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Insmed Incorporated Message Board

  • fudfighter3 fudfighter3 Dec 22, 2013 6:35 PM Flag

    A target population puzzle for Christmas

    Although a high proportion of the 30,000 CF patients in the US are infected with pseudomonas, and will presumably be prescribed Arikace instead of Tobi as the central therapy in the antibiotic regimen - Non-CF bronchiectasis is a different kettle of fish.

    Almost every one of the 250,000 in the US with Non-CF bronchiectasis could harbour a few pulmonary NTM. But while any infection in the lungs of a CF patient is serious, a patient with Non-CF bronchiectasis could have good immunity.

    Maybe the bronchiectasis will have to be so far advanced that the patient needs treatment for pneumonia before Arikace becomes an option.

    Having said that - while the 30,000 in the US with CF translates to only 70.000 worldwide, the 250,000 with Non-CF bronchiectasis would likely translate to around 5,000,000 worldwide, before deducting the number of patients with Tuberculosis.

    As Tuberculosis is more dangerous, every patient with Non-CF bronchiectasis who becomes infected would need treatment. But whereas the smaller proportion who actually need treatment for NTM will be given Arikace as the only approved therapy, there are far cheaper therapies than Arikace for routine TB infection.

    Multi-drug-resistant TB - 630,000 cases worldwide in 2011 - is a different matter.

    It requires combination therapy with five drugs, from a preference ranking of fourteen. An aminoglycoside (such as amikacin) is equal-first in order of preference.

    But the bloodstream offers a relatively inefficient route for delivering an antibiotic to pulmonary Tuberculosis, as the stronghold of the infection is usually a mass of dead cells etc. at the (wrong) airway end of the interstitial fluid.

    Aminoglycosides are classed by the WHO as "critically important antimicrobials". Proof that Arikace is better than injected amikacin at killing pulmonary NTM could have interesting implications for a label issued by any regulatory agency tasked with combating the threat of antimicrobial resistance.

    Merry Christmas :-)

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    • Here's the key eligibility criterion for the ongoing Arikace NTM clinical trial -

      [ Positive sputum culture obtained at screening visit with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with one dominant species. ]

      Here's the primary outcome measure -

      [ Change in semi-quantitative mycobacterial culture results from baseline to end of treatment ]

      Nobody is saying that if the clinical trial is successful Arikace will be approved for the treatment of pulmonary infection by those two species alone.

      The reasoning is that because other species of mycobacteria which cause pulmonary disease colonise the lungs in a similar manner to Mycobacterium avium complex and Mycobacterium abscessus - using the pulmonary macrophages (which are supposed to kill them) as safe havens against most antibiotics - proof that Arikace reduces the concentration of those two species will be predictive of its likely efficacy against infection by other species of mycobacteria susceptible to amikacin.

      But what reason could there be to exclude from that chain of reasoning the species of mycobacteria which causes Tuberculosis?

    • "A target population puzzle for Christmas" ...for Christmas, huh.

      What kind of person would even think to say such a thing? Much, much sadder than I had ever thought.

11.34May 23 4:00 PMEDT