Aerosolized Antibiotics & Selling Nebulizers

“The medicine comes for free, just pay us for the inhaler” should be the marketing slogan for this group of therapeutics.  Nebulizers are good business: hard to copy as a delivery system, they are a great opportunity to ‘evergreen’ off-patent antibiotics.

The inhalational route to administer antibiotics is clearly attractive.  The ease of delivery, the much reduced systemic exposure, and high local concentrations at the site of infection are major advantages over pills.   Remember the days when inhaled pentamidine was used for prophylaxis of P. carinii  (P. jiroveci) pneumonia?  This otherwise toxic drug was reasonably well tolerated by the respiratory route, and with clear benefits to patients.

Hence, there are good reasons to belief that antibiotics given by the pulmonary route will work for other pulmonary infections as well.  Problems for developers are mainly related to local tolerability and the technical issues of controlling particle size, hygroscopicity, and dose-metering, not so much safety concerns.

As it turns out, proving the efficacy of inhaled antibiotics is not a trivial pursuit.  The precedent-setting TOBI (tobramycin PodHaler) for cystic fibrosis, has paved the way for the entire ‘genre’ of drugs now in the pipeline showing  how functional improvement (FEV1) is the efficacy marker required for approval.  Hence, it is FEV1 , not microbiologic eradication (which is not achievable) or reduction in CFU/mL (which is achievable) that companies use as primary efficacy endpoint as far as I can tell.

The commercial success of TOBI (approx.  USD 300-400 mio/year) is quite impressive.  Approved by FDA in 1997, it is just the right incentive for small companies to pursue respiratory delivery systems.  Nonetheless, so far, only 1 other inhaled antibiotic has been approved in the US:  In 2010, Cayston (inhaled aztreonam) was approved after a long gestation period at FDA and a bitterly fought battle between Gilead and regulators.

Here the inhalational drugs in development  I was able to find:

Product NameDrugCompanyInhalerIndication
AeroVancVancomycinSavara Pharmaceuticalsproprietary DPICF with MRSA
Amikacin InhaleAmikacinBayer / NektarNektar's Pulmonary Drug Delivery System (PDDS)VAP adjunctive
ArikayceAmikacin / liposomalInsmed PharmaceuticalsOptimized PARI investigational eFlow® Nebulizer SystemCF, NTM
Ciprofloxacin DPICiprofloxacinBayer HealthCareNovartis' PulmoSphere™ technology T-326 DPINon-Cystic Fibrosis Bronchiectasis
N.N.Amikacin + fosfomycinCardeas PharmaPARI Investigational eFlow® Inline NebulizerVAP adjunctive
Pulmaquin / LipoquinCiprofloxacin / liposomalAradigm PharmaceuticalsAERx inhalerBronchiectasis, CF, COPD, biodefense

As you will notice, these are not like your grandma’s Ventolin inhalers any more: they are high-tech devices featuring breath-activated delivery and high efficiency reliable drug delivery.  And some look pretty slick too.

However, it is hard to understand why all of them garnered QIDP status.  Should the next 10 quinolones and aminoglycosides all get a patent extension just for doing a CF study,with a new inhaler of course?

Nonetheless, I am glad to see vancomycin and fosfomycin on the list of inhaled antibiotics undergoing development.  Maybe other drug classes will join the list as well.  I am thinking of antifungals (like amphotericin for pulmonary aspergillosis), or the new antivirals (for RSV bronchiolitis).  There certainly are markets for these indications, bundled with a new inhaler, of course.

 

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