CAFA on Sirtex, page-20

Hi Cafa and others, can I put to you a theory I have been mulling over since yesterday afternoon?

As you all know, there are various end points which are being measured for this trial group, and for those end points there is statistical significance (i.e. how sure are we that these results are valid) and clinical significance (i.e. how much improvement is there).

The three end points I would like to focus on are PFS in the liver; PFS (elsewhere) and Overall Survival (OS).

In the SIRFLOX study, PFS (elsewhere) was not obtained. PFS in the liver was demonstrated, and the press release was silent on OS.

As others have noted, for those with mCRC, 90% die of liver cancer. So it would be strange, then, that for patients with mCRC on SIR-Spheres, there is improvement in PFS-liver, but no overall improvement in OS. So strange then as to be almost unbelievable.

So why was this not reported? My theories are:
(1) there was no improvement in OS. So for whatever reason patients may have shown improved PFS in the liver but died anyway - this could be for a number of reasons including side effects of SIR-SPheres themselves. Who knows.
(2) there is improvement in OS but the company declined to release this information. Why would this be the case? Again some theories:
(a) the results were statistically or clinically borderline and they wanted independent verification before releasing to market
(b) they want to release this information as part of the ASCO conference
(c) they need more time to measure OS, and this will be released as part of the FOXFIRE studies (where OS is the primary endpoint)

Now based on other commentary (and I stress I am no expert on this) it was always a very remote chance that SIRFLOX would demonstrate PFS outside the liver, and yet this was the primary endpoint of the trial. So the failure of this primary goal should be no surprise to SRX management. And yet the CEO announced in October that they were confident of a positive outcome, and in the recent HY report they announced a large sum was to be spent this year on explaining the results to market and ramping up production.

So my theory is that this result may still be exactly what they were expecting, and at the ASCO conference they will announce the improvement in OS rates, which will be further supported by the FOXFIRE study outcomes in early 2017. And the SARAH study concluding end-2016 will further demonstrate effectiveness in treating Liver Cancer.

And hence the overall good news story is still intact.

If this turns out to be the case then (a) I will be delighted because I am a shareholder, and (b) it would be a mighty strange way to announce news to the investment markets for a $2.2bn company. But perhaps they have to do it this way so as not to jeopardise what they are allowed to present to ASCO in MAY.

I would really appreciate any constructive criticism or analysis of this theory.

I am also disclosing that I purchased on market yesterday and doubled up today.