European Medicines Agency To Start the Review of The Marketing Authorization Applications for Encorafenib and Binimetinib For the Treatment Of BRAF-Mutant Advanced Melanoma
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.
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.
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates,. Only about 20% of people will survive for at least five years following a diagnosis with late-stage disease,. 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,,.
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.
 Melanoma Skin Cancer. American Cancer Society. Available at: https://www.cancer.org/cancer/melanoma-skin-cancer.html (link is external). Accessed June 2017.
 A Snapshot of Melanoma. National Cancer Institute. Available at: https://seer.cancer.gov/statfacts/html/melan.html (link is external). Accessed June 2017.
 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.
 Klein O, Clements A, Menzies AM, et al. BRAF inhibitor activity in V600R metastatic melanoma. Eur J Cancer. 2013; 49(5):1073-1079.
Valérie Roucoules, (33) 1 49 10 83 84
Om Business Wire
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
CHTF 2017 Gathers Enterprises From 27 “One Belt, One Road” Countries22.11.2017 07:00 | Pressemelding
Echoing the “One Belt, One Road” initiative, the 19th China Hi-Tech Fair (CHTF 2017) which concluded on November 21, invited over 30 countries and international organizations, including Argentina, Belgium, The Czech Republic, Germany, Greece, Iran, Lithuania, Pakistan, Poland, Russia, Sweden, UK and EU, to exhibit jointly at the “One Belt, One Road” Pavilion, setting a new record in its history. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20171121005458/en/ The Bavarian delegation sent 11 enterprises including leading hi-tech players such as Pfaff-Silberblau, a pioneer in mechanical drive and hoisting parts and solutions under Columbus McKinnon Engineered Products, as well as four newcomers including the most innovative startup NavVis. The Korean delegation once again broke its record in terms of the number
ION Investment Group Recapitalizes Dealogic, a Carlyle Portfolio Company22.11.2017 06:59 | Pressemelding
ION Investment Group ("ION") and The Carlyle Group announced a recapitalization of Dealogic, a global provider of data and analytics for the capital markets, in which ION is acquiring a controlling stake in the company and Carlyle and management are retaining significant ownership. The transaction is subject to customary approvals and is expected to close in the fourth quarter of 2017. Headquartered in New York and London with offices in Hong Kong, Budapest, Tokyo, Mumbai, Sydney, Beijing, Singapore, and São Paulo, Dealogic provides solutions to more than 800 clients globally including each of the world’s top 50 investment banks. Cam Dyer, Managing Director and Co-head of Carlyle’s global Technology, Media and Telecom group, said, “Our partnership with Tom, his team and our co-investors, including FiveW Capital, Euromoney and the company’s other co-founders, has further esta
First Tom Ford Beauty Store Opens in London21.11.2017 20:01 | Pressemelding
Debuting on November 20, 2017, the first TOM FORD beauty standalone store is the ultimate in luxury beauté, expressed through Tom Ford’s singular vision. Located in historic Covent Garden (3 The Market Building) this store is a pivotal moment in the evolution of the brand. The new design of light and layered grey glass sculpture creates a visually arresting play on objects and space while highlighting his collection of makeup, skincare and fragrance for women and men. Tom Ford’s inimitable touch reverberates in every dimension of the store, beginning with the LED screens lining the façade with the latest campaigns. Halos of light and floating white marble slabs showcase the exquisite design of his products, fully immersing you in the convergence of glamour and technology for the most luxurious retail environment. A complete vision of the breadth of the world of TOM FORD
Brazil Hospitality Group (BHG) Starts Partnership with AccorHotels21.11.2017 18:29 | Pressemelding
Brazil Hospitality Group (BHG) announces today the beginning of its partnership with AccorHotels, which will manage 17 of BHG’s owned hotels. AccorHotels also acquired LEBSPE Ltda from BHG, a company that manages The Capital São Paulo Itaim and Grand Plaza São Paulo Jardins hotels, in São Paulo; Soft Inn São Luis, in Maranhão; and Presidente Uberlândia Hotel, in Minas Gerais. BHG, the largest owner of hotel assets in Brazil, with more than R$ 1.2 billion in properties, will invest approximately R$ 300 million, in the next four years, in the renovation and repositioning of the 17 hotels that will progressively receive the flags of AccorHotels. BHG has also started a total renovation and repositioning of Marina Palace Leblon, in Rio de Janeiro which is not part of the Accor transaction. The renovation projects will be designed by renowned architects. BHG is excited to add to i
ThreatMetrix Winter ’18 Release Increases Speed, Accuracy and Reliability of Digital Identity Assessments21.11.2017 18:24 | Pressemelding
ThreatMetrix ®, The Digital Identity Company® today announced the Winter ’18 Release, which features new industry-level classifications and performance enhancements which bolster ThreatMetrix real-time solutions. Improving Performance of the Digital Identity Network ThreatMetrix has invested in significant upgrades across the Digital Identity Network®: SmartID has been re-architected to provide superior and faster cookie-less device recognition. This delivers improved global matching across the 4.5 billion unique devices on the ThreatMetrix Network. Improved responsiveness in the ThreatMetrix Decision Management Portal, supported by a new data warehouse and acceleration layer for reporting. Infrastructure investments across multiple global data centers to support resilience and peak thr
Porta Solutions Has Been Awarded as Excellence of the Year Innovation & Leadership for the Flexible Production at Le Fonti Awards 201721.11.2017 17:04 | Pressemelding
Maurizio Porta, Porta Solutions’CEO triumphed at the 32th edition of the IAIR Awards. The Award Ceremony, held at the at London Stock Exchange on the 20th of October 2017, crowned him the Excellence of the Year, Innovation & Leadership, for the Flexible Production. For being an Italian excellence since 1958, innovative leader in the sector of productive flexibility in the manufacturing world. In particular to be able to aim continually and strategically on innovation and customization to ensure the best performance and highest quality. “Flexible Production: produce what you sell, no stock, no stress, more cash" says Maurizio Porta. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20171121005803/en/ Porta Solutions was awarded at the Le Fonti Awards (Photo: Business Wire) Today, the
I vårt presserom finner du alle våre siste saker, kontaktpersoner, bilder, dokumenter og annen relevant informasjon om oss.Besøk vårt presserom