Precious Mettle - Pharmaceutical Executive


Precious Mettle

Pharmaceutical Executive

Product to Portfolio

Multiple myeloma is currently a $4 billion market, and is expected to grow to more than $7 billion by 2015. Over 215,000 people worldwide are currently living with multiple myeloma, and roughly 86,000 are diagnosed each year. The deal with Proteolix, including an oral proteasome inhibitor (ONX 0912), and an immunoproteasome inhibitor (ONX 0914), was structured favorably for Onyx, says Liang, allowing the company to provide a "modest upfront"— $276 million—"and then pay [up to $535 million] on the success of the back end, as the compound receives regulatory approval." An additional development milestone payment of $40 million was made in 2010, bringing the total cost of the deal to $851 million, assuming US and European approval on carfilzomib. Unlike Nexavar, whose profits and development costs Onyx splits 50/50 with Bayer, (with the exception of Japan, where Onyx gets a royalty), Onyx owns worldwide rights to carfilzomib. Liang cites that strategy as the right one for the new Onyx. He cites Celgene and Alexion as two examples of companies "that have done well, at least from a market valuation perspective," by holding on to US as well as worldwide rights.

With Nexavar (sorafenib) bringing in close to $1 billion dollars annually in global revenues—sales were up in 2010 by 11 percent, to $934 million—Onyx can afford to put substantial investment into developing its pipeline. Pfizer's investigational drug axitinib could take a bite out of Nexavar's profits if it's approved—a Phase III head-to-head trial showed axitinib besting sorafenib in terms of extending progression-free survival in kidney cancer patients by two months—but Nexavar is also in the clinic for additional indications, including thyroid, breast, ovarian, and colorectal cancers. The drug has produced disappointing results as a treatment for non-small-cell lung cancer and melanoma, but Onyx anticipates up to five new filings for Nexavar over the next two to three years, the company says. Additionally, gains have been made on the global front, thanks to Bayer's network strength and reimbursement finesse. Bayer won reimbursement coverage for Nexavar's liver cancer indication in South Korea late in 2010, and hopes Taiwan will follow suit this year.

Bayer and Onyx have also targeted non-oncology specialists who see patients with liver cancer, including hepatologists and gastroenterologists. These specialists have been eager to play a role in treatment, but had nothing other than hospice care at their disposal, says Coles. "It became clear that we were capturing patients once they got to an oncologist, which is our traditional call audience, but we wanted to try to identify patients earlier, at the moment of diagnosis," he says. Oncologists treat most cancer patients, but with liver cancer, it's a cross-functional team of physicians, says Coles.

The recognition that non-oncologists are identifying and diagnosing liver cancer, and that these non-oncologists are willing to write Nexavar prescriptions, was an insight Coles attributes to his background in marketing. "The hepatologist audience has been incredibly receptive to the educational messaging around Nexavar, and the role that Nexavar can play," says Coles. Outreach to this audience—which also includes surgeons and interventional radiologists—includes a mix of direct detailing, educational efforts and symposia, and has doubled Nexavar prescription volumes within that audience over the last three years, says Coles.

Expanding the Portfolio

Right now, Onyx's priority is to get the carfilzomib NDA filed, but the company is also looking down the road, at portfolio development and opportunities in markets beyond the US. While Coles is keen on keeping his proteasome inhibitors close to the vest and building Onyx's commercialization capabilities, he recognizes that the scale of investment required in certain geographies is a hurdle for a company with just 300 employees. "It's the Asia-Pacific markets that present an interesting conundrum ... We think Big Pharma's partnership help in those markets still makes a lot of sense," says Coles.

To address the problem of commercialization in Japan, Onyx signed an exclusive agreement with Osaka-based Ono Pharmaceutical Co. last September, to develop and commercialize carfilzomib and ONX 0912, an oral proteasome inhibitor currently in Phase I. The deal came with an upfront payment of roughly $59 million, and the potential for another $280 million based on "development and sales-based payments related to the compounds." Onyx is also entitled to "royalty payments in double-digit percentages on net sales in Japan, commensurate with a late-stage asset," according to a statement on the deal. "This was the best way into the Japan market for us," says Coles. We have a similar point of view for Latin America and Asia-Pacific." The company is actively looking for partners in those territories.

From a business perspective, the US cancer space beyond Nexavar is "a great entry point for a company our size, because it's all scalable. You can have a modest number of field-based personnel and they can reach the target audience very effectively, with messages that the [specialist audience] really wants to hear," says Coles. Onyx is also "analyzing all of the ways in which we can get into Europe," which includes partnering for a limited time, while building infrastructure, or launching in the top five territories as a single company, "but the goal is to retain significant downstream value for the compound in Europe," says Coles.

Adding to carfilzomib, ONX 0912 gives Onyx "the opportunity to have a franchise in multiple myeloma," says Coles. ONX 0912 will enter Phase II later this year, and despite this early stage of development, Coles says the drug is "active and bio-available," and the degree of proteasome inhibition in patients with solid tumors "is comparable to carfilzomib." If proteasome inhibition is a proxy for efficacy, and Coles thinks it is, "we could have a highly efficacious oral drug on our hands," he says.

In the run-up to carfilzomib's expected NDA submission, Onyx decided not to exercise an option on two janus kinase (JAK) inhibitors from S*Bio, a Singapore-based biotech. That deal was first announced in January 2009, and expanded in 2010 (Onyx paid $25 million upfront, and another $20 million when the deal was expanded in May 2010), but was cancelled in May of this year. The original deal was worth up to $550 million total, but Onyx decided to put its energies and resources into carfilzomib, the company said. Despite numerous ongoing clinical activities, with proteasome inhibitors (Onyx's immunoproteasome inhibitor, ONX 0914, which would potentially target autoimmune diseases like rheumatoid arthritis, lupus, and psoriasis, is a first-in-class therapy currently in the preclinical phase), and development costs in support of additional Nexavar indications, the company is fairly well-heeled. At the end of 2010, the company had $578 million in cash, a respectable figure, according to Laing. Coles says Onyx will "keep an eye out for the next great opportunity in the oncology space."


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