In its announcement today Sirtex Medical said it was pleased to report the preliminary results of its phase III Sirflox study, but frankly that seems unlikely. The trial failed, and Sirtex’s dreams of having a first-line therapy for metastatic colorectal cancer are dead. The company’s shares fell 55% to A$17.53, wiping more than A$1.2bn ($1bn) from its market cap.
Investors had anticipated a win for the Sirflox trial, with Sirtex’s stock soaring 142% throughout 2014 largely on this expectation. Sirtex’s radioactive beads, called SIR-Spheres, are currently used as salvage treatment in patients who progress on chemotherapy, and unless its other phase III trials in first-line use somehow register a win this is where they will stay.
Sirflox enrolled 518 patients with inoperable metastatic colorectal cancer and pitted SIR-Spheres – resin microspheres containing radioactive yttrium-90 – in combination with folfox chemotherapy against the chemo alone.
There was no statistically significant improvement in overall progression-free survival – a measure that tracked tumour growth or development anywhere in the body – in the treatment arm over the control. A secondary endpoint was met, with beads plus chemo showing a significant improvement in PFS in liver tumours.
The microbeads are infused into the liver and are designed to lodge preferentially in the microvasculature surrounding the tumour, killing it while sparing healthy tissue. According to the company, liver tumours are often the main site of disease in patients with metastatic colorectal cancer, and up to 90% of these patients die of liver failure as a result.
Full data from the trial will be released at this year’s Asco meeting.
The company has two other phase III studies in first-line metastatic colorectal cancer: the UK-based Foxfire and Foxfire Global. Like Sirflox, both are testing the beads plus folfox chemo vs chemo alone, but unlike Sirflox their primary endpoints are overall survival. Results are expected in the first half of 2017, but if the therapy cannot show a PFS advantage it is unlikely to meet the tougher standard in the Foxfire trials.
The only other radioactive microbead therapy in metastatic colorectal cancer is Therasphere, obtained by BTG when it bought the Targeted Therapies division of Nordion for $200m nearly two years ago (BTG’s acquisition flurry underlines medtech interest, May 23, 2013). However, perhaps wisely, Therasphere is in a phase III trial in patients who have failed on chemotherapy, rather than the first-line setting.
Anticipation of the Sirflox data was not the only factor in Sirtex’s share ramp last year: to do the company justice, sales and profits have grown, in percentage terms, even more.
First-half revenues in fiscal 2015 jumped 37% to AUS$81m on rising demand for SIR-Speres, the company's only marketed product. Profit was up 58% year-on-year, at AUS$18m. The company was planning to spend AUS$8m or so on marketing in the second half of financial 2015 in anticipation of approval and launch of a first-line therapy. At least it can put this cash back in its wallet.
The company may now turn to its trials in other cancers; Sirtex is testing SIR-Spheres in hepatocellular carcinoma and renal cell carcinoma, and academic researchers are trying the technology in breast cancer and melanoma.
But the blow has fallen, and Sirtex must get used to being half the size it once was.
|Phase III trials of SIR-Spheres in metastatic colorectal cancer|
|Name||Number of patients||Endpoint||Results||Trial ID|
|Foxfire||360||Survival||Expected H1 2017||-|
|Foxfire Global||200||Survival||Expected H1 2017||NCT01721954|