Business Wire

European Medicines Agency To Start the Review of The Marketing Authorization Applications for Encorafenib and Binimetinib For the Treatment Of BRAF-Mutant Advanced Melanoma

Del

Pierre Fabre Laboratories the 2nd largest private French pharmaceutical group today announced that the European Medicines Agency (EMA) has validated the review of the Marketing Authorization Applications (MAAs) for the use of the combination of binimetinib 45 mg twice daily and encorafenib 450 mg once daily (COMBO450) for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The submissions are supported by data from the pivotal Phase 3 COLUMBUS study, which showed that patients who received the combination of binimetinib and encorafenib had a significantly longer progression free survival (PFS) compared to patients receiving vemurafenib.

"COLUMBUS results, including progression free survival, objective response rate, dose intensity and tolerability of the combination, provide a strong and consistent theme across multiple endpoints for this study. We are pleased that the EMA has initiated its review of the MAAs of binimetinib and encorafenib. If approved, the combination, co-developed with Array BioPharma, would represent a new and potentially important option for patients with BRAF-mutant advanced melanoma," said Frederic Duchesne, President & CEO Pierre Fabre Pharmaceuticals Division.

COLUMBUS Results
As presented at the 2016 Society for Melanoma Research Annual Congress, results from Part 1 of the COLUMBUS study showed that COMBO450 significantly extend PFS in patients with advanced BRAF-mutant melanoma, with a PFS of 14.9 months compared with 7.3 months observed with vemurafenib and provides a meaningful 46% risk reduction in disease progression or death [hazard ratio (HR) 0.54, (95% CI 0.41-0.71, P<0.001)]. As part of the trial design, the primary analysis was based on a Blinded Independent Central Review (BICR) of patient scans, while results by local review at the investigative site were also analyzed.
The combination of encorafenib plus binimetinib also demonstrated an improvement in confirmed overall response rate (ORR; complete response plus partial response) versus Vemurafenib (63% versus 40%)

In this study, COMBO450 was generally well-tolerated allowing a median relative dose intensity for encorafenib and binimetinib of 100% and 99.6%, respectively while the median duration or treatment was 51 weeks. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving COMBO450 were increased gamma-glutamyltransferase (GGT) (9%), increased blood creatine phosphokinase (CK) (7%), and hypertension (6%). The incidence of selected any grade of AEs of special interest, defined based on toxicities commonly associated with commercially available MEK+BRAF-inhibitor treatments for patients receiving COMBO450 included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were presented at the 2016 Society for Melanoma Research Annual Congress.

About the Phase 3 COLUMBUS Study
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 study evaluating the efficacy and safety of the combination of binimetinib plus encorafenib to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAF V600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the study. Patients were randomized into two parts:

  • In Part 1, 577 patients were randomized 1:1:1 to receive 45mg binimetinib twice daily plus 450mg encorafenib once daily (COMBO450), 300mg encorafenib alone once daily, or 960mg vemurafenib alone twice daily. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was a PFS comparison of COMBO450 versus vemurafenib. PFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the PFS of encorafenib monotherapy to that of COMBO450 and a comparison of overall survival (OS) for COMBO450 to that of vemurafenib alone.
  • In Part 2, 344 patients were randomized 3:1 to receive 45mg binimetinib twice daily plus 300mg encorafenib once daily or 300mg encorafenib alone once daily. Part 2 is designed to provide additional data to help evaluate the contribution of binimetinib to the combination of binimetinib and encorafenib.

About Melanoma
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates[1],[2]. Only about 20% of people will survive for at least five years following a diagnosis with late-stage disease[1],[2]. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma[1],[3],[4].

About Binimetinib and Encorafenib
MEK and BRAF are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as melanoma, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor and encorafenib is a late-stage small molecule BRAF inhibitor, both of which target key enzymes in this pathway. Binimetinib and encorafenib are being studied in clinical trials in advanced cancer patients, including the Phase 3 BEACON CRC trial with encorafenib in combination with cetuximab with or without binimetinib in patients with BRAF V600E-mutant colorectal cancer.

Binimetinib and encorafenib are investigational medicines and are not currently approved in any country.

Array BioPharma retains exclusive rights to binimetinib and encorafenib in key markets including the U.S., Canada and Israel. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America.

About Pierre Fabre
With a portfolio representing a continuum of activities spanning from prescription drugs and consumer healthcare products to dermo-cosmetics, Pierre Fabre is the 2nd largest dermo-cosmetics laboratory in the world, the 2nd largest private French pharmaceutical group and the market leader in France for products sold over the counter in pharmacies. Its portfolio includes several global brands and franchises among which Eau Thermale Avène - the worldwide dermo-cosmetic market leader - Klorane, Ducray, René Furterer, A-Derma, Galénic, Elancyl, Naturactive, Pierre Fabre Health Care, Pierre Fabre Oral Care, Pierre Fabre Dermatologie and Pierre Fabre Oncologie.

In 2016, Pierre Fabre generated 2,282 million euros in revenues, of which 60% came from its international business and 59% from its dermo-cosmetics division. Pierre Fabre, which has always been headquartered in the South-West of France, counts more than 13,000 employees worldwide, owns subsidiaries and offices in 47 countries and enjoys distribution agreements in over 130 countries. In 2016, Pierre Fabre dedicated ca. 195 million euros to its R&D efforts, split between oncology, central nervous system, consumer healthcare, dermatology and dermo-cosmetics.

Pierre Fabre is 86%-owned by the Pierre Fabre Foundation, a government-recognized public-interest foundation, and secondarily by its own employees through an international employee stock ownership plan.

The independent French certification group AFNOR audited Pierre Fabre for its corporate social responsibility policy at the “exemplary” level, according to the ISO 26000 standard for CSR.

In the case of inconsistencies in the German Spanish and French translations, the English original version shall prevail.

References
[1] Melanoma Skin Cancer. American Cancer Society. Available at: https://www.cancer.org/cancer/melanoma-skin-cancer.html (link is external). Accessed June 2017.
[2] A Snapshot of Melanoma. National Cancer Institute. Available at: https://seer.cancer.gov/statfacts/html/melan.html (link is external). Accessed June 2017.
[3] Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx (link is external). Accessed June 2017.
[4] Klein O, Clements A, Menzies AM, et al. BRAF inhibitor activity in V600R metastatic melanoma. Eur J Cancer. 2013; 49(5):1073-1079.

Contact information

Pierre Fabre
Valérie Roucoules, (33) 1 49 10 83 84
valerie.roucoules@pierre-fabre.com

Om Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Følg saker fra Business Wire

Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.

Siste saker fra Business Wire

IDEMIA and Octo Telematics Reinvent Car Sharing Experience by Adding Facial Recognition to EasyOpen Solution23.2.2018 15:57Pressemelding

IDEMIA, the global leader in Augmented Identity for an increasingly digital world, announces today that it has implemented facial recognition technology on EasyOpen, a solution previously developed with its partner Omoove, a wholly-owned Octo Telematics company, Europe’s leading Shared Mobility technology provider. The digital enrolment process combined with facial recognition technology will securely enroll and authenticate the driver before EasyOpen automatically opens the car. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20180223005506/en/ (Photo: Idemia) You will never rent a car the same way thanks to EasyOpen solution that combines IDEMIA’s expertise in secure service enablement and Omoove’s experience in Shared Mobility platforms and on-board technology. The first version of the solution was launched last year and allows drivers, who have already registered on the application, to use their smartphones as a key to open

SM-Optics Unveils First FLEXSET Chip, Paving the Way to Optical Micro Nodes23.2.2018 14:00Pressemelding

SM-Optics launches FLEXSET, a single chip embedding multiple processing functionalities raising the bar for performances, density and architectural flexibility. The FLEXSET is the heart of the Lightmode product family. FLEXSET OTN switching matrix scales from 300Gbps to 1Tbps and can be addressed by ports spanning from traditional low-speed services like 2Mbps over micro-OTN, to layer2 and layer3 over ODUFlex, 100G over ODU4 and 200G over FlexO. Thanks to its embedded capabilities including multi-technology OAM, packet processing, synchronization and fast protection functions, FLEXSET operates by design at the lowest latency performances and features an Intel Stratix 10 FPGA. Following the launch of micro-OTN, a revolutionary approach to efficiently extend OTN protocol to low speed services, the launch of FLEXSET advances the vision of a highly interconnected metro network and of micro nodes. Revolving around functional block elements, micro nodes collapse in few rack units OTN and pho

Bitcoin Miner HashGains’ Crowdsale to Build Green Cloud Mining Data Centers Receives Excellent Response23.2.2018 13:56Pressemelding

HashGains.com, a leading cryptocurrency mining platform, has launched its crowdsale program to build mega cryptocurrency cloud mining data centers in India and Canada which uses renewable energy like wind and solar as source of energy. “With the growing worries around bitcoin mining causing environmental damage, difficulty levels of mining increasing and returns heading southwards, there was no better opportunity but to build green energy data centers which run on free sources of energy like wind and solar, ensuring handsome mining rewards while taking care of environment,” said Mr Anuj Bairathi, CEO & Founder, HashGains, who is crypto enthusiast himself. HashGains is a growing cloud mining platform with more than 10,000 active customers enjoying mining returns and is expected to reach the mark of 1 million customers by 2020. To handle such a massive growth and ever growing demand of customers, it becomes even more important that mega mining centers are planned which can serve needs of

Stratecast Recognizes CARDINALITY as a “10 to Watch in 2018”23.2.2018 13:07Pressemelding

In their new report, “Digital Transformation Means New Tools for New Business” —part of the Global Operations, Orchestration, Data Analytics, and Monetisation (ODAM) stream—Stratecast recognises CARDINALITY for their new approach towards processing big data to deliver applications such as Customer Experience, Operational Intelligence, Network Analytics, Churn Management and Marketing Intelligence. Stratecast identified that the CARDINALITY Perception Platform brings large amounts of data from multiple CSP sources together in order to address a growing group of data analysis needs from different operational work teams and the wider business. It also does this at ingestion rates and storage levels previously thought not practical. "Using design principals tied to microservices and containerized solution components, the platform is a major advancement in meeting CSP data analysis needs at a price untouchable by previously-defined platforms," said Karl Whitelock, Stratecast director of glo

IBC2018 Welcomes Channel 4’s Keith Underwood as Guest Chair of Content Steering Group23.2.2018 11:03Pressemelding

IBC is thrilled to announce that Keith Underwood, Director of Strategy and Technology at Channel 4, has accepted the role of Guest Chair of the Conference for IBC2018. The position involves acting as the figurehead and brand ambassador for IBC, setting the vision for the programme and increasing awareness and engagement with IBC across both traditional and converging media markets. Keith is the Channel 4 Executive Committee member responsible for strategy and corporate development, broadcast operations, content management, corporate systems and the development of Channel 4’s digital products. His achievements at the public broadcaster include the launch of All 4, Channel 4’s award-winning video on demand service that replaced 4oD in 2015. “The media industry is experiencing profound shifts in consumer behaviour, competitive dynamics, and technological innovation.” Keith Underwood said. “Relentless disruption of established business models presents new opportunities and challenges for p

SES S.A.: Full Year and Fourth Quarter 2017 Results23.2.2018 07:00Pressemelding

SES S.A. announced financial results for the year and three months ended 31 December 2017. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20180222006522/en/ Full Year and Fourth Quarter 2017 Results (Photo: Business Wire) Key financial highlights Reported revenue EUR 2,035.0 million, down 1.6% (-5.2% like-for-like(1)); SES Video -3.6%(1) and SES Networks -1.9%(1) EBITDA margin 65.1% (2016: 70.2% as reported and 66.7% like-for-like(1)) Net profit of EUR 596.1 million (2016: EUR 962.7 million including EUR 495.2 million gain related to O3b consolidation) Board is proposing 2017 dividend per A share of EUR 0.80 (2016: EUR 1.34) Change (%) Change (%) EUR million FY 2017 FY 2016 Reported Like-for-like (1) Q4 2017 Q4 2016 Reported Like-for-like (1) Revenue 2,035.0 2,068.8 -1.6% -5.2% 507.8 578.7 -12.2% -8.7% EBITDA 1,324.2 1,451.5 -8.8% -7.6% 329.6 390.6 -15.6% -12.2% EBITDA margin 65.1% 66.7%(1) 64.9% 67.6%(1) Operating profit (2) 6