Well AB I’m going to have a good sleep tonight and see whether I...

Well AB I’m going to have a good sleep tonight and see whether I have a nice dream about SPL or a nightmare.

The nice dream might go something like this.

The FDA is a Federal agency that has got kicked around by the government wanting it to hurry up with its decision making. But it is staffed by highly competent professional staff who do their work thoroughly and to very high standards. And so when silly time pressures are put on them they find a way around this.

CRLs are one way around having to meet internal time pressures. The FDA issues a CRL citing a couple of minor issues that are easily addressed. This stops the time clock and gives the reviewers more time to consider the application. The company comes back in a month or two with the issues fixed, the reviewers don’t find any serious problems in the application in the meantime and so it is approved.

In this scenario vivagel is approved without SPL having to anything much at all.

The nightmare scenario is there is no fix possible.

Use the European study to show the problem. The rBV rate was placebo 22.6% and vivagel 15.7%. The “doing nothing” rBV rate was estimated at 65%.

SPL claim the patient benefit from vivagel was 65%-15.7%= 49.3%. But this isn’t true. The patient benefit from being in the trial was 42.4% (doing nothing – placebo). An additional 6.9% benefit was gained from vivagel.

So simply being in the trial was 6 times more powerful than vivagel in reducing rBV. This assumes that the placebo was in fact inert (reasonable for a bacterial infection) and that the placebo response (being in the trial) was the same across groups; a simple additive model.

So in this scenario the problem can’t be fixed because you don’t exactly know why women in the trial had such a good placebo response. And even if you did know it is most likely either not ethical / practical to remove this “active” out of the placebo.

When the FDA has said that they accept vivagel efficacy from the P3 trials I take this to mean that they consider the trials were well controlled and the treatment difference found between placebo and vivagel was true. So SPL can run as many of these trials as they like; but they will just produce the same answer. And that answer (about 7% benefit) relative to the trial benefit of 42% is not clinically significant.

In response to your question though - I would only ever consider investing in SPL if they were transparent. In this respect I believe (my opinion) that they have received a CRL but not acknowledged this to investors and this alone makes them untouchable.

If they have received a CRL they would then also need to provide more than two words (“confirmatory data” about what the FDA has said the problem is as well as details about how the FDA have suggested in that CRL how the problems can be fixed.

I would use a simple benchmark. The median length of a CRL is 1151 words (non-standardised language). The median length of the corresponding company announcement to that CRL is only 193 words (of non-guff). Quite a bit of “informational drop-off” – but not down to 2 words.

https://www.bloomberg.com/news/articles/2018-01-18/fda-crl-letters-more-transparency-is-better

https://www.bmj.com/content/350/bmj.h2758

Let me ask you AB – would you buy a car from a used car salesman if he wouldn’t let you look under the hood? Not me and particularly not if I was a mechanic who had a little bit of an idea of what to look for.