Asco – Sirtex spins surrogate hit but no chance for first-line use
How do you push your company’s stock up 14% on the back of a failed trial? By placing huge emphasis on success in a secondary endpoint. Shares in Sirtex Medical rose to A$30.52 today after a presentation at the Asco meeting revealed the extent of a progression-free survival benefit in patients with liver tumours.
The stock is still some way short of where it was before the primary endpoint miss of the Sirflox study was revealed in March. The PFS hit is a surrogate endpoint and as such is unlikely to allow expanded approval, regardless of how much investors buy into these data.
A miss is still a miss
The Sirflox trial was assessing SIR-Spheres, resin beads impregnated with radioactive yttrium-90, as a therapy for metastatic colorectal cancer. The Asco presentation confirmed that the primary endpoint – an improvement in PFS at any site – was a washout, as had previously been reported (Sirtex slips on its beads after trial miss, March 17, 2015).
The SIR-Spheres did cause a significant improvement in PFS among patients with liver tumours, with those given chemotherapy plus the microspheres living a median 7.9 months longer than patients given chemo alone.
Sirflox has shown that while SIR-Spheres can halt the advance of liver metastases from the initial colorectal cancer, they have little to no effect on tumours at any other site.
SIR-Spheres are approved as salvage therapy – the last-ditch defence – and the latest Sirflox data provide little justification for moving them up the treatment cascade. That will only come if the beads can show an improvement in overall survival. Data collection for the mortality endpoint is ongoing, and should become available in 2017.
Two other phase III trials are ongoing in metastatic colorectal cancer with overall survival as their primary endpoints, and will also read out in two years’ time. Given that liver metastases cause the death of the majority of most metastatic colorectal patients, there is just a chance that an overall survival benefit may appear – this, at least, would account for the jump in the share price.
Pending the emergence of an improvement in overall survival, Sirtex will have to grow its sales in the salvage setting. This market is currently 30% penetrated, according to analysts at Goldman Sachs, and may be able to reach 60% by 2020. This would mean an annual growth rate of 17% in the US and 12% in Europe.
Intriguingly, this might be doable. Since the primary endpoint miss in March, sales of the beads have increased nicely, with Sirtex saying that global dose sales in the first 10 months of this financial year were up 22% compared with the same period in fiscal 2014. Sales in March and April 2015 were the two highest monthly figures recorded so far. This could well be another reason for the stock’s increase today.
Expansion into other types of liver metastases will also help. A trial called Sarah is assessing the spheres head-to-head against Nexavar in patients with advanced hepatocellular carcinoma. This will report results next year. Sirtex is also investigating its only product in renal cell carcinoma.
Approval of SIR-Spheres as first-line therapy remains a dream, unless the mortality data show a surprise benefit. But even in the absence of a label expansion, Sirtex’s sales seem to be ticking over acceptably.