Download (vemurafenib) in advanced melanoma

Media Release
Basel, 11 November 2015
FDA approves Roche’s Cotellic (cobimetinib) in combination with Zelboraf
(vemurafenib) in advanced melanoma
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FDA approval underscores the important role of targeted medicines to help people with BRAF V600
mutation-positive advanced melanoma
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Pivotal coBRIM study showed the combination improved progression-free and overall survival
compared to Zelboraf alone
Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food and Drug Administration
(FDA) approved Cotellic (cobimetinib) for the treatment of people with BRAF V600E or V600K mutationpositive unresectable or metastatic melanoma in combination with Zelboraf (vemurafenib). Cotellic and
Zelboraf are not used to treat melanoma with a normal BRAF gene. Cotellic is Roche’s seventh new medicine
approved by the FDA in the past five years.
“When used in combination, Cotellic and Zelboraf help delay disease progression and help people live
significantly longer than with Zelboraf alone,” said Sandra Horning, M.D., Chief Medical Officer and Head
of Global Product Development. “With this approval, people with this type of deadly and aggressive skin
cancer now have a new targeted option.”
Today’s FDA approval is based on results from the Phase III coBRIM study, which showed Cotellic plus
Zelboraf reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in
people who received the combination [HR=0.56, 95 percent CI (0.45-0.70); p<0.001], with a median PFS of
12.3 months for Cotellic plus Zelboraf compared to 7.2 months with Zelboraf alone1. An interim analysis also
showed the combination of Cotellic and Zelboraf helped people live significantly longer (overall survival; OS)
than Zelboraf alone (HR=0.63, 95 percent CI 0.47-0.85; p=0.0019). The objective response rate (tumor
shrinkage) was higher with Cotellic plus Zelboraf compared to Zelboraf alone (70 vs. 50 percent; p<0.001), as
was the complete response rate (complete tumor shrinkage, 16 vs. 11 percent) 1.
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Possible serious side effects with Cotellic include risk of skin cancers, increased risk of bleeding, heart
problems that can lead to inadequate pumping of the blood by the heart, rash, eye problems, abnormal liver
test or liver injury, increased levels of an enzyme in the blood, and photosensitivity. The most common side
effects of Cotellic include diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting. Cotellic can also
cause changes in blood test results.
The final overall survival analysis from the coBRIM study will be presented at the Society for Melanoma
Research 2015 International Congress (SMR) held in San Francisco, California from November 18-21.
In September, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines
Agency (EMA) issued a positive opinion for Roche’s marketing authorization application for Cotellic in the
European Union. A decision from the European Commission is expected before the end of 2015. Cotellic was
approved in Switzerland by Swissmedic in August 2015.
About the coBRIM study
CoBRIM is an international, randomized, double-blind, placebo-controlled Phase III study evaluating the
safety and efficacy of 60 mg once daily of Cotellic plus 960 mg twice daily of Zelboraf compared to 960 mg
twice daily of Zelboraf plus placebo. In the study, 495 patients with BRAF V600 mutation-positive
unresectable locally advanced or metastatic melanoma (detected by the cobas 4800 BRAF Mutation Test) and
previously untreated for advanced disease were randomized to receive Zelboraf every day on a 28-day cycle
plus either Cotellic or placebo on days 1-21. Treatment was continued until disease progression,
unacceptable toxicity or withdrawal of consent. Investigator-assessed PFS is the primary endpoint. Secondary
endpoints include PFS by independent review committee, objective response rate, overall survival, duration
of response and other safety, pharmacokinetic and quality of life measures2.
About Cotellic plus Zelboraf
Cotellic and Zelboraf are prescription medicines used in combination to treat melanoma that has spread to
other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal “BRAF”
gene. Found in approximately half of melanomas3, mutated BRAF causes abnormal signaling inside certain
cancer cells leading to tumor growth4,5. Zelboraf is designed to inhibit some mutated forms of BRAF and
Cotellic is designed to inhibit some forms of MEK. Both BRAF and MEK are proteins in a cell signaling
pathway that help control cell growth and survival6. When used in combination, Cotellic and Zelboraf are
thought to reduce cancer cell growth longer than with Zelboraf alone. A patient’s healthcare provider will
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perform a test to make sure Cotellic and Zelboraf are right for the patient. It is not known if Cotellic and
Zelboraf are safe and effective in children under 18 years of age.
About melanoma
Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer.,7,8 BRAF is
mutated in approximately half of melanomas.3 When melanoma is diagnosed early, it is generally a curable
disease,9,10 but most people with advanced melanoma have a poor prognosis.8 More than 232,000 people
worldwide are currently diagnosed with melanoma each year.11 In recent years, there have been significant
advances in treatment for metastatic melanoma and people with the disease have more options. However, it
continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the
past 30 years.12
Roche in skin cancer
The Roche Group is the world’s leading provider of cancer care products, including anti-cancer treatments,
supportive care products and diagnostics. In the area of skin cancer, Roche scientists have been studying
treatments for nearly 20 years. More than 28,000 patients having been treated worldwide, bringing about
medical breakthroughs and new standards of care that include Zelboraf and Erivedge, treatments for two of
the most difficult-to-treat skin cancers, metastatic melanoma and basal cell carcinoma. Roche is continuing
to study skin cancer medicines as monotherapies and in combination with other investigational medicines,
such as cancer immunotherapies, in several cancer types and diseases.
About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in
pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines
in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in
in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s
personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in
the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions
to global health for more than a century. Twenty-nine medicines developed by Roche are included in the World
Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and
chemotherapy.
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In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted
sales of 47.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group.
Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit
www.roche.com.
All trademarks used or mentioned in this release are protected by law.
Roche Group Media Relations
Phone: +41 -61 688 8888 / e-mail: [email protected]
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Nicolas Dunant (Head)
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Ulrike Engels-Lange
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Claudia Schmitt
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Nicole Rüppel
Additional information
Roche in Oncology: www.roche.com/media/media_backgrounder/media_oncology.htm
References
1. Larkin J et al., Update of progression-free survival and correlative biomarker analysis from coBRIM: cobimetinib plus
vemurafenib in advanced BRAF-mutated melanoma. Abstract presented at ASCO, Chicago, IL, USA, 29 May – 2 June 2015;
abstract #9006.
2. Larkin JM, et al. Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma. N Engl J Med. 2014;371(20):1867-76.
3. Ascierto PA, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012;10:85.
4. Safaee Ardekani G, et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and
meta-analysis. PLoS One. 2012;7(10):e47054.
5. Haferkamp S, et al. Vemurafenib induces senescence features in melanoma cells. J Invest Dermatol. 2013;133:1601-9.
6. Khavari TA, et al. Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia. Cell Cycle. 2007;6:2928-31.
7. Algazi AP, et al. Treatment of cutaneous melanoma: current approaches and future prospects. Cancer Manag Res. 2010;2:197211.
8. Finn L, et al. Therapy for metastatic melanoma: the past, present, and future. BMC Med. 2012;10:23.
9. Leong SP. Future perspectives on malignant melanoma. Surg Clin North Am. 2003;83:453-6.
10. Creagan ET. Malignant melanoma: an emerging and preventable medical catastrophe. Mayo Clin Proc. 1997;72:570-4.
11. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012
v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for
Research on Cancer; 2013. Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx; Last accessed September
2015.
12. Bataille V. Risk factors for melanoma development. Expert Rev Dermatol. 2009;4:533-9.
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