HEMEL HEMPSTEAD, England–(BUSINESS WIRE)– EUSA Pharma (EUSA), a specialty pharmaceutical company with a focus on oncology and oncology supportive care, today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending marketing authorisation of FOTIVDA (tivozanib) for the management of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. If approved, it will be indicated for the first-line treatment of adult patients with advanced 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. ¹

RCC is the most common form of kidney cancer, ² which accounts for an estimated 49,000 deaths in Europe each year. ³ It is expected to be one of the fastest increasing cancers over the next ten years. ⁴ Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are currently the gold standard first-line treatment for advanced RCC in Europe, however, patients on existing treatments can often experience significant side effects. ^5,6

The CHMP’s recommendation is based on data from the global, open-label, randomised, multi-centre Phase III trial (TiVO-1) ^1,5 which evaluated the efficacy and tolerability of tivozanib compared to a currently available comparator VEGFR-TKI treatment (sorafenib) in the treatment of over 500 patients with advanced RCC. The trial met its primary endpoint demonstrating the longest median progression-free survival (PFS) seen with a VEGFR-TKI in a first-line phase III clinical study in 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. ^1,5 There was also an improved side effect profile with tivozanib, meaning 86% of patients were able to remain on full dose (versus 57% with sorafenib, P = <0.001), with only 14% (versus 43% with sorafenib) requiring a dose reduction due to adverse events (AEs). In addition, fewer people on tivozanib experienced the burdensome side effects, commonly associated with other VEGFR-TKIs, such as diarrhoea (23% vs 33%), and hand-foot syndrome (14% vs 54%). ⁵

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, although currently available therapies can be associated with burdensome toxicities. We are still in need of effective and well tolerated new treatments in metastatic RCC and thus, tivozanib will be a welcomed addition. We also look forward to continuing our investigations of potential combination approaches with other therapeutic agents.”

Tivozanib is an oral, once-daily, potent and highly-selective VEGFR-TKI. Current first-line VEGFR-TKIs block the action of a broad range of Tyrosine Kinases (TKs), in addition to the VEGFR targets, which can lead to patients experiencing burdensome side effects. ^5,6

“Today’s opinion by the CHMP to recommend marketing authorisation of tivozanib in the EU is an important step in expanding treatment options for patients with advanced renal cell carcinoma, where, despite advancements in therapy, survival rates in advanced disease remain low and existing treatments can be associated with therapy-limiting toxicities,” said Dr Jon Morgan, Medical Director, EUSA Pharma. “The opinion is supported by robust and consistent results from the TiVO-1 pivotal study which demonstrated compelling efficacy of tivozanib as a first-line treatment, and importantly for this class of agents, a highly favourable and advantageous tolerability profile.”

Lee Morley, EUSA Pharma’s Chief Executive Officer said, “Tivozanib has the potential to become an important new first-line therapy and this positive CHMP outcome represents a great achievement for the EUSA team. Along with the recent EU approval of dinutuximab beta, EUSA is making great strides in building a leading specialty pharmaceutical business. In our short history we have made significant progress in expanding our portfolio of specialist medicines, and we look forward to further strengthening our portfolio focused in the oncology field.”

Following the CHMP positive opinion, the European Commission will now issue a formal decision on approval, and if approved, tivozanib will be indicated for use in the 28 countries in the European Union plus Iceland and Norway.

-ENDS-

NOTES TO EDITORS

About tivozanib and renal cell carcinoma (RCC)

Kidney cancer is the seventh most common cancer in Europe, with more than 115,000 new cases diagnosed each year. ⁷ RCC is the most common form of kidney cancer ² with RCC accounting for around 80% of all kidney cancers. ⁸ Kidney cancer is expected to be one of the fastest increasing cancers over the next ten years, as a result of Europe’s ageing population, with smoking and a rise in obesity also playing a part. ⁴

An over-expression of VEGF protein, and a resulting increase in tumour blood supply (angiogenesis), is a common feature of RCC. ⁵ VEGFR-TKIs reduce the supply of blood to the tumour and are the gold standard first-line treatment for advanced RCC in Europe, however, patients on current treatments often experience significant side effects, including skin rashes, diarrhoea, and hand-foot syndrome.

In the global Phase III trial (TiVO-1) ⁵ in advanced RCC, tivozanib demonstrated a significant PFS benefit versus sorafenib (11.9 vs. 9.1 months in the overall patient 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]). ^1,5 There was also an improved side-effect profile versus sorafenib, with significantly fewer patients on tivozanib (14% versus 43%) requiring a dose reduction due to AEs; and less than 5% of patients experiencing the severe side effects (grade 3&4) commonly associated with other VEGF-TKIs, such as diarrhoea, asthenia (physical weakness) and hand-foot syndrome. Hypertension (44%) and dysphonia (21%) were the most commonly reported AEs on tivozanib. ⁵

Under EUSA’s license agreement with AVEO PHARMACEUTICALS, INC, announced in December 2015, the company holds exclusive commercialisation 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 commercialisation of the product in its territories, assuming approval. AVEO PHARMACEUTICALS, INC retains the rights to commercialise the product in North America.

About EUSA Pharma

Founded in March 2015, EUSA Pharma is a specialty pharmaceutical company. The company has commercial operations in the US and Europe, and a wider distribution network in approximately 40 countries around the world. Currently, EUSA has a portfolio of approved and several named-patient specialty hospital products, which the company has ambitious plans to expand through acquisition and in-licensing. EUSA is led by an experienced management team with a strong record of building successful specialty pharmaceutical companies, and is supported by significant funding raised from leading life science investor EW Healthcare Partners.

EUSA Pharma’s products include: Caphosol® dispersible for the treatment of oral mucositis, a common and debilitating side-effect of radiation therapy and high-dose chemotherapy; Collatamp®, a gentamicin-collagen implant licensed either in haemostasis or for the prevention and treatment of surgical site infection; Custodiol® solution for use in the preservation of organs for transplantation; Fomepizole for the treatment of ethylene glycol poisoning; Xenazine® for the treatment of movement disorders associated with Huntington’s chorea; and Dinutuximab beta for the treatment of patients with high-risk neuroblastoma.

For more information visit www.eusapharma.com.

About AVEO

AVEO PHARMACEUTICALS, INC is a biopharmaceutical company dedicated to advancing a broad portfolio of targeted therapeutics for oncology and other areas of unmet medical need. The company is focused on developing and commercialising its lead candidate tivozanib, a potent, selective, long half-life inhibitor of vascular endothelial growth factor, 1, 2 and 3 receptors, in North America as a treatment for renal cell carcinoma and other cancers. AVEO is leveraging multiple partnerships to develop and commercialise tivozanib in non-oncologic indications worldwide and oncology indications outside of North America, as well as to progress its pipeline of novel therapeutic candidates in cancer and cachexia (wasting syndrome). For more information, please visit the company’s website at www.aveooncology.com.

References

¹ Committee for Medicinal Products for Human Use (CHMP). Summary of opinion to be made. Available at: http://www.ema.europa.eu

² Cancer Research UK. Kidney Cancer, Types and Grades. Available at: http://www.cancerresearchuk.org/about-cancer/kidney-cancer/stages-types-grades/types-grades. Last accessed June 2017.

³ Cancer Research UK. Kidney Cancer Statistics. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer/mortality#heading-Five . Last accessed June 2017.

⁴ Cancer Research UK. Kidney cancer rates are increasing, so what’s fuelling the surge? Available at: http://scienceblog.cancerresearchuk.org/2017/04/24/kidney-cancer-rates-are-increasing-so-whats-fuelling-the-surge/. Last accessed June 2017.

⁵ Motzer R.J; Nosov D et al. Tivozanib Versus Sorafenib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma: Results From a Phase III Trial. Journal of Clinical Oncology. Volume 31. 2013: 30:3791

⁶ Wong MKK, Mohamed AF et al. Selecting renal cell carcinoma therapy: Ranking of patient perspective on toxicities. J Clin Oncol 30: 303s, 2012 (suppl; abstr 4608)

⁷ http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer/incidence#heading-Ten. Last accessed June 2017.

⁸ Escudier B; Porta C et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 27 (Supplement 5). 2016: v58–v68. Available at: http://www.esmo.org/Guidelines/Genitourinary-Cancers/Renal-Cell-Carcinoma. Last accessed June 2017.

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Contacts

EUSA Pharma
Lee Morley
Chief Executive
Tel +44 (0) 330 5001140