Sirt result, page-38

Wilson HTM note

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0	Sirtex Medical (SRX)
1	SARAH abstract and EASL/ILC presentation – first thoughts on the primary endpoint miss
2	Announcement highlights
3	· The SARAH clinical trial results were presented at the EASL/ILC conference over the weekend. As a reminder, this Phase III, investigator-led clinical trial sought to test Sirtex Medical’s SIR-Spheres product head to head against the chemotherapy drug sorafenib, in treating patients with advanced, inoperable liver cancer (HCC). SARAH was the first prospective, randomised clinical trial to assess the efficacy of SIR-Spheres in this setting. · The trial did not achieve its primary endpoint, with the investigators concluding that “overall survival did not differ between sorafenib and SIRT (SIR-Spheres)”. There was no statistically significant difference on the primary endpoint of overall survival (OS). Two secondary endpoints did yield significant results: SIR-Sphere treatment was associated with a 27% reduction in the risk of tumour progression in the liver and scored a higher tumour response rate. The reported number of treatment-related adverse events was also lower for SIR-Spheres, suggesting better safety. Table 1: SARAH abstract data summary Source: EASL/ILC · We expect that Sirtex will convene a conference call to present more detail from SARAH early tomorrow morning.
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5	Wilsons’ view
6	Initial analysis
7	· The key question now is whether or not a non-inferiority claim might still be established in HCC. The most hopeful interpretation of the “negative” SARAH result is that there was no true benefit to detect – that the treatments may actually be equivalent on overall survival. Such a claim is desirable, because if SIR-Spheres is proven to be equally effective, its other potential advantages over sorafenib become more important. The SARAH abstract suggests better safety; and SIR-Spheres is also likely to be more cost effective, in our view. From here, the non-inferiority claim depends on the outcome of the SIRveNIB trial (abstract available on 17 May) and the pre-specified, pooled analysis of those two trials – a piece of work called VESPRO – reporting results in the second half of this year. VESPRO will take individual patient data from both SARAH and SIRveNIB and has prospectively defined how non-inferiority will be assessed in a scientifically valid way. · The progression benefit in the liver was expected. To our knowledge, this is the first time that SIR-Spheres’ efficacy in controlling HCC tumours in the liver has been proven in a prospective randomised controlled trial, with statistical significance. · Properly understanding the primary endpoint miss. We’ll be particularly interested in seeing the “per protocol” analysis of overall survival, which will only include patients who completed treatments as per the trial guidelines – a different analysis to the “intent to treat” analysis which is provided in the abstract. SARAH also stratified patients to delineate responses in important sub-groups of HCC patients: on the basis of their health status (ECOG score), their prior chemoembolization treatment history and the presence/absence of vascular involvement. Plenty of data to wade through tomorrow.
8	Earnings implications
9	· We will review our forecasts following the Sirtex conference call but at this stage it is unlikely that we will change our numbers. The current forecasts do not contemplate any change in SIR-Spheres’ status as a treatment for HCC. A valid non-inferiority finding would be of earnings significance, in our view, but we may still be several months away from having that outcome confirmed.
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11	Investment view
12	· Our last published target price was $15.50 per share, which is based on traditional “salvage therapy” demand only. No upside is recognised from the series of Phase III clinical trials reporting between now and June. HOLD rating maintained.
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