Bayer HealthCare Pharmaceuticals wasted no time moving the oral multikinase inhibitor Stivarga (regorafenib) to market in metastatic colorectal cancer (mCRC) following FDA approval Thursday morning.
Although the move came a full month ahead of the drug's PDUFA date of Oct. 27, the company already had product in its distribution channel for shipment to customers beginning Friday morning, according to Shannon Campbell, vice president and general manager for oncology at Bayer HealthCare, of Wayne, N.J., a unit of Germany's Bayer AG.
"Stivarga has been on a very accelerated path," Campbell told BioWorld Today. "The development program moved very quickly, and the regulatory approval came faster than was anticipated."
The speedy launch is "in keeping with that theme of bringing this important new treatment to patients as quickly as possible," Campbell added. "There should be no delay in making [Stivarga] available."
Bayer has been working to educate physicians about the compound for several months in response to interest raised through its expanded access program.
Bayer priced Stivarga at $9,350 for a 28-day cycle a price Campbell said compares favorably with existing oral colorectal cancer therapies. Because mCRC represents an area of high unmet medical need, and based on interactions with the payer community, the company expects most health plans and Medicare to cover the drug. Until Stivarga hits formularies, Bayer will provide reimbursement support and patient access through its REACH program, according to Campbell.
Under an October 2011 agreement with Onyx Pharmaceuticals Inc., of South San Francisco, regorafenib is recognized as a Bayer compound, with Bayer having decision-making authority for its global development and commercialization. That agreement ended a long-running legal dispute between Onyx and Bayer over the compound's development. (See BioWorld Today, Oct. 13, 2011.)
Onyx didn't walk away empty handed, however, gaining 20 percent of worldwide net sales of regorafenib in oncology, as well as the right to co-promote the drug in the U.S. and to provide related medical science liaisons under a fee-for-service arrangement.
In addition, Onyx was released from any obligation to pay past or future development and commercialization costs for the compound.
Onyx exercised its co-promotion rights and will begin jointly co-marketing the compound in the U.S., effective immediately, according to Lori Melançon, a company spokeswoman.
"We're using the existing Nexavar sales force that we have already in place with Bayer and have enhanced it modestly with a few more people to cover the appropriate territories," Melançon told BioWorld Today. "Many of the physicians who treat liver cancer and kidney cancer also treat colorectal cancer, so we'll be targeting many of the same physicians."
Onyx's Nexavar (sorafenib), also partnered with Bayer, received the FDA's blessing in advanced renal-cell carcinoma in 2005 and, two years later, in unresectable hepatocellular carcinoma. (See BioWorld Today, Dec. 21 , 2005, and Nov. 20, 2007.)
mCRC Just the Beginning for Stivarga
Stivarga's safety and effectiveness were evaluated in a single clinical study of 760 patients with previously treated mCRC. Patients were randomly assigned to receive the drug or placebo in addition to best supportive care (BSC).
In January, Bayer said the Phase III CORRECT (colorectal cancer treated with regorafenib or placebo after failure of standard therapy) trial for regorafenib, then known as BAY 73-4506, met its primary endpoint, showing a statistically significant improvement of 29 percent in overall survival in the treatment arm of patients with mCRC.
Findings showed patients treated with regorafenib plus BSC lived a median of 6.4 months compared to a median of five months in those treated with placebo plus BSC.
Results also showed patients treated with regorafenib plus BSC experienced progression-free survival for a median of two months compared to a median of 1.7 months in patients on placebo plus BSC.
Bayer and Onyx gave an early indication of the drug's likely success when, in October 2011, they unblinded the CORRECT study and offered the treatment to patients in the placebo arm at the recommendation of an independent data monitoring committee, based on its interim analysis of the Phase III data.
At the time, the news caught analysts off guard, with BMO Capital Markets biotechnology analyst Jim Birchenough describing the findings as a "major upside surprise." (See BioWorld Today, Oct. 27, 2011.)
On Thursday, J.P. Morgan analyst Cory Kasimov described Stivarga's early approval as "an incremental positive" for Onyx.
"We continue to believe that regorafenib is an underappreciated asset that has been given little credit in both our and Street models," Kasimov wrote. "ONXX now has three approved products, effectively tripling the size of its oncology portfolio in 2012."
The FDA approved Stivarga with a boxed warning on severe and fatal liver toxicity observed during its use in clinical studies.
The most common side effects included weakness or fatigue, loss of appetite, hand-foot syndrome, diarrhea, mucositis, weight loss, infection, high blood pressure and dysphonia.
Stivarga is under review in mCRC by the European Medicines Agency, and the company has filed a new drug application in the U.S. in gastrointestinal stromal tumors, an indication that has orphan drug status and fast-track designation.
"We think [Stivarga] has tremendous opportunity," Campbell said. "We're fully committed to developing this more broadly."
At the end of the day, it was clear Onyx and Bayer partners since 1994 are still friends. Campbell called Nexavar "an important part of our franchise, as well."
Stivarga becomes the second mCRC compound approved by the FDA in as many months. In August, Regeneron Inc.'s Zaltrap (ziv-aflibercept), partnered with Sanofi SA, of Paris, won FDA approval in combination with FOLFIRI (folinic acid, fluorouracil and irinotecan) chemotherapy, a little more than a year after surprising investors with positive data in its pivotal trial. (See BioWorld Today, Aug. 6, 2012.)