U.S. Food and Drug Administration Approves Tivozanib for Relapsed or Refractory Advanced RCC

According to a press release from AVEO Oncology, “On March 10’th, 2021, the FDA has granted approval to tivozanib (Fotivda), is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), as a treatment for the adult patients with relapsed/refractory advanced renal cell carcinoma (RCC) who were given 2 or more prior systemic therapies. 

The approval of tivozanib is based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing tivozanib to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies, including at least 1 VEGFR kinase inhibitor excluding sorafenib or tivozanib. Patients were randomized to either tivozanib 1.34 mg orally once daily for the 21 consecutive days every 28 days or sorafenib 400 mg orally twice daily continuously, until the disease progression or unacceptable toxicity.

The primary efficacy outcome measure was PFS (Progression-free Survival), assessed by a blinded independent radiology review committee. Other efficacy endpoints were OS (Overall Survival) and ORR (Objective Response Rate).

Median progression free survival was noted as 5.6 months (95% CI: 4.8, 7.3) in the tivozanib arm (n=175) in comparison to the 3.9 months (95% CI: 3.7, 5.6) for those who were given sorafenib (HR 0.73; 95% CI: 0.56, 0.95; p=0.016). Median overall survival was noted as 16.4 (95% CI: 13.4, 21.9) and 19.2 months (95% CI: 14.9, 24.2), for the tivozanib and sorafenib arms, respectively (HR 0.97; 95% CI: 0.75, 1.24). The Overall Response Rate was noted as 18% (95% CI: 12%, 24%) for the arm of tivozanib and 8% (95% CI: 4%, 13%) for the arm of sorafenib.  

The most commonly reported (≥20%) adverse reactions were hypertension, fatigue, diarrhea, nausea, dysphonia, decreased appetite, cough, hypothyroidism, and stomatitis. The most common grade 3/4 laboratory abnormalities (≥5%) were increased lipase, decreased phosphate, and decreased sodium. 

The recommended dose of tivozanib is 1.34 mg once daily (either with or without food) for 21 consecutive days (3 weeks) every 28 days until disease progression or unacceptable toxicity.

The Food and Drug Administration approval of tivozanib represents an absolutely exciting, meaningful advancement by providing a new treatment option for r/r Renal Cell Carcinoma.

AVEO plans to make tivozanib available to patients in the U.S. by March 31’st, 2021.

Reference:

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma?utm_medium=email&utm_source=govdelivery

Off-topic

About Tivozanib (Fotivda):

Tivozanib basically is an oral, next-generation VEGFR tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed in order to enhance efficacy as well as tolerability.

AVEO got the U.S. FDA approval for tivozanib in order to treat adult patients with r/r advanced renal cell carcinoma (RCC) following a couple of or more prior systemic therapies. 

Earlier in August 2017, Tivozanib was approved in the EU and other countries in the territory of its partner EUSA Pharma (UK) Limited in order to treat adult patients with advanced Renal Cell Carcinoma. This medication has been demonstrated to significantly decrease regulatory T-cell production in the preclinical models. 
Indication: As an oral VEGF receptor tyrosine kinase inhibitor, Tivozanib is used in order to treat adult patients with relapsed or refractory advanced RCC following two or more prior systemic therapies.