The Business of Pharmaceuticals

US-based Bayer Healthcare Pharmaceuticals, as its executives were quick to point out, has now received three new approvals for cancer indications in the last eight months.

Bayer and Algeta's Xofigo employs a radioactive isotope to target bone metastases.

Two of those approvals were for Stivarga, for metastatic colorectal cancer at the end of last September, and for gastrointestinal stromal tumor, or GIST, in February. On Wednesday, FDA approved Xofigo (radium Ra 223 dichloride), an alpha-emitting radioactive drug indicated for symptomatic late-stage metastatic castration-resistant prostate cancer.

Like Stivarga, Xofigo was granted accelerated approval, and both drugs received an FDA thumbs up prior to their respective PDUFA dates. Xofigo is “the first and only alpha-emitting pharmaceutical available in the market,” says Shannon Campbell, VP and general manager, oncology, at Bayer Healthcare Pharmaceuticals. Combined with the standard of care, Xofigo extends overall survival in men with advanced prostate cancer, who also have bone metastases, by slightly less than three months, as demonstrated in the phase 3 ALSYMPCA trial, which evaluated 809 such patients.

The science behind Xofigo, which was discovered by Algeta ASA, a Norwegian biotech, and in-licensed by Bayer (the companies will co-promote the drug in the US), sounds like science fiction, at least to the layman. Radium 223 emits alpha particles that mimic calcium, and target bone; they don’t affect the surrounding healthy tissue, explains Pam Cyrus, VP, head of medical affairs, at Bayer Healthcare Pharmaceuticals. The alpha particles “are less than 100 micrometers, which is less than the size of 10 cells,” which makes for a very localized treatment. The course of therapy is six intravenous injections, one every four weeks, or once a month for six months. Hospitals or clinics that want to administer the drug will need to make sure their radiopharmaceutical licenses are up to date, an administrative step and a regulatory requirement for administering a radioactive drug, says Campbell.

Like FDA, physicians tend to like novel, brand new mechanisms of action, so long as they’re safe and efficacious. Campbell said Bayer’s engagement with the healthcare community so far has uncovered “a set of assumptions about radiopharmaceuticals, which are really tied to the older products in the market, the beta emitters, which are very different” from Xofigo. But “when you move into the mechanism, and also the magnitude of benefit…that gets their attention pretty quickly.”

Prostate cancer, given the devastating unmet need the disease represents, has been a hot development area for many companies in recent years. FDA has approved several products for advanced prostate cancer in the last few years, including J&J’s Zytiga and the Medivation/Astellas drug Xtandi, but Campbell says she doesn’t view these products as direct competitors. “The challenge in the prostate cancer market right now is…determining the right sequence for the products, and what are the right types of patients that would receive more hormonal directed therapy versus something else,” she says. Men experiencing the first symptoms related to bone metastases, “whether it’s pain, discomfort, taking narcotics…that is really the sweet spot for Xofigo, and that’s what differentiates it from everything else.”

Xofigo will hit shelves one to two weeks from now, and Bayer will continue to explore other possible indications for the drug, specifically in tumor types with a “heavy, bone-dominant component,” says Campbell. Bayer has global commercial responsibilities for Xofigo, but Algeta will co-promote the product in the US. A combined 140 to 150 “boots on the ground” will support the product, a team comprised of traditional sales reps, radiation therapy specialists, MSLS and other administrative support personnel. Xofigo will be “pretty well covered by most commercial plans, and Medicare,” says Campbell. “It may take a little bit of time to get put on some formularies, but during that process we have a very robust Xofigo access services program in place, to help healthcare providers and patients.” Bayer declined to name the advertising agencies working on the launch or campaign.

At ASCO, Bayer will present phase 3 data on Nexavar, the cancer drug it co-markets with Onyx, for locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer, and the company has also another phase 3 trial for Stivarga, in advanced liver cancer.