Onyx Wins Accelerated Nod for Myeloma Drug Kyprolis

By Jennifer Boggs
Managing Editor

Shares of Onyx Pharmaceuticals Inc. jumped 11.7 percent Friday after its multiple myeloma drug Kyprolis (carfilzomib) won accelerated approval as a third-line treatment.

The stock (NASDAQ:ONXX) closed at $76.38, up $7.98.

The approval, which came a week ahead of the drug's July 27 PDUFA date, offers a new therapy for a subset of myeloma patients who have run out of treatment options, Onyx's president and CEO, Tony Coles, told investors during a conference call.

That unmet need is what prompted an 11-0 vote from the FDA's Oncologic Drugs Advisory Committee (ODAC) in favor of Kyprolis last month, despite concerns raised by FDA reviewers over severe cardiac toxicities and the possibility that the second-generation proteasome inhibitor might not offer an advantage over existing multiple myeloma therapies. The agency had even declined to grant the Kyprolis application priority review when Onyx submitted the application last year, setting up a standard 10-month review timeline rather than six months. (See BioWorld Today, Dec. 13, 2011, June 19, 2012, and June 21, 2012.)

Had the agency split with ODAC and refused to grant accelerated approval, South San Francisco-based Onyx would have had to complete a confirmatory trial before filing the new drug application (NDA), which would have delayed approval until 2014 or 2015.

Kyprolis is indicated for patients who have received at least two prior therapies, including treatment with multiple myeloma staple Velcade (bortezomib, Millennium: The Takeda Oncology Co.) and an immunomodulatory therapy, and have demonstrated disease progression on or within 60 days of completion of the last therapy. That means about 10,000 to 15,000 patients will be eligible for treatment in the U.S. on an annual basis, said Helen Torley, Onyx executive vice president and chief commercial officer. "There is no standard of care in this setting today, and patients have limited treatment options," she added.

Onyx, which holds full worldwide rights to Kyprolis, excluding Japan, has been gearing up for an immediate launch. Torley said a 100-member sales team will begin making calls next week, with Kyprolis available to patients by Aug. 1. She noted that the Kyprolis sales group is separate from Onyx's sales team for its kinase franchise, which includes Nexavar (sorafenib), the blockbuster cancer drug partnered with Bayer AG.

Onyx has set pricing for Kyprolis at $1,658 per vial, or about $9,950 per cycle. The firm was reluctant to speculate on what that could translate to on a per-patient basis, though executives noted that patients underwent a median treatment duration of about 4.4 months in clinical trials.

Based on the premium pricing, Cowen and Co. analyst Phil Nadeau is projecting 2013 Kyprolis sales to reach $200 million, with sales in the U.S. jumping to $750 million in 2016.

The accelerated approval was based on data from the single-arm Phase IIb trial in 266 heavily pretreated patients with relapsed or refractory multiple myeloma. Results showed an overall response rate of 24 percent and a median duration of response of 7.8 months. (See BioWorld Today, Sept. 29, 2011.)

Naturally, Onyx will have to complete several postmarketing requirements, but Barbara Klencke, senior vice president of clinical development, told investors that the three Phase III studies currently under way should help the firm meet most of those requirements.

Onyx has completed enrollment in the Phase III ASPIRE trial, which is testing Kyprolis in combination with Revlimid (lenalidomide, Celgene Corp.) and low-dose dexamethasone vs. Revlimid and dexamethasone alone in relapsed multiple myeloma patients who have received one to three prior therapies. That trial is being conducted under a special protocol assessment with the FDA.

A second study, dubbed ENDEAVOR, is testing Kyprolis plus low-dose dexamethasone head to head against Velcade plus low-dose dexamethasone. And the third trial, FOCUS, is evaluating Kyprolis as a single agent in patients with relapsed and refractory disease who have received one to three prior therapies.

Earlier in development, Kyprolis is being tested in a Phase I/II study by Onyx's Japanese partner, Ono Pharmaceutical Co. Ltd., in relapsed and refractory Japanese patients.

"So this is just the beginning," Klencke said.

Onyx gained rights to Kyprolis through its 2009 acquisition of Proteolix Inc. in an $851 million deal in which Onyx paid $276 million up front, with the rest in milestones, including a $170 million milestone due to Proteolix shareholders upon accelerated FDA approval. (See BioWorld Today, Oct. 13, 2009.)

Another beneficiary of Kyprolis' approval is Ligand Pharmaceuticals Inc., which contributed its Captisol technology – acquired in the 2011 buyout of CyDex Pharmaceuticals Inc. – for the drug's formulation. Under the terms of the deal, La Jolla, Calif.-based Ligand is entitled to milestone payments and royalties on Kyprolis sales.

Shares of Ligand (NASDAQ:LGND) closed Friday at $17.51, down 2 cents.