The QIDP designation was introduced in 2012 to incentivize drug development in antiinfectives. QIDP came with several attractive features, such as prolongation of patent life, FDA expedited review and more. In addition, FDA made it quite easy to garner the label. As you can see, there is really no downside to obtaining QIDP status. Therefore, it would seem logical that antibiotics in development with any degree of differentiation would clamber for recognition as QIDP drugs.
There may be good reasons to request QIDP at a particular time in development: early on for external validation of a project, or at a later stage in order to attract funding or to ‘dress up the bride’ before that all-important outlicensing effort gets underway. It is hard to think of a situation in which a company would want to forgo applying for QIDP status altogether unless the drug was moribund or about to become shelved.
Right after its introduction, we saw a flurry of QIDP announcements reflecting pent-up demand from an existing pipeline. After this initial wave, one would expect things to settle down to a steady state as new applicants backfilled the pipeline. Sadly, 2016 is shaping up to become a particularly dry harvest year (Table 1):
After excluding antifungals and topical, inhalational, and non-absorbed compounds, we are left with the following tally of systemically active antibacterial drugs (Table 2):
We are now in the second year of single digit QIDP nominations, not a pretty picture, for sure. Those 5 new antibiotics that garnered QIDP status in 2016 are highlighted below (Table 3):
If one considers QIDP as a pull incentive, it has failed us: There is only a very small number of preclinical and early compounds which can be swept off the roster rather quickly. In this fragile field, we found only 2 candidate drugs with a truly novel MoA: TXA-709, a drug directed against the bacterial FtsZ ring protein, a critical and validated cell division target, and GSK-2140944, a topoisomerase II inhibitor that is different from the established fluoroquinolone class. Btw, the Entasis compound ETX-0914 falls into the same category.
We are not sure whether MCB-3837, a quinolone linked to an oxazolidinone, should be listed as a new antibiotic class. Confusingly, this combination is being referred to as ‘oxaquin’ which happens to be a trade name for moxifloxacin in some parts of the world.
Noticeably absent from this year’s list are QIDP awards for some other new MoA drugs which should have matured by now. We are thinking of the LpxC, FabI, PDF and tRNA synthase inhibitors, just to mention a few. Some of these have been in clinical development for a long time already; the Chiron / Novartis LpxC inhibitor is no longer in development but Achaogen’s ACH-975, a perpetually preclinical LpxC inhibitor, is still on their pipeline chart. GSK really had bad luck with GSK-2251052, a tRNA synthase inhibitor from Anacor but Crestone continues to work on a compound for topical use. The Affinium, now Debiopharm FabI, has been leading a life in the shadows for a very long time; it is time for all these projects to out themselves.
As it stands, the QIDP engine is barely cranking and certainly not developing much torque. Nevertheless, in the spirit of Thanksgiving, let’s stay positive: We still have antibiotics that work. We will need to really start worrying about the pipeline once veterinarians stop using antibiotics in livestock because growth promotion no longer works.