– Positive CHMP opinion is based on Phase 3 COLUMBUS trial which demonstrated nearly 15 months median progression-free survival and over 30 months median overall survival –

– U.S. FDA recently approved BRAFTOVI + MEKTOVI for advanced BRAF-mutant melanoma –

BOULDER, CO, USA I July 27, 2018 I Array BioPharma Inc. (NASDAQ: ARRY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of BRAFTOVIin combination with MEKTOVI® for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation. The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). The final EC decision, expected by the end of September, will be applicable to all 28 EU member states, as well as Liechtenstein, Iceland and Norway.

“Following the recent U.S. FDA approval of BRAFTOVI + MEKTOVI for advanced BRAF-mutant melanoma, we are pleased to move one step closer to European approval,” said Ron Squarer, Chief Executive Officer. “We are proud that the combination of BRAFTOVI + MEKTOVI represents a new standard of care for BRAF-mutant melanoma patients in critical need of additional treatment options.”

The positive CHMP opinion is based on results from the Phase 3 COLUMBUS trial, which demonstrated that the combination BRAFTOVI + MEKTOVI achieved a median progression-free survival (mPFS) of nearly 15 months [14.9 months versus vemurafenib monotherapy at 7.3 months; hazard ratio (HR) 0.54 (95% CI, 0.41–0.71), p<0.0001].  

In June 2018, Array also announced updated results from the COLUMBUS trial, which demonstrated that BRAFTOVI + MEKTOVI was the first targeted therapy to achieve over 30 months overall survival (OS) in a Phase 3 trial and reduced the risk of death compared to treatment with vemurafenib [HR (0.61), (95% CI 0.47-0.79, p <0.0001]. Median OS was 33.6 months for patients treated with the combination, compared to 16.9 months for patients treated with vemurafenib as a monotherapy.

The most common grade 3-4 adverse events seen in more than 5% of patients were increased gamma-glutamyltransferase (9%), increased blood creatine phosphokinase (7%) and hypertension (6%).  

In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma.

Only 5% of patients who received BRAFTOVI + MEKTOVI discontinued treatment due to adverse reactions. The most common adverse reactions (≥25%) in patients receiving BRAFTOVI + MEKTOVI were fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia.

Detailed recommendations for the use of these products will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official EU languages after the marketing authorization has been granted by the EC. Pierre Fabre has exclusive rights to commercialize both products in Europe, Asia and Latin America.

About BRAF-mutant Metastatic Melanoma

Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumors. Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1,2] There are a variety of gene mutations that can lead to metastatic melanoma. The most common genetic mutation in metastatic melanoma is BRAF. 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. [1-5]

About BRAFTOVI + MEKTOVI

BRAFTOVI is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer, thyroid and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma.

Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America.

BRAFTOVI and MEKTOVI are not approved outside of the United States. The European Medicines Agency (EMA), the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA) are currently reviewing the Marketing Authorization Applications, and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan is currently reviewing the Manufacturing and Marketing Approval Applications for BRAFTOVI and MEKTOVI.

About COLUMBUS

The COLUMBUS trial (NCT01909453) is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of BRAFTOVI (encorafenib) in combination with MEKTOVI (binimetinib) compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. All secondary efficacy analyses, including overall survival, are descriptive in nature. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial.

Indications and Usage

BRAFTOVI™ (encorafenib) and MEKTOVI® (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.

About Array BioPharma

Array BioPharma Inc. is a fully-integrated, biopharmaceutical company focused on the discovery, development and commercialization of safe and effective targeted small molecule drugs to treat patients afflicted with cancer and other conditions. Array markets in the United States BRAFTOVITM capsules in combination with MEKTOVI® tablets for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation. Array’s lead clinical programs, encorafenib and binimetinib, are being investigated in over 30 clinical trials across a number of solid tumor indications, including a Phase 3 trial in BRAF-mutant colorectal cancer. Array’s pipeline includes several additional advanced programs including selumetinib (partnered with AstraZeneca), larotrectinib (partnered with Loxo Oncology), ipatasertib (partnered with Genentech), tucatinib (partnered with Seattle Genetics) and ARRY-797 (being developed by Yarra Therapeutics, a wholly-owned subsidiary of Array), all of which are currently in registration trials. Ganovo® (danoprevir, partnered with Roche) was recently approved in China for the treatment of viral hepatitis C. For more information on Array, please visit www.arraybiopharma.com or follow @arraybiopharma on Twitter and LinkedIn.

References 

[1] Melanoma Skin Cancer. American Cancer Society. Available at: https://www.cancer.org/cancer/melanoma-skin-cancer.html. Accessed January 2018. 

[2] A Snapshot of Melanoma. National Cancer Institute. Available at: https://seer.cancer.gov/statfacts/html/melan.html. Accessed January 2018. 

[3] Globocan 2012:  Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed January 2018. 

[4] Klein O, et al. Eur J Cancer, 2013.  

[5] American Cancer Society. What Causes Melanoma Skin Cancer? 2016. https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/what-causes.html. Accessed April 11, 2018.

[6] BRAFTOVI™ (encorafenib) Prescribing Information. Array BioPharma Inc., June 2018

[7] MEKTOVI® (binimetinib) Prescribing Information. Array BioPharma Inc., June 2018

SOURCE: Array BioPharma