According to Janet Woodcock, 63 drugs have been given the “QIDP” designation so far. Our inofficial list has 61 drugs, of which we believe only 57 are still in active clinical development. So we are in fairly close agreement.
That may seem like an impressive record but it is also a bit misleading: There were few new applicants in 2016 and the numbers are plateauing.
But QIDP drugs are just the tip of the iceberg, right? Well, it happens to be a rather small iceberg floating around. Certainly, there are many more antibiotics in development without QIDP status. Some companies choose to wait before applying for QIDP designation or have strategic and financial reasons to postpone the application. Others, also for mostly strategic or publicity reasons, ask for QIDP designation already at the research stage.
Let’s spend some time looking at the larger groupings in the QIDP registry.
#1: ALL THESE AEROSOLS – NOT ONLY FOR CF
FDA makes it easy to garner the QIDP label and the Agency has been most generous to applicants. Too generous, perhaps. QIDP status and benefits were handed out to some drugs that are nothing more than reformulations of old antibiotics. Aerosols lead that list, as every drug class seems to lend itself for aerosol delivery. Of note, they are no longer developed just for lung infection in CF patients but also for non-CF conditions like chronic bronchiectasis, as adjuncts to systemic antibiotics for VAPB prophylaxis and treatment, and for the treatment or suppression of NTM lung disease. These are innovative approaches and makes these drugs more than “TOBI mimetics”.
#2: MORE BL/BLI COMBINATIONS TO COME – BRING ‘EM ON
There is a strong effort underway to develop new BL/BLI combinations. CTAZ plus avibactam was just approved (Avycaz), but avibactam can be combined with other BLs as well. The combination with aztreonam makes a lot of sense, the combination with ceftaroline not so much to this reviewer; both combinations are at an advance stages of development.
Several newer BLI may widen the coverage against MDR pathogens compared to Avycaz. These drugs have small but hopefully important differences in activity against MDR pathogens and Acinetobacter, thus justifying a separate development effort.
From a marketing perspective, the goal may not be to achieve super-activity against all kinds of MDR pathogens but rather ‘mediocrity in excellence’: Companies may prefer to develop a successor to Piperacillin/Tazobactam (Zosyn) and become the new ‘workhorse BL/BLI” rather than cover all classes of beta-lactamases, from A to Z (or D in this case).
Clearly, there are significant hurdles for BL/BLI combos, not just from the scientific perspective. Their commercial potential is hard to predict and the regulatory path to approval may be tougher than it was for Avycaz.
NDM pathogens are not covered by the current crop of BL/BLI inhibitors and it will be important to close this gap.
Could a BLI be developed as a stand-alone inhibitor, to be freely combined with any number of BLs? It sounds intriguing but there are significant regulatory hurdles to this approach. Issues with physicochemical compatibility and mismatched PK argue against free combinations. How about combining Avycaz with another BL? This would create an imbalance in the ratio of BL : BLI; it may still work but should first be explored in relevant preclinical animal models.
#3: TRUE BLUE NCEs – A SMALL GROUP BUT MOST DESERVING
When we look for NCEs in our list of QIDP drugs, we find only precious few systemically active agents. Some may already be on life support, no longer actively pursued. All of them struggle with regulatory guidelines that don’t apply, and with marketing departments that see little commercial value.
Please see more detailed informations in prior blogs of these compounds on our website.