The NIAID would not have suggested an Arikace study using the NIH network of study centers without a reasonable expectation that the FDA would do something which would adequately recompense the NIAID for its considerable effort and expense.
The study was expected to provide evidence of reduction in bacterial load - suggestive of conversion to culture-negative with a longer period of therapy.
Instead the study delivered a 25% success rate in culture conversion in just twelve weeks -
18 of the 44 patients on Arikace recorded an improvement of one step or better - vs 13 of the 45 patients on placebo who did so.
Of the 18 patients on Arikace who recorded an improvement, 11 recorded the maximum number of steps of improvement possible for the patient to record - converting to culture-negative (clinically relevant).
As a result of the study hitting an endpoint which is clinically relevant the FDA ended up with data to support an application for Breakthrough Therapy Designation.
But the biggest clue as to the FDA's likely response has ALREADY been provided.
The GAIN legislation was intended to encourage the FDA to give a higher priority to drugs which could be used to counter the threat to public health posed by drug-resistant infectious pathogens. It empowered the FDA to use new "fast track" approval pathways.
Breakthrough Therapy is the fastest - allowing approval supported by data as early as Phase I.
Qualified Infectious Disease Product designation is another - and the FDA has already designated Arikace QIDP.
Why - when Insmed applied for the QIDP designation - didn't the FDA respond as follows?
"Sorry guys. The intention of the legislators was that we use QIDP to fast-track drugs to combat drug-resistant infectious pathogens which pose a threat to public health.
NTM isn't infectious. Arikace will just have to join the queue with all of the other drugs for diseases which are only a serious problem for a small number of people".
All facetiousness aside, here is an interesting fact. Not only is NTM a drug-resistant infectious disease, it also appears to be transmissible... from medpagetodayDOTcom:
"A bacterial species increasingly responsible for lung infections in cystic fibrosis patients can be transmitted from person to person, although probably not directly, researchers said."
"Genomic analysis of Mycobacterium abscessus isolates taken from clusters of infected CF patients found almost no sequence differences — in fact, less than is normally found in isolates taken from a single individual — strongly indicating between-patient transmission."
"Whole genome sequencing has revealed frequent transmission of multidrug resistant NTM between patients with cystic fibrosis despite conventional cross-infection measures. Although the exact transmission route is yet to be established, our epidemiological analysis suggests that it could be indirect."
Possibly we differ in the definition of the term "infectious".
[ Although the exact transmission route is yet to be established, our epidemiological analysis suggests that it could be indirect. ]
The analysis suggests that transmission could be indirect rather than direct - which is consistent with Insmed's 10-K -
[ Non-tuberculous mycobacteria, or NTM, are organisms common in soil and water that have been associated with lung disease in select patient groups. NTM have characteristics that are similar to tuberculosis, or TB, but NTM are not contagious. ]
The most important takeaway is that as NTM has never been thought contagious (directly transmissible from person to person) it isn't viewed as having "the potential to pose a serious threat to public health".
The FDA had every right to argue that the QIDP pathway was never intended for a drug targeting a non-contagious disease which is a serious problem for only a small number of people.
I personally believe it to be very significant that the FDA granted QIDP status.
I also consider it significant that one of the key objectives of the federal Interagency Task Force on Antimicrobial Resistance is the more efficient use of antibiotics - given that the Task Force is jointly chaired by the CDC, FDA and NIH (of which the NIAID is part).