Innovation Pharmaceuticals Inc (IPIX)

[BonelessCat]

Repost with corrections: Trial failure

Inability to meet any primary outcome:
Phase 1 and 2 trials one of the primary outcomes is always safety. Failure to meet agreed upon safety measures always leads to trial failure with a possibility of redesign and repeat the level of trial once safety issues are addressed. A good example of this was Brilacidin ABSSSI Phase 2a where there were two safety issues cited. The doses were lowered and the escalation trial redesigned as a Phase 2b. The FDA approved the 2b as having addressed safety concerns.

Phase 3 trials generally fail with efficacy as a primary outcome. A drug can fail as noninferior to a standard of care, that is it is less effective than the current standard. It can also fail as being as effective but has more risk of side effects with little or no benefit over the current standard. Or, of course, it can fail if the final data has little or no improvement over a placebo.

However, one should note that "safety" is rather a squirrelly notion, one that shifts with the mortality of the disease or condition and the toxicity and reactions to the drug when administered. Cancer drugs might have rare side effects that can lead to death, yet may still be considered acceptable against the mortality rate of a particular cancer with few or no treatment options. An antibiotic, on the other hand, with plenty of options, might fail due to something as simple as elevated blood pressure and rare cases of kidney damage.

It's seldom that a trial fails when secondary outcomes are not met, except when they are safety outcomes for late stage trials. Vaccines often fail for this reason. A dengue vaccine, a few years back, failed after administration of 25000 doses in a Phase 3 trial. Seems some of the vials had attenuated dengue strains that reverted to wild type. I believe there were 5 doses administered that gave subjects dengue who subsequently died.