Compared with the behemoths of chemo and radiotherapy, anticancer embolisation technologies are small fry, used as salvage therapy in patients who otherwise have little hope. But this could be changing. The Australian group Sirtex Medical (OTCPK:SXMDF) has started a raft of trials with the ambitious goal of moving its SIR-Spheres product from last place in the treatment sequence to first.
Sirtex is already outpacing Nordion (NYSE:NDZ), the only company marketing a rival technology, and if the trials succeed it will lengthen its lead. But Sirtex’s real challenge will be convincing oncologists to abandon long-trusted treatments in favor of something newer and stranger.
SIR-Spheres are resin microspheres around 30 microns in diameter, containing the radioisotope yttrium-90. In a minimally invasive procedure, millions of SIR-Spheres are infused via a catheter into the liver where they emit a dose of radiation that Sirtex says is 40 times higher than conventional radiotherapy.
They are approved in the U.S. for the treatment of unresectable metastatic liver tumors from primary colorectal cancer, in combination with intra-hepatic artery chemotherapy of floxuridine. In Europe, however, the therapy is CE marked for the broader indication of any non-operable liver cancer.
Around 100,000 patients each year become eligible for SIR-Sphere treatment of their primary and secondary liver cancer, according to analysts at Nomura Equity Research, and Sirtex has so far only reached 6.1% of this market. Moving the treatment from last place to first-line could increase the patient population to 600,000 worldwide, the analysts say. And Sirtex has a well-defined plan for how to go about it.
Last week, the company completed enrollment of 518 patients who have colorectal cancer with liver metastases into the Sirflox trial. This will test the spheres as first-line therapy in combination with the Folfox chemotherapy regimen, compared with Folfox alone. Primary results from the study will be collected in around a year, and Sirtex says it will make them available in late 2014. Foxfire, a near-identical 490-patient trial, is also under way and should report in 2016, according to Edison analysts.
Also reporting in 2016 is Sarah, a head-to-head trial of SIR-Spheres versus Bayer’s Nexavar as a first-line treatment for advanced hepatocellular carcinoma. The trial is enrolling 400 patients with inoperable primary liver cancer.
Edison analysts point out that earlier studies in both indications have been positive. A trial in 21 patients with liver metastases from colorectal cancer had median overall survival of 29.4 months with SIR-Spheres plus leucovorin and fluorouracil – two of the components of Folfox – compared with 12.8 months for the chemotherapy alone. In hepatocellular carcinoma, a 35-patient trial reported progression-free survival of 16 months, double that seen in the control group.
Nomura analysts are bullish, stating boldly: “We believe these larger trials are likely to succeed.” But Edison analysts are concerned about the potential rate of uptake in the first-line setting.
Craig Collie, an analyst from Macquarie Equities Research, has addressed this very question, surveying radiation oncologists for their opinions of the technology. He found that specialists on the radioembolisation market were positive, with 67% believing that radioembolisation will play a larger role in therapy the future. Only 29% currently offer the treatment, meaning Sirtex has room to expand, and most only use the treatment as a third-line therapeutic.
If the ongoing trials can persuade the authorities and oncologists that SIR-Spheres ought to be used first-line, Sirtex will be able to vastly increase its market, and will also be better able to win over hitherto unconvinced oncologists.
|Ongoing phase III trials of SIR-Spheres|
|Name||Details||Indication||No of patients||Trial ID|
|Sirflox||Folfox plus SIR-Spheres vs Folfox alone||Liver metastases from primary colorectal cancer||518||NCT00724503|
|Foxfire||Folfox plus SIR-Spheres vs Folfox alone||Liver metastases from primary colorectal cancer||490||-|
|Sarah||SIR-Spheres vs Nexavar (sorafenib)||Advanced hepatocellular carcinoma||400||NCT01482442|