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Insmed Incorporated Message Board

  • fudfighter3 fudfighter3 Jan 21, 2014 11:13 AM Flag

    Approved use of Arikace in the US and Europe?

    The Company guidance for some time has been that they intend to ask for FDA and EMA labels for Arikace based upon the totality of the data from all of the Arikace studies.

    The following extract from the Q3 report is confirmation -

    [ In addition, during October 2013 Insmed commenced the Scientific Advice Working Party (SAWP) process with the European Medicines Agency (EMA) and expects to have discussions with the EMA regarding ARIKACE for NTM lung disease during the fourth quarter of 2013. ]

    Much now hinges upon the data from the NTM study due this quarter.

    But we do know that -

    1. Amikacin injection is a proven therapy both for pulmonary NTM infection and multi-drug-resistant Tuberculosis

    2. Arikace has proven efficacy at Phase III in delivering amikacin to a pulmonary infection.

    If this data does indeed demonstrate that Arikace can eradicate amikacin-susceptible Mycobacterium avium complex and Mycobacterium abscessus from their strongholds in the pulmonary macrophages - why would anybody expect amikacin-susceptible Mycobacterium Tuberculosis to fare any differently?

    Coupled with proof at Phase III that Arikace delivered its amikacin payload even in the congested lungs of a CF patient - why wouldn't the FDA and the EMA both approve Arikace as a therapy for serious pulmonary infection by amikacin-susceptible pathogens?

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    • Given that such a high proportion of MDR-TB occurs elsewhere than in countries with a reasonable standard of healthcare it's not a safe assumption that Arikace will be widely used in that indication any time soon.

      But provided the data due this quarter from the NTM study is sufficiently compelling there will be a powerful incentive to use Arikace in MDR-TB if it has the potential to shorten the currently-recommended eighteen month five-drug therapeutic regimen, as aminoglycoside injection is currently equal-first in order of preference.

      Of the estimated 630,000 cases of MDR-TB Worldwide each year 120,000 are attributed to China, which has been spending billions on healthcare improvement in recent years and is predicted to be spending $1 trillion annually on healthcare by 2020.

      The estimated 110,000 with diagnosed with NTM in the US, Europe and Japan each year are currently treated with off-label therapies, including amikacin injection - a captive market for Arikace until another antibiotic is approved.

      For the estimated 65,000 with Cystic Fibrosis in the US and Europe, twice-daily tobramycin inhalation solution has traditionally been the most widely-used antibiotic.

      The more recent inhalation powder formulation is far more convenient than the inhalation solution. But the side effects are significantly worse - and it's ineffective against strains of bacteria which have evolved resistance to tobramycin as a result of poor compliance with the traditional regimen - and the recommended daily regimen of eight capsules of powder is not the solution to the problem of increasing antimicrobial resistance through poor compliance.

      The once-daily Arikace regimen will surely become the central therapy in the antibiotic regimen for this patient population just as soon as physicians are able to prescribe it.

      • 2 Replies to fudfighter3
      • Unsurprisingly - 27% of the clinical trial participants taking the powder formulation dropped out early, whereas only 18% of those taking the solution formulation did so.

        Even FDA personnel publicly voiced their concerns that the powder formulation was no more effective than the PLACEBO in one of the clinical trials, and that it was associated with more side effects than was the solution formulation -

        [ In documents released ahead of an FDA panel meeting September 5, agency staff questioned whether Novartis' inhaled antibiotic powder tobramycin, dubbed TIP, improved lung function in patients with cystic fibrosis, or whether it is as safe and effective as the current version of the product ...

        "The sustainability of improvements in (lung function) found...may raise concern regarding the clinical significance of these findings," FDA staff wrote. ]

        [ Of the two placebo-controlled trials provided, results from one showed TIP improved lung function more than placebo, but the other study failed to meet its goal of demonstrating a statistically significant improvement in lung function.

        FDA staff noted that patients receiving TIP reported more side effects ]

        TIP % vs TIS %

        48.40 ... 31.10 ... Cough
        33.80 ... 30.10 ... Lung disorder / exacerbation
        18.20 ... 19.60 ... Productive cough
        15.60 ... 12.40 ... Dyspnea
        15.60 ... 12.40 ... Pyrexia
        14.00 ... 10.50 ... Oropharyngeal pain
        13.60 ... 03.80 ... Dysphonia
        13.00 ... 12.40 ... Hemoptysis
        11.40 ... 12.00 ... Headache
        08.10 ... 07.20 ... Nasal congestion
        07.50 ... 09.60 ... Nausea
        07.10 ... 06.20 ... Rales
        06.80 ... 06.20 ... Wheezing
        06.50 ... 02.90 ... Chest discomfort
        06.20 ... 05.70 ... Vomiting
        04.50 ... 01.90 ... Throat irritation
        04.20 ... 01.90 ... Diarrhea
        03.90 ... 00.50 ... Dysgeusia
        02.60 ... 01.90 ... Epistaxis
        02.30 ... 02.40 ... Rash
        01.60 ... 00.50 ... Bronchospasm

        01.90 ... 02.40 ... Tinnitus
        01.00 ... 00.50 ... Hearing loss

        03.90 ... 01.00 ... FEV-1 deterioration

        27.00 ... 18.00 ... Discontinuation

      • Totally FALSE . the Podhaler data shows CONSISTENTLY in line safety data as with other regimes.Your post is FALSE. The convenience safety and compliance of the podhaler is why Novartis will control the CF market in the world within the time Insmed hopes to get a limited entry in the world approximately 16 months. Move on jrk

    • You could also argue, since physicians can prescribe an approved therapy off label, the FDA wouldn't need to provide such a broad approval for Arikace once they have approved the therapy for one condition.

      • 5 Replies to x10bagger
      • One observation in particular last year was particularly illuminating -

        "IV amikacin is used to treat this patient population right now. You can't get enough amikacin into the lung through IV to successfully address this disease."

        Given that the aminoglycosides are classed as Critically Important Antimicrobials - assuming the NTM data is OK, a good way to reduce the opportunity for aminoglycoside-resistant strains of bacteria to evolve would be to approve Arikace for the treatment of all amikacin-susceptible pulmonary infections for which physicians are currently prescribing amikacin injection.

        And given that Tobi is also an aminoglycoside, I'm sure the medical community would much prefer CF patients to use once-daily Arikace rather than the eight capsules a day TIP - a regimen which is unlikely to be rigorously adhered to by many patients if the development of tobramycin resistance within the CF patient population is anything to go by.

        Today's tobramycin resistance is tomorrow's aminoglycoside resistance.

      • 2 things wrong. Insmed launch will be limited to overseas and they will need to trial for a label expansion.Novartis will own most of the world by the time 2016 rolls around( when Arikace will see some limited use )

      • 140 characters, re your prediction -

        "Novartis will own most of the world by the time 2016 rolls around".

        - I'm sure you must be aware of this warning on the TIP packaging -

        [ Coughing up blood (very common) ]

        "Very common" is defined as affecting more than one patient in ten. But at face value that could mean nine out of every ten patients who (for the moment) use that Novartis drug cough up blood.

        Would you mind telling us what proportion of patients inhaling TIP reported coughing up blood?

        And was the recorded incidence based upon studies where the subjects skipped doses as often as they do in everyday life?

        If so - do you think a far higher proportion would be coughing up blood if every patient took all eight capsules a day?

      • 2 things wrong. Insmed launch will be limited to overseas and they will need to trial for a label expansion.Novartis will own most of the world by the time 2016 rolls around( when Arikace will see some limited use )

      • True. But I'd expect the FDA and EMA to be looking at this more from the viewpoint of combating the threat posed by strains of bacteria which have evolved with resistance to commonly-used antibiotics.

        Aminoglycosides are classed by the WHO as Critically Important Antimicrobials. It would be madness for the FDA and EMA to do anything which would encourage physicians to continue to prescribe amikacin injection as a therapy for pulmonary infections.

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