A problem has been the non-tuberculous mycobacterial pathogens are not as easily treated as routine cases of tuberculosis and therapy for these patients generally involves multiple medications, which are associated with multiple toxicities, are very expensive and have to be given over usually an 18 to 24 months period of time.
Treatment for MDR-TB must be given for a minimum of 18 months ... It is not unusual for patients with MDR-TB to be on treatment for two years or more.
Five drugs should be chosen in the following order (based on known sensitivities):
an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin)
a fluoroquinolone: e.g., moxifloxacin (ciprofloxacin should no longer be used);
a thioamide: prothionamide or ethionamide
a macrolide: e.g., clarithromycin
high-dose INH (if low-level resistance)
Insmed CEO Will Lewis (on NTM) -
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.
Diana Bilton, MD
I think what I'd just like to say is our excitement is around the fact that we have to use intravenous amikacin in a difficult cystic fibrosis, non-tuberculous mycobacteria and those non-CF . And that is often limited by the length of course by problems with audio-toxicity or renal toxicity particularly in the older patients. So, there is a read-through here in terms of the safety profile in this population.
I agree I don't think we can take things too far on bacterial numbers versus mycobacteria, they are different. But we know amikacin is an effective agent against mycobacteria and we limit it because we have it intravenously with toxicity over time. So that's the excitement for me as the possibility of a nebulized agent.
The WHO, EMEA, CDC, NIH and FDA have as a common objective the more efficient use of antibiotics - with the aim of reducing opportunities for drug-resistant strains of bacteria to evolve and spread.
From a CDC report this March on Carbapenem-Resistant Enterobacteriaceae -
"Untreatable and hard-to-treat infections from CRE germs are on the rise among patients in medical facilities. CRE germs have become resistant to all or nearly all the antibiotics we have today. Types of CRE include KPC and NDM."
"In addition to spreading among people, CRE easily spread their antibiotic resistance to other kinds of germs, making those potentially untreatable as well."
Some antibiotics are considered more important than others. From the World Health Organisation list of Critically Important Antimicrobials -
"Aminoglycosides (amikacin etc) - Sole or limited therapy as part of treatment of enterococcal endocarditis and Multi-Drug Resistant (MDR) tuberculosis."
Nobody at Insmed is likely to say anything which could be construed as an attempt to exert pressure on a regulatory agency. But mere common sense dictates that, provided the finding from the ongoing NTM clinical trial is that Arikace has delivered an effective concentration of amikacin to a pulmonary mycobacterial infection, neither the FDA nor the EMEA is going to issue a label for Arikace which DOESN'T include a pulmonary infection for which amikacin injection is routinely used.
The recent observation from Lewis on NTM therapy says it all -
"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."
IV amikacin is routinely used to treat serious infections by gram-negative bacteria (Pseudomonas, Klebsiella and others) and mycobacteria (MDR-TB and NTM). Of these, the only pathogens NOT specifically named in the QIDP legislation are NTM.
KPC (one of the CREs mentioned above) is Klebsiella pneumoniae carbapenemase.