI23/Na2FDKP Technosphere inhalation powder was prepared at 50% weight API and placed on stability under room temperature and accelerated stability conditions in open container and inhalation cartridges. LC/UV separation was carried out on a Phenomenex Kinetex 2.6 C18 column (150x3.0mm) column at a flow rate of 0.5mL/min with an analysis time of 50 minutes. Compounds were eluted using a linear gradient consisting of mobile phase A of water/tetrahydrofuran/trifluoroacetic acid/ammonium hydroxide (970/30/1/1 (v/v/v/v)) and mobile phase B of acetonitrile/methanol/isopropanol/trifluoroacetic acid (850/150/30/1 (v/v/v/v)). Initial assay and stability analyses were conducted on a Waters 2695 Separations Module equipped with a Waters 2487 Dual Absorbance Detector. Related- compounds were identified using HPLC coupled with an Agilent 1100 Trap XCT mass spectrometer and an Agilent 6210 TOF mass spectrometer. ESI mass spectra were acquired in positive ion mode with full scan monitoring. TPI23 was subjected to forced degradation conditions to confirm the identity of the impurities formed in the inhalation powder during the stability study.
Results
Samples stored at room temperature lost 3.3% TPI23 assay after 16 weeks in an open container and 0.7% assay after 4 weeks in cartridges. Samples stored under accelerated conditions were most susceptible to degradation, with TPI23 assay losses after 4 weeks of 7.6% (open dish) and 8% (cartridges). Five major impurities (A-E) were present at more than 0.15 area% (ADE increased, BC remained constant).
Conclusion
TPI23 in a 50% weight Technosphere inhalation powder was stable (>96%) for up to 16 weeks when stored at room temperature, whereas samples stored for 4 weeks under accelerated stability conditions lost about 8% API. Using LC/MS and forced degradation experiments, five related-compounds were identified.
Acknowledgement: TPI-23 was discovered by the Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL.
"It's actually pretty marvelous," Houghten said. "You can't (overdose) on this drug."
The drug is being developed in partnership with Mannkind Corp., which has created a small device that allows people to inhale medicine. By inhaling, the medicine can relieve pain quicker than through pill form, Houghten said.
"Our pain compound, if it all works out, ... if you can take that pain compound and just inhale within just 30 seconds to a minute, your pain will be alleviated," Houghten said. "So you can see that that can be a real important step."
The drug has been tested on two separate animal groups and Houghten said the drug will be tested on a third before going before the U.S. Food and Drug Administration, which must give approval for human trials.
Houghten said the unique nature of the drug could make it easier to get approval.
"You never really quite know," he said. "Right now, everything's looking really good. ... We can't get a high enough dose that causes a problem."
Patients also do not build up a tolerance to the medicine, whereas other pain relievers require patients to take more and more to get the same effect.
Houghten said he is thrilled with the drug's progress.
"In reality is if it's 2014 (before human testing), I'm still going to be happy," Houghten said. "I don't think it's going to be a problem with the FDA. It's very simple what we want to do, so we can show them clearly here's the effective dose, here's the toxic dose. That's 90 percent of it right there. It's effective and it's not toxic."
www.tcpalm.com/business/torrey-pines-could-begin-human-testing-of-new-pain-medication-in-2013-ep-383096049-331604552.html?d=mobile
