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.

On July 31, 2014 ZIOPHARM Oncology, Inc. (“ZIOPHARM”) (Nasdaq: ZIOP), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, and Solasia Pharma K.K. (“Solasia”), a developer of oncology pharmaceuticals in-licensed for commercialization in major markets throughout the world, reported an amendment and restatement of their License and Collaboration Agreement for darinaparsin (Zinapar or ZIO-101) and related organoarsenic molecules (Press release, Solasia, JUL 31, 2014, View Source [SID1234520951]).

Under the terms of the amended and restated agreement, ZIOPHARM granted Solasia an exclusive worldwide license to develop and commercialize darinaparsin, and related organoarsenic molecules, in both intravenous and oral forms in all indications for human use. In exchange, ZIOPHARM will be eligible to receive from Solasia up to $72.2 million in development-and sales-based milestones, a royalty on net sales of darinaparsin, once commercialized, and a percentage of any sublicense revenues generated by Solasia. Solasia will be responsible for all costs related to the development, manufacturing and commercialization of darinaparsin. The new agreement amends and restates a 2011 agreement between the parties under which Solasia was granted exclusive rights by ZIOPHARM to darinaparsin in the territories of Japan, China, Hong Kong, Macau, Republic of Korea, Taiwan, Singapore, Australia, New Zealand, Malaysia, Indonesia, Philippines and Thailand.

Darinaparsin is a novel mitochondrial-targeted agent (organoarsenic) being developed for the treatment of various hematologic and solid cancers. It has been granted Orphan Drug Designation in the U.S. and Europe as a treatment of peripheral T-cell lymphoma (PTCL).

“As our strategic focus has shifted exclusively toward DNA therapeutics and immuno-oncology, Solasia, with whom ZIOPHARM has had a longstanding partnership, is the natural choice to advance the development of darinaparsin on a global basis,” said Jonathan Lewis, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. “Through a collaboration that began in 2011, Solasia has built a meaningful scientific and clinical understanding of darinaparsin, providing a strong foundation for realizing its long-term clinical value. Further, by expanding this agreement to all global territories, there exists now an additional strong incentive for Solasia to rapidly and strategically develop this potentially important product candidate in areas of unmet medical need in oncology.”

“Solasia stands to benefit greatly from the acquisition of exclusive global development and commercialization rights to darinaparsin from ZIOPHARM,” said Yoshihiro Arai, President and Representative Director of Solasia Pharma K.K. “Our initial Asian clinical studies with darinaparsin in the clinical setting of PTCL have been very exciting and encouraged us to expand our longstanding partnership with ZIOPHARM in order to maximize our opportunity with
the darinaparsin program throughout the world. We presently plan to start pivotal clinical trials in Asia early in 2015.”