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 cancer2 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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EUSA PharmaLee MorleyChief ExecutiveTel +44 (0) 330
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