With Stronger OS Data, AVEO Plans to Seek Approval of RCC Drug Tivozanib

Clinical Trials Research

Shares of AVEO Oncology are climbing fast in premarket trading after the company released data that showed positive overall survival benefits of tivozanib in patients with highly refractory metastatic renal cell carcinoma who have received prior immunotherapy treatments.

Cambridge, Mass.-based AVEO announced results from the second prespecified analysis of overall survival (OS) in its Phase III TIVO-3 trial that compared tivozanib to Nexavar (sorafenib). The data showed a hazard ratio of less than one, which is cause for excitement for the company. For AVEO, this news has been long-awaited as the company was forced to delay seeking approval of tivozanib in this indication. During the Phase III study, tivozanib met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival. However, a preliminary analysis of the secondary endpoint of overall survivability showed a hazard ratio greater than one. The OS concerns caused the company to delay its planned New Drug Application with the U.S. Food and Drug Administration until the fourth quarter of this year. That decision was based on a recommendation from the FDA that the company not seek regulatory approval of tivozanib until “more mature” results regarding overall survival in patients were available.

When the Phase III results were first released, in 2018, tivozanib met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival. AVEO said tivozanib demonstrated a 44 percent improvement in median PFS and 26 percent reduction in risk of progression or death in dosed patients. Median progression-free survival was 5.6 months for tivozanib compared to 3.9 months for sorafenib, the company said. With the latest news, AVEO has even stronger data in hand. The data cutoff date for the second prespecified analysis was Aug. 15, two years from the last patient enrolled and approximately 10 months from the data cut-off date for the first prespecified analysis. Between the two data cut-off dates, 16 additional OS events were reported on the tivozanib arm and 28 on the sorafenib arm, resulting in a total of 114 OS events on the tivozanib arm and 113 on the sorafenib arm. Median OS was 16.4 months for tivozanib and 19.7 months for sorafenib, the company said. In addition to the OS results, the latest analysis also revealed some significant progression-free survival results. AVEO said 20 patients who were on the tivozanib arm remained progression-free in comparison to two patients on the sorafenib arm with a median duration of 32.5 months.

Brian Rini, director of the Cleveland Clinic Genitourinary Cancer Program and principal investigator of the TIVO-3 trial, noted that the study included the first data to demonstrate durable improvements in this highly refractory advanced kidney cancer population, including the post-immunotherapy setting.

Michael Bailey, president and chief executive officer of AVEO, said he is pleased to see the positive PFS and overall response rate, which was previously shown when the Phase III data was first announced, “have translated into an improved OS hazard ratio.” Bailey said the company looks forward to moving forward to discussing the results with the FDA.

Aveo’s tivozanib is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor. It has been approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland and is sold under the name Fotivda.

The tivozanib delays this year have caused unrest among AVEO investors. Since the company announced it had delayed its NDA in January, the stock has lost more than half of its value. In premarket trading, the stock has climbed to 91 cents per share.

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