Ann: Regulatory progress for VivaGel BV in the US, page-30

May I remind those who have not been around as long as some of us.

The first Phase 3 trials failed! I was at the AGM where that was discussed. The problem was that, while the symptoms went away and the patients were "cured" the symptoms returned after some weeks.

FDA changed the rules for success and reduced the period by which a cure would be judged and the failed trial became a success.

I recall at the time JF commenting on the recurrence issue and saying it was quite possibly the hygiene or practices of the trial participants which were the problem. Sexual intercourse is an ongoing issue with BV and the presence of sperm tends to cause recurrence. At the time she made the point that the recurrence trial was much more significant. The issue with the recurrence trial is that they did not use Vivagel to cure the participants, they used the leading antibiotic and then Vivagel or a placebo to test recurrence.

My advice would be, given that previous trial results are still admissible, to run a straight Vivagel only trial on participants who test positive for BV. Run the cure regime followed by the prevention regime and test the participants every week. You will have some who do not respond and that is the nature of the condition. But most will (as evidenced by the Phase 1 and 2 trials). You can then use the data from this single purpose trial with the data from the other trials to prove the case (or not).

So much will depend on the parameters agreed for the trial. How long must a participant be symptom free in order to tick the cure box? Can we eliminate participants who admit unprotected intercourse (a known risk factor) during the trial?