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Date: 2017-06-22

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Fotivda®

Compound: tivozanib - N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N´-(5-methyl-3-isoxazolyl) urea hydrochloride monohydrate

Therapeutic area: Cancer - Oncology

Action mechanism: kinase inhibitor/tyrosine kinase inhibitor. Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) with a long half-life and activity against all three VEGF receptors.

Company: Aveo Oncology (USA - MA) Eusa Pharma (UK)

Disease: first-line treatment of advanced renal cell carcinoma (RCC)

Latest news:

  • • On June 22, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Fotivda®, for the treatment of advanced renal cell carcinoma. The drug will be available as 890 µg and 1340 µg hard capsules. The benefits with Fotivda® are its ability to improve progression-free survival in patients with advanced disease. The most common side effects are hypertension, dysphonia, fatigue and diarrhoea.
  • The full indication is: "first line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC." It is proposed that Fotivda be prescribed by physicians experienced in the treatment of cancer.
  • • On April 13, 2017, Aveo Oncology announced that its European licensee for tivozanib, EUSA Pharma, has submitted responses to the European Medicines Agency (EMA) Day 180 List of Outstanding Issues (LOI) related to the Marketing Authorization Application (MAA) for tivozanib as a first-line treatment for renal cell carcinoma. With submission of the response complete, EUSA remains tentatively scheduled to provide an oral explanation to the EMA’s Committee for Medicinal Products for Human Use (CHMP) at its May 2017 meeting. As previously announced, the Day 180 LOI signified that the MAA is not approvable at that time, and outlines outstanding deficiencies, which are then required to be satisfactorily addressed in an oral explanation and/or in writing prior to a final application decision.• On November 28, 2016, Aveo Oncology announced that its development partner, EUSA Pharma has submitted its responses to the European Medicines Agency (EMA) Day 120 List of Questions. The Day 120 List of Questions were issued by the Committee for Medicinal Products for Human Use (CHMP) as part of the centralized review process of the Marketing Authorization Application (MAA) for tivozanib for the first-line treatment of advanced renal cell carcinoma (RCC). The next step in the filing process, the EMA Day 180 List of Outstanding Issues, is expected in the first quarter of 2017.
  • • On March 1, 2016, EUSA Pharma and AVEO Oncology announced the submission of a Marketing Authorization Applicatio to the European Medicines Agency for tivozanib for the first-line treatment of advanced renal cell carcinoma. The filing is based on tivozanib’s existing dataset and follows positive interactions with the Rapporteur and Co-Rapporteur during 2015 which indicated support for a filing using the phase III TIVO-1 trial as the pivotal study. EUSA Pharma submitted the application under the European Union’s centralized procedure. Under the companies’ license agreement announced in December 2015, EUSA holds exclusive commercialization rights to tivozanib in RCC in Europe and in a number of other territories outside North America, including South America and South Africa, in addition to a range of further indications. Under the terms of the agreement, EUSA Pharma will undertake and fund the commercialization of the product in its territories, assuming approval. Aveo Oncology also intends to initiate a Phase 3 trial of tivozanib in third line RCC to potentially enable registration in the first- and third-lines in the U.S.
  • • On June 3, 2015, Aveo Oncology announced that, following pre-submission advisory meetings to discuss the potential submission of a Marketing Authorization Application for tivozanib in Europe for the treatment of renal cell carcinoma, it has received written confirmation of support from the Rapporteur and co-Rapporteur for the filing of such an application. The Rapporteur (from Portugal) and Co-Rapporteur (from the United Kingdom) are the two appointed members of the Committee for Medicinal Products for Human Use (CHMP) who would lead the evaluation of the MAA, if submitted. The application would be based on the Company’s existing dataset, which includes results from the Phase 3 TIVO-1 study of tivozanib in the first-line treatment of RCC in which tivozanib demonstrated a significant improvement over sorafenib in the study’s primary endpoint of progression free survival. At the advisory meetings, Aveo provided data demonstrating that the discordance in overall survival (OS), the secondary endpoint of the study, was very likely attributable to the crossover design of the study. The final meeting minutes reflect that the Rapporteurs “did not see a ‘blocking issue’ with the OS trend” and that Aveo “clearly presented a credible story for the Rapporteurs to assess but one which would need to be supported with very careful reasoning.” Aveo was also reminded that the Rapporteurs “cannot advise on [the] final outcome of the review.”
  • • On January 8, 2015, Aveo Oncology announced that it has received written confirmation from the European Medicine Agency (EMA) that tivozanib is eligible for submission of an application for a European Union Marketing Authorization under the Agency’s centralized procedure. Confirmation of eligibility was given in response to the submission of a letter of intent enabling the Company to evaluate the opportunity for submitting a Marketing Authorization Application (MAA) for tivozanib with the EMA for the treatment of renal cell carcinoma (RCC). The letter of intent, which must be filed at least seven months prior to submission of a MAA, initiates the process to address a number of pre-submission requirements, including the assignment of a Rapporteur and Co-Rapporteur, who are two appointed members of the CHMP. Aveo recently entered into an option agreement with Ophthotech to investigate tivozanib for the potential treatment of non-oncologic diseases of the eye, and the Company is actively pursuing partnerships to advance the development of tivozanib in solid tumors.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE: 2016-03-01

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization:

UE authorization:

Favourable opinion UE: 2017-06-22

Favourable opinion USA:

Orphan status USA:

Orphan status UE: 2010-06-09

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes