Axitinib Poised To Join Pfizer's RCC Drug Portfolio In 2012

Pfizer's second generation VEGF inhibitor axitinib for advanced renal cell carcinoma has been granted a standard, 10-month review by FDA.

Pfizer Inc.'s second-generation VEGF inhibitor axitinib has been granted a standard, 10-month review by FDA for the second-line treatment of advanced renal cell carcinoma, positioning it for a potential launch in the early half of 2012. If approved, axitinib would be Pfizer's third drug for the treatment of RCC, joining the VEGF inhibitor and market leader Sutent (sunitinib) and mTOR inhibitor Torisel (temsirolimus).

Pfizer announced on June 28 that FDA has accepted the axitinib filing. Earlier in June, European regulators accepted an axitinib application as well.

RCC is one of the most crowded areas of oncology therapy, with six targeted agents already on the market for what is a relatively small patient population. But Pfizer - and others who are developing drugs in the space - insist room exists for new therapies.

Pfizer Senior VP of Clinical Development and Medical Affairs Mace Rothenberg addressed the question during a presentation of the axitinib pivotal data at the American Society of Oncology annual meeting June 6. "Do we need another drug in this disease?" he asked. "When you look and see that 13,000 Americans will die from renal cancer, there is your answer. As good as we are, we are not as good as we can be so the answer is clearly yes, we do need additional drugs."

Axitinib would, in the near-term, be a second line treatment option for patients with advanced disease. The pivotal study used to support the filing, the Phase III AXIS 1032 trial, compared axitinib to Bayer AG/Onyx Pharmaceuticals Inc.'s Nexavar (sorafenib) in patients who had progressed on earlier treatment, including Sutent and cytokines. Pfizer is running a second Phase III study that includes both treatment-naive and previously treated patients, which could extend the drug's use into the first-line.

Axitinib Demonstrates Improvements In PFS

Results of the AXIS 1032 study showed axitinib extended progression-free survival by a median of three months to 6.7 months, compared with Nexavar. The trial enrolled 723 patients with clear-cell advanced RCC who had been treated with prior therapy including Sutent (54%), cytokines (35%), Roche Holding AG's Avastin (8%) or Torisel (3%). PFS was statistically significantly longer in axitinib-treated patients in both the prior cytokine-treated subgroup (12.1 months versus 6.5 months) and those treated with Sutent (4.8 months versus 3.4 months).

Approval of axitinib will put more pressure on Nexavar. "Axitinib [is] likely to make a bad situation worse," Robert W. Baird analyst Christopher Raymond said in a June 7 research note on Onyx. "Nexavar's U.S. second-line RCC patient share has suffered greatly (2010 share is 12% down from 40% early 2008) at the hands of Afinitor and Torisel, growing revenue - we believe - solely on aggressive price increases. A 2012 axitinib approval is likely to only accelerate this trend."

Sales of Nexavar, which is also approved for liver cancer, were €705 million ($1.01 billion) in 2010. Sales of Sutent, which is approved for gastrointestinal stromal tumors and just received FDA clearance for pancreatic neuroendocrine tumors in May, were $1.07 billion in 2010.

In addition to Nexavar and Sutent, which were approved back-to-back in December 2005 and January 2006, respectively, several other drugs have since been approved for kidney cancer, including Torisel in 2007, and GlaxoSmithKline PLC's Votrient (pazopanib), Novartis AG's Afinitor (everolimus) and Roche's Avastin (bevacizumab) in 2009 (Also see "RCC Market Snapshot: In A Crowded Field, What's Next?" - Pink Sheet, 5 Apr, 2010.).

Axitinib, like Sutent, Nexavar, Votrient and Avastin, is a VEGF inhibitor, but it is highly selective, according to Pfizer, targeting only VEGF-1, 2 and 3 receptors, key targets in renal cell carcinoma. Afinitor and Torisel inhibit mammalian target of rapamycin, mTOR, and have been shown to have benefits in patients with certain high-risk characteristics.

Another up and coming drug is Aveo Pharmaceuticals Inc./Astellas Pharma Inc.'s VEGF inhibitor tivozanib, which could soon enter the market. The drug is in the final stages of a Phase III trial, TIVO-1, comparing it to Nexavar for the first-line treatment of RCC. Pending positive data, expected in the fourth quarter "at the earliest," the company plans to file in 2012. Aveo signed a lucrative licensing deal with Astellas for shared rights to the drug in February, getting $125 million upfront and potential milestones of $1.3 billion (Also see "Astellas Pays $125MM Up-Front To Share Rights To AVEO's Tivozanib" - Pink Sheet, 16 Feb, 2011.).

-Jessica Merrill ([email protected])