In October of this year, the FDA released a report entitled, “Driving Biomedical Innovation: Initiatives to Improve Products for Patients.” There are a number of interesting aspects of this report. The first is that the word antibiotic is only mentioned once – in a paragraph talking about clinical trails for targeted therapies. But the study of antibiotics in clinical trials has at best only rare and controversial attempts to do just that. One was the use of emergency use programs to approve the use of linezolid (Zyvox) and quinupristin-dalfopristin (Synercid) for the treatment if serious infections caused by vancomycin-resistant Enterococcus feacium. One major advantage of these emergency use programs is that patients enrolled were documented to have or were very strongly suspected of having a resistan enterococcal infection at the time of enrollment. But given the non-comparative nature of the trials and the bias introduced by the emergency use approach, the FDA has indicated that they would never approve another antibiotic in this way again. But if not, then how?
The following excerpt is taken directly from the FDA report:
The early discovery of a potential
breakthrough therapy raises ethical and
trial design issues. It is important to gain
confidence that the effects seen in the early
trials are real, and to understand the safety
risks of the new drug. On the other hand,
from an ethical standpoint, it is important to
make sure that people with serious diseases
are getting the best possible therapy. In these
situations, the clinical trials for the drug’s
development must be compressed and the
evidence about its effects gathered in the most
efficient manner possible; however, there is
not a good understanding in the biomedical
community about how to accomplish this.
Additionally, there are questions surrounding
the use of an expedited drug pathway, such as:
• Can FDA, drug developers, and
investigators agree on a threshold to
determine when a treatment poses
“exceptional promise” and should thus
be treated in an expedited fashion?
• Can seamless drug development programs
be created to utilize natural history
data or adaptive trial design concepts to
compress drug development time?
• What are the ethical issues involved in
identifying a promising intervention?
How should the needs of all patients with
the disease be balanced against the need
for better therapy for an individual?
• Can surrogate outcome measures that
could be used for accelerated approval
be rapidly identified?
• Can we arrive at a consensus view of
the goal of monitoring commitments
companies will make once a product is
on the market after such a development
program, such as scientific expectations
and timelines?
These are all great questions. I can’t wait to hear the answers!
In other sections of the report, the FDA discusses their intent to better communicate with small business. While I am excited about this initiative since the FDA indicates that it wants to improve their understanding of the challenges faced by small businesses, I wonder whether the FDA will actually be able to provide feasible pathways forward for small businesses developing antibiotics. As it stands now, for example, there is almost no way a small biotech can take on the expense of a registrational trial for antibiotics. Only truly innovative trial designs will change this. But given the departure of large pharmaceutical companies and their deep pockets from the antibiotic R&D area, and given the current dismal situation for private funding, we desperately need these biotech to be able to proceed on their own. A feasible and less expensive pathway for FDA approval would go a long way to bring new therapies, including new antibiotics, to the patients that so desperately need them.
So – if the FDA is serious about their small business initiative and if antibiotic development is included within this rubric – I hereby volunteer my services. Of course, the problem is that they might not like what they hear.
No matter how one feels about the FDA, their report on initiatives in biomedical innovation is an important one. I think it does indicate a sincere desire to move forward. But, as always, the devil is in the details.
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