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Insmed Incorporated Message Board

  • rehdvm2004 rehdvm2004 Jan 27, 2013 10:02 AM Flag

    Worst Case Scenario v. Best Case Scenario v. In Between - Arikace

    I do not see a worst case scenario for total failure because of the two-fold clinical effect. Improved FEV-1 and the probability that Arikace is going to kill lots of different bacteria. Not just Pa. My real hope is for NTM.

    The intermediate scenario is that the combined clinical endpoints of FEV-1 and bacterial kill are not in sych and EMEA and FDA ask for more numbers. Many posters on this MB think that only FEV - 1 counts. It does not. Transave/INSM calls this drug an "antibiotic" which means it must kill bacteria in statistically significant numbers. EOS. I think it should meet that criteria, but the in vitro data associated with culture and sensitivity testing will prevail. As for NTM, the intermediate scenario is that the full 84 days of treatment are necessary go get zero bacterial count in a patient and sustain that count for an important period of time (say 2 months to exacerbation). But exacerbation is going to also be dependent on ridding the sinuses of the head (maxillary and frontal) of NTM that might re-infect the person. I think untimately that simultanous treatment with Arikace and another systemic antibiotic at the same time will rid the person of NTM.

    The best case scenario for Arikace is that INSM meets all its clinical trial milestones and Arikace becomes a rotational drug in the physicians' regimen for treating Pa and a break through antibiotic for treatment of NTM. The former will ultimately lots of annual revenue in competition with other antibiotics, but the latter will be a free standing license to generate significant revenues. This would be an exclusive orphan drug approval which is years of independent revenues. I look to Arikace to cause zero NTM after 30 days of use. That means at least two negative NTM cultures after 21 and 28 days of treatment. The thumb rule, which is often ignored is that there be at least 4 days of no bacteria cultured to designate "cure." So a negative culture at Day 21 might mean the bacteria was eradicated on Day 20, so you have to reculture at Day 28 to achieve the clinical standard of 4 days with no bacteria. This is the same for human and veterinary medicine. This scenario seems to me to have a 2 year (NTM) to 4 year (Pa) time frame. This is a competetive pathway because again, typing in "inhalation antibiotic" at Clinical Trials gets 161 trials. There is no proprietary position clinical position in inhaling an antibiotic. Lots of the big biopharmas are in this area of clinical development.

    The wild scenario is that INSM hooks-up with a "pneumonia" expert physician and performs preclinical safety studies to get a MERSA and other types of life threatening infectious pulmonary disease. My father-in-law developed MERSA in his sinuses during the last 90 days of his life and systemic antibiotic did not do the job. He was on inhaled oxygen, but no antibiotic. I think that inhaled antibiotic in conjunction with systemic antibiotic would have cleared his sinuses sooner. Just the biophysics of medicine. But (contrary to posts on this MB) pneumonia is NOT respiratory infection. Pneumonia has a secretory component and "bio junk" builds-up in the lungs. That "bio-junk" blocks antibiotic contact with the bacteria, but also must be cleared from the lungs to not obstruct the breathing passages (bronchi, secondary bronchi, bronchioles and alveolar bronchioles). The respiratory "tree" produces no oxygen absorption or carbon dioxide effluent. It only conducts air to the alveoli which are the absorption/discharge structures. But if you look up the difference between "respiratory infection" and "pneumonia" there is a ton of difference clinically. There are not classifications like hemorrhagic, fibrinous, purulent, granulomatous, etc. for "respiratory infection." That is just the colonization of the respiratory tree with infective agents that could lead to pneumonia. It just so happens that CF patients are predisposed to respiratory infections, which is why Arikace is targeted as an "orphan indication antibiotic." If the whole world of "pneumonia" was the intended target, there would be hundreds of bacteria cultured and thousands of patients. The extension of a label copy for any drug is a case-by-case proposition. It is not a "right" from one orhan drug approval.

    So I think Arikace also will be approved in time. I hope most for NTM hitting a major clinical milestone soon, but Mother Nature and Father Time rule in this business.

    GLTAL

    The sky's the limit scenario for Arikace is that INSM start to

    Sentiment: Buy

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    • I do not see a worst case scenario for total failure because of the two-fold clinical effect. Improved FEV-1 and the probability that Arikace is going to kill lots of different bacteria. Not just Pa. My real hope is for NTM.

      The intermediate scenario is that the combined clinical endpoints of FEV-1 and bacterial kill are not in sych and EMEA and FDA ask for more numbers. Many posters on this MB think that only FEV - 1 counts. It does not. Transave/INSM calls this drug an "antibiotic" which means it must kill bacteria in statistically significant numbers. EOS. I think it should meet that criteria, but the in vitro data associated with culture and sensitivity testing will prevail. As for NTM, the intermediate scenario is that the full 84 days of treatment are necessary go get zero bacterial count in a patient and sustain that count for an important period of time (say 2 months to exacerbation). But exacerbation is going to also be dependent on ridding the sinuses of the head (maxillary and frontal) of NTM that might re-infect the person. I think untimately that simultanous treatment with Arikace and another systemic antibiotic at the same time will rid the person of NTM.

      The best case scenario for Arikace is that INSM meets all its clinical trial milestones and Arikace becomes a rotational drug in the physicians' regimen for treating Pa and a break through antibiotic for treatment of NTM. The former will ultimately lots of annual revenue in competition with other antibiotics, but the latter will be a free standing license to generate significant revenues. This would be an exclusive orphan drug approval which is years of independent revenues. I look to Arikace to cause zero NTM after 30 days of use. That means at least two negative NTM cultures after 21 and 28 days of treatment. The thumb rule, which is often ignored is that there be at least 4 days of no bacteria cultured to designate "cure." So a negative culture at Day 21 might mean the bacteria was eradicated o

    • I do not see a worst case scenario for total failure because of the two-fold clinical effect. Improved FEV-1 and the probability that Arikace is going to kill lots of different bacteria. Not just Pa. My real hope is for NTM.

      The intermediate scenario is that the combined clinical endpoints of FEV-1 and bacterial kill are not in sych and EMEA and FDA ask for more numbers. Many posters on this MB think that only FEV - 1 counts. It does not. Transave/INSM calls this drug an "antibiotic" which means it must kill bacteria in statistically significant numbers. EOS. I think it should meet that criteria, but the in vitro data associated with culture and sensitivity testing will prevail. As for NTM, the intermediate scenario is that the full 84 days of treatment are necessary go get zero bacterial count in a patient and sustain that count for an important period of time (say 2 months to exacerbation). But exacerbation is going to also be dependent on ridding the sinuses of the head (maxillary and frontal) of NTM that might re-infect the person. I think untimately that simultanous treatment with Arikace and another systemic antibiotic at the same time will rid the person of NTM.

      The best case scenario for Arikace is that INSM meets all its clinical trial milestones and Arikace becomes a rotational drug in the physicians' regimen for treating Pa and a break through antibiotic for treatment of NTM. The former will ultimately lots of annual revenue in competition with other antibiotics, but the latter will be a free standing license to generate significant revenues. This would be an exclusive orphan drug approval which is years of independent revenues. I look to Arikace to cause zero NTM after 30 days of use. That means at least two negative NTM cultures after 21 and 28 days of treatment. The thumb rule, which is often ignored is that there be at least 4 days of no bacteria cultured to designate "cure." So a negative culture at Day 21 might mean the bacteria was eradicated on Day 20, so you have to reculture at Day 28 to achieve the clinical standard of 4 days with no bacteria. This is the same for human and veterinary medicine. This scenario seems to me to have a 2 year (NTM) to 4 year (Pa) time frame. This is a competetive pathway because again, typing in "inhalation antibiotic" at Clinical Trials gets 161 trials. There is no proprietary position clinical position in inhaling an antibiotic. Lots of the big biopharmas are in this area of clinical development.

      The wild scenario is that INSM hooks-up with a "pneumonia" expert physician and performs preclinical safety studies to get a MERSA and other types of life threatening infectious pulmonary disease. My father-in-law developed MERSA in his sinuses during the last 90 days of his life and systemic antibiotic did not do the job. He was on inhaled oxygen, but no antibiotic. I think that inhaled antibiotic in conjunction with systemic antibiotic would have cleared his sinuses sooner. Just the biophysics of medicine. But (contrary to posts on this MB) pneumonia is NOT respiratory infection. Pneumonia has a secretory component and "bio junk" builds-up in the lungs. That "bio-junk" blocks antibiotic contact with the bacteria, but also must be cleared from the lungs to not obstruct the breathing passages (bronchi, secondary bronchi, bronchioles and alveolar bronchioles). The respiratory "tree" produces no oxygen absorption or carbon dioxide effluent. It only conducts air to the alveoli which are the absorption/discharge structures. But if you look up the difference between "respiratory infection" and "pneumonia" there is a ton of difference clinically. There are not classifications like hemorrhagic, fibrinous, purulent, granulomatous, etc. for "respiratory infection." That is just the colonization of the respiratory tree with infective agents that could lead to pneumonia. It just so happens that CF patients are predisposed to respiratory infections, which is why Arikace is targeted as an "orphan indication antibiotic." If the whole world of "pneumonia" was the intended target, there would be hundreds of bacteria cultured and thousands of patients. The extension of a label copy for any drug is a case-by-case proposition. It is not a "right" from one orhan drug approval.

      So I think Arikace also will be approved in time. I hope most for NTM hitting a major clinical milestone soon, but Mother Nature and Father Time rule in this business.

      GLTAL

 
INSM
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