On August 4, 2014 Infinity Pharmaceuticals reported that the company has purchased an option to buy out all future potential royalty payments due to Millennium: The Takeda Oncology Company for sales in oncology of IPI-145, Infinity’s oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma (Press release Infinity Pharmaceuticals, AUG 4, 2014, View Source [SID:1234500682]).

In exchange for a one-time, upfront payment of $5.0 million, Infinity receives an option to terminate its obligation to pay Millennium future royalties related to the sale of IPI-145 in oncology. Infinity may exercise this option by providing written notice and payment to Millennium of a one-time exercise fee of $52.5 million on or before March 31, 2015. Exercise of the option does not affect any other obligation under the Development and License Agreement, including Infinity’s obligation to pay royalties on sales of IPI-145 outside of oncology. If Infinity does not exercise the option, its royalty obligations with respect to IPI-145 in oncology will remain in effect.

Assuming exercise of the option, Infinity’s obligation to pay Millennium tiered royalties, ranging from seven percent to 11 percent, on worldwide net sales of Infinity’s first two distinct PI3K product candidates will exclude worldwide net sales of IPI-145 in oncology. Infinity will remain obligated to pay milestones to Millennium for Infinity’s first two distinct PI3K product candidates that gain approval, including IPI-145. The remaining milestones comprise up to a total of $220 million in success-based regulatory milestones, up to a total of $230 million in commercial milestones which are due once certain sales thresholds have been met, and up to a total of $5 million in development milestones.

On August 4, 2014 Amgen and its subsidiary, Onyx Pharmaceuticals, reported that a planned interim analysis demonstrated that the Phase 3 clinical trial ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) met its primary endpoint of progression-free survival (PFS) (Press release Amgen, AUG 4, 2014, View Source [SID:1234500669]). Patients treated with Kyprolis (carfilzomib) for Injection in combination with Revlimid (lenalidomide) and low-dose dexamethasone (KRd) lived significantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexamethasone (Rd) (median 17.6 months) (HR=0.690, 95 percent CI, 0.570, 0.834, p<0.0001). While the data for overall survival, a secondary endpoint, are not yet mature, the analysis showed a trend in favor of KRd that did not reach statistical significance. The safety profile observed in this study is consistent with the current U.S. Kyprolis label, including the rate of cardiac events. Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. No new safety signals were identified. Results will be submitted for presentation at the upcoming 56th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) later this year. "We are excited about these clinical results and the positive prospects they suggest for patients with multiple myeloma," said Robert A. Bradway, chairman and chief executive officer of Amgen, adding, "Our mission at Amgen is to serve patients by advancing medicines that address serious disease. Kyprolis is an important building block in our robust, differentiated pipeline." Bradway further explained, "Coupled with our recent U.S. regulatory submissions for ivabradine and talimogene laherparepvec and our upcoming regulatory submissions for evolocumab and blinatumomab, our pipeline continues to show notable progress." Results from the ASPIRE study will form the basis for regulatory submissions throughout the world beginning in the first half of 2015. In the U.S., the data may support the conversion of accelerated approval to full approval and expand the current indication. "In the treatment of patients with multiple myeloma, periods of remission become shorter following each treatment regimen, underscoring the need for new options. The results of the ASPIRE study demonstrate that Kyprolis can significantly extend the time patients live without their disease progressing," said Pablo J. Cagnoni, M.D., president, Onyx Pharmaceuticals, Inc. "The ability of novel therapies to produce deep and durable responses may, one day, transform this uniformly fatal disease to one that is chronic and manageable." Onyx conducted the ASPIRE study under a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration (FDA) and has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the study. About ASPIRE The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated Kyprolis in combination with lenalidomide and low-dose dexamethasone, versus lenalidomide and low-dose dexamethasone alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. Secondary endpoints included overall survival, overall response rate, duration of response, disease control rate, health-related quality of life, and safety. Patients were randomized to receive Kyprolis (20mg/m2 on days 1 and 2 of cycle 1 only, then 27mg/m2 subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40mg per week in 4 week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe, and Israel.