AVEO Pharmaceuticals, Inc. (NASDAQ:AVEO) share are climbing nearly 9% in pre-market trading Monday, after the drug maker announced that the European Commission (EC) has approved FOTIVDA® (tivozanib) for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland.
Tivozanib is indicated for the first line treatment of adult patients with advanced RCC and for adult patients who are vascular endothelial growth factor receptor (VEGFR) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC.i EUSA Pharma, a specialty pharmaceutical company with a focus on oncology and oncology supportive care, is the European licensee for tivozanib. Tivozanib is an oral, once-daily, potent and highly-selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI).
Dr. Bernard Escudier, Medical Oncologist and member of the Genitourinary Tumour Board of Gustave Roussy, France, commented “This is excellent news for patients with metastatic RCC. Outcomes in this disease have greatly improved with the introduction of targeted therapies, meaning that patients are living for longer. However, we are still in need of effective and well tolerated new treatments in metastatic RCC and thus, tivozanib is a welcomed addition.”
The approval from the EC follows the recommendation from the Committee for Medical Products for Human Use (CHMP).i1 The decision was primarily based on data from a global, open-label, randomized, multi-center Phase 3 trial (TIVO-1)i,iii which evaluated the efficacy and tolerability of tivozanib compared to a currently available comparator VEGFR-TKI treatment (sorafenib) in 517 patients with advanced RCC. Patients treated with tivozanib experienced superior PFS (11.9 vs. 9.1 months in the overall population [HR, 0.797; 95% CI, 0.639 to 0.993; P =.042] and 12.7 vs. 9.1 months in treatment naïve patients [HR, 0.756; 95% CI, 0.580 to 0.985; P =.037]) versus sorafenib.iii There was also an improved side effect profile with tivozanib, with only 14% (versus 43% with sorafenib) requiring a dose reduction due to adverse events (AEs). In addition, fewer people on tivozanib experienced burdensome side effects, such as diarrhea (23% vs 33%) and hand-foot syndrome (14% vs 54%).iii
EUSA Pharma has indicated that it intends to now work with the necessary health authorities to make tivozanib available to advanced RCC patients across Europe as quickly as possible.
“The European Commission’s decision is the first regulatory approval of tivozanib globally, and a tremendous accomplishment for AVEO and its partner, EUSA Pharma. We are very pleased that tivozanib is now available to patients in Europe,” said Michael Bailey, president and chief executive officer of AVEO. “We also continue to make progress on the next two pillars in our tivozanib strategy: U.S. registration, driven by the pivotal Phase 3 TIVO-3 trial, which is expected to read out in the first quarter of 2018; and immunotherapy combination trials, starting with the TiNivo trial, our Opdivo® combination trial. European approval further strengthens our balance sheet by triggering an R&D payment to AVEO and provides AVEOthe opportunity to achieve multiple potential commercial milestone payments, as well as royalty payments on sales, that would support our execution of the tivozanib strategy.”
Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay AVEOup to $394 million in future milestone payments and research and development funding, assuming successful achievement of specified development, regulatory and commercialization objectives. In addition, a tiered royalty will be due to AVEO ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. European marketing approval for tivozanib triggers a $4 million research and development payment from EUSA, and AVEO will also be eligible for up to $12 million in additional milestones from EUSA based on reimbursement and regulatory approvals. In the territories licensed to EUSA, thirty percent of milestone and royalty payments received by AVEO, excluding research and development funding, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee. In the territories retained by AVEO, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.
AVEO Pharmaceuticals, Inc. operates as a biopharmaceutical company, which engages in the advancement of therapeutics for oncology and other areas of unmet medical need. Its products include Tivozanib, Ficlatuzmab, AV-203, AV-380, and AV-353. It focuses on the development of its lead candidate, Tivozanib, in North America as a treatment for renal cell carcinoma and other cancers.