As part of the effort to manufacture GMP grade PBT1 (clioquinol) for clinical trials, Prana found unacceptably high levels of a di-iodo (toxic) form of PBT1. After further investigation, the company now believes it is possible that the di-iodo impurity that occurs during PBT1 synthesis could be responsible for an increased risk of side-effects and mutagenicity.
While Prana has considered methods to reduce the levels of the di-iodo impurity, the company said it has come to the conclusion that attempts to reduce the impurity to safe levels are not likely to be successful in a timely manner and that further development of PBT1 is not warranted.
The company does have a backup compound for Alzheimer’s disease, PBT2, which is currently in phase I clinical testing in Utrecht, the Netherlands. PBT2 has a structure that does not contain iodine and is therefore not capable of forming the di-iodo impurity that has been associated with mutagenicity.
As a result of these events, Prana is conducting a strategic review of its development programs.