Servier receives Marketing Authorisation for bowel cancer treatment

Servier receives Marketing Authorisation for LONSURF® (trifluridine/tipiracil)1

New Treatment for Refractory Metastatic Colorectal Cancer

Marketing Authorisation is based on the RECOURSE study results which showed a 2-month improvement in median overall survival (OS) compared to best supportive care (BSC), in patients with refractory metastatic colorectal cancer (mCRC)2

Wexham (UK), 27th April 2016 – Servier today announced that the European Commission has granted a Marketing Authorisation for LONSURF® (trifluridine/tipiracil), formerly known as TAS-102, in the European Union (EU) for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.1 This follows the positive opinion received by the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) in February 2016, which recommended the licensing of trifluridine/tipiracil for the treatment of adult patients with metastatic colorectal cancer (mCRC).3

The Marketing Authorisation is based on data from the international, double-blind, placebo-controlled Phase III RECOURSE study, which investigated the efficacy and safety of trifluridine/tipiracil plus best supportive care (BSC) compared to placebo plus BSC in 800 patients with previously treated mCRC.2 The trial met the primary endpoint of a statistically significant improvement in overall survival (OS).2  The median OS improved from 5.3 months with placebo to 7.1 months with trifluridine/tipiracil, an improvement of 1.8 months.2 The hazard ratio for death in the trifluridine/tipiracil group versus the placebo group was 0.68 (95% confidence interval [CI], 0.58 to 0.81; P<0.001).2 The most frequently observed side effects (≥ 30%) in patients receiving trifluridine/tipiracil were neutropenia, nausea, fatigue, anaemia and leucopenia.2

Dr Mark Saunders, lead Consultant Clinical Oncologist at The Christie’s Colorectal and Peritoneal Oncology Centre said “From my own limited use of this product, and from the clinical trials, Lonsurf appears to be generally well tolerated and to extend the lives of patients with refractory metastatic colorectal cancer. Lonsurf’s mechanism of action means that it is effective in patients regardless of their RAS status or resistance to previous treatments. This could be a valuable new drug and could give my patients some precious extra time.”

An updated analysis of OS was carried out on the RECOURSE population and was presented at the American Society of Clinical Oncology – Gastro Intestinal (ASCO GI) 2016 congress.4 As the updated analysis was conducted at a later time point, it included additional events; 89% of the study population had died at this point compared to 72% at the time of the original analysis.2,4 The results confirmed the clinically meaningful and, statistically significant, survival benefit of trifluridine/tipiracil, providing patients who have exhausted the other treatment options available to them with an improvement of around 2 months in OS (median).4 The median OS was 7.2 months for trifluridine/tipiracil (+BSC) vs 5.2 months for placebo (+ BSC) (HR=0.69; 95% CI: 0.59 to 0.81; p<0.0001), this translated into 1-year survival rates of 27.1% and 16.6%, respectively.4

Trifluridine/tipiracil is now licensed for use in the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein and Norway.1 Availability and funding of trifluridine/tipiracil for patients via the NHS is dependent upon a review by the relevant national Health Technology Appraisal bodies, which is expected to conclude later this year.

ENDS

Notes to Editor

About Metastatic Colorectal Cancer6     

Colorectal cancer (CRC), is the second leading cause of cancer-related deaths in the UK6 and Europe7 wide. In 2012, 215,000 people died from the disease across Europe7, with 16,200 (44/day) of those people being from the UK.7 As such there remains a high unmet need in the treatment of CRC.

There were around 41,100 new cases of colorectal cancer in the UK in 2013, which equates to 110 cases diagnosed every day.6 CRC is the fourth most common cancer in the UK (2013) with 1 in 14 men and 1 in 19 women will be diagnosed with bowel cancer during their lifetime.6

Approximately 25% of patients with CRC present with metastases at initial diagnosis and almost 50% of patients with colorectal cancer will develop metastases.7 When diagnosed at its earliest stage, more than 9 in 10 people with CRC will survive their disease for five years or more, compared with fewer than 1 in 10 people when diagnosed at the latest stage.6

About LONSURF® (trifluridine/tipiracil)

In June 2015, Servier entered into an exclusive licence agreement with Taiho Pharmaceutical Co., Ltd. for the co-development and commercialisation of trifluridine/tipiracil. Under the terms of the agreement, Servier will commercialise trifluridine/tipiracil in Europe and other countries outside of the United States, Canada, Mexico and Asia. Taiho Pharmaceutical retains the right to develop and commercialise trifluridine/tipiracil in the United States, Canada, Mexico, and Asia and to manufacture and supply the product. 

Trifluridine/tipiracil is currently available in Japan for the treatment of unresectable advanced or recurrent CRC and in the United States for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.8,9

Trifluridine/tipiracil is an oral combination anticancer drug of trifluridine (FTD) and tipiracil (TPI), whose primary mechanism of action differs from fluoropyrimidines, which means it is an option for patients resistant to fluoropyrimidines2 FTD is an antineoplastic nucleoside analogue, which is incorporated directly into DNA of cancer cells, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.10 

References

1. Servier Data on File UK16LON0043  

2. Mayer R, et al. N Engl J Med. 2015;372:1909-1919

3. EMA Press Release EMA/CHMP/130102/2016 available at: http://www.ema.europa.eu.  Last accessed April 2016 

4. Mayer R, et al. J Clin Oncol 34, 2016 (suppl 4S; abstr 634) 

5. National Cancer Drugs fund list ver 6.1  available at: https://www.england.nhs.uk/wp-content/uploads/2016/02/ncdf-list-01-02-16.pdf  Last accessed April 2016 

6. Cancer Research UK. Bowel Cancer Statistics. Available at: http://www.cancerresearchuk.org/healthprofessional/bowelcancerstatistics#headingSix  Last accessed February 2016 

7. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2014) 25 (suppl 3): iii1-iii9. 

8. FDA News Release. FDA approves new oral medication to treat patients with advanced colorectal cancer. 22 September 2015. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm463650.htm  Last accessed April 2016 

9. Taiho Pharma. Taiho's Lonsurf® (trifluridine and tipiracil hydrochloride) Tablets Approved in Japan for Treatment in Advanced Metastatic Colorectal Cancer. Available at: http://www.taiho.co.jp/english/news/20140324.html Last accessed April 2016  

10. Lenz HJ, Stintzing S, Loupakis F. Cancer Treatment Reviews. 2015. 41:777-783 

Code: UK16LON0035  Date of Preparation: April 2016

 

 

UK16WEB0002 DoP: May 2016