Download Combination of Roche medicines Cotellic and Zelboraf approved in

Media Release
Basel, 27 August 2015
Combination of Roche medicines Cotellic and Zelboraf approved in Switzerland
for the treatment of patients with advanced melanoma
New treatment option for patients with difficult-to-treat form of skin cancer has shown improved
treatment outcomes
Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the Swiss licensing and supervisory
authority for therapeutic products (Swissmedic) has approved combination therapy with Cotellic®
(cobimetinib) and Zelboraf® (vemurafenib) for the treatment of patients with advanced melanoma. This
makes Switzerland the first country where this combination therapy is available to patients.
The approval of Zelboraf in 2011 represented a first improvement in therapy for patients with advanced
melanoma. Zelboraf, which selectively inhibits the MAPK signalling mechanism in the cancer cell (the
mutated protein kinase BRAF), was able to prolong overall survival by 4 months (median overall survival
13.6 months) compared to the standard chemotherapy, dacarbazine.1-4
Researchers discovered frequent activation of a further protein kinase, MEK, in BRAF-mutant melanoma.
This discovery led to the development of Cotellic, a MEK inhibitor. Dual inhibition of BRAF and MEK in the
MAPK signalling pathway was the second breakthrough in targeted melanoma therapy. The pivotal coBRIM
study showed that the combination of Cotellic and Zelboraf significantly prolongs the time to disease
progression. Median survival until disease progression was 12.3 months. The coBRIM data were published in
the New England Journal of Medicine in November 2014.
Professori Reinhard Dummer MD, Deputy Head, Department of Dermatology, Zurich University Hospital:
“This combination therapy is the result of systematic further development of BRAF and MEK inhibitor
monotherapy. Combination therapy results in higher response rates and significantly prolonged progressionfree intervals.”
F. Hoffmann-La Roche Ltd
4070 Basel
Switzerland
Group Communications
Roche Group Media Relations
Tel. +41 61 688 88 88
Fax +41 61 688 27 75
www.roche.com
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About melanoma
Dennoch bleibt das maligne Melanom nach wie vor ein ernstes Gesundheitsproblem mit hohem
medizinischem Bedarf und kontinuierlich steigender Inzidenz in den vergangenen 30 Jahren.
Melanoma is less common, but more aggressive than other forms of skin cancer.5,6 BRAF is mutated in
approximately half of melanomas.7 When melanoma is diagnosed early, it is generally a curable disease,8,9
but most people with advanced melanoma have a poor prognosis. More than 232,000 people worldwide are
currently diagnosed with melanoma each year10 and more than 55,000 people worldwide die every year from
melanoma skin cancers.10 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.11
About Zelboraf
Zelboraf was the first prescription treatment for patients with unresectable or metastatic melanoma with
BRAF V600 mutation as detected by a validated test, such as Roche’s cobas 4800 BRAF Mutation Test.
Zelboraf is not indicated for use in patients with wild-type BRAF melanoma.12 It is now approved in more
than 90 countries and has been used to treat more than 11,000 patients worldwide. Zelboraf was codeveloped under a 2006 licence and collaboration agreement between Roche and Plexxikon, now a member
of the Daiichi Sankyo Group.
About Cotellic
Cotellic (GDC-0973, XL518) was discovered by Exelixis Inc. and is being developed in collaboration with
Exelixis. Cotellic is also being investigated in combination with several investigational medicines, including
an immunotherapy, in several tumour types such as non-small cell lung cancer and colorectal cancer.
About the Cotellic and Zelboraf combination
Cotellic is designed to selectively block the activity of MEK,13 one of a series of proteins inside cells that make
up a signalling pathway that helps regulate cell division and survival.14 Cotellic binds to MEK while Zelboraf
binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signalling that can cause
tumours to grow.15,16
About the coBRIM study
The pivotal coBRIM study is an international, randomised, double-blind, placebo-controlled, Phase III study
evaluating the safety and efficacy of the combination therapy. A total of 495 patients with unresectable,
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locally advanced or metastatic melanoma with a BRAF V600 mutation were randomised to receive Zelboraf
once daily at the approved dosage and either Cotellic or a placebo for 3 weeks followed by one week off
Cotellic/placebo. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of
consent. Investigator-assessed progression-free survival (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 measures.17
The coBRIM results showed that patients with previously untreated BRAF V600 mutation-positive advanced
melanoma live a median of more than a year (12.3 months) without progression of their disease
(progression-free survival, PFS) on combination therapy with Cotellic and Zelboraf, and only 7.2 months on
Zelboraf monotherapy.18
Patients treated with Cotellic and Zelboraf also responded better to treatment than those given Zelboraf
alone. The objective response rate (ORR) of the Cotellic and Zelboraf combination was 70 percent (compared
to 50 percent for monotherapy).18 With further follow-up, the complete response rate increased from 10
percent to 15 percent with the combination as some patients who had a partial response achieved a complete
response after more than one year of treatment. The safety profile of Cotellic and Zelboraf was consistent
with safety data previously reported from the Phase Ib BRIM7 study. The most common adverse events in
the combination arm were diarrhea, rash, nausea, fever, sun sensitivity, liver lab abnormalities, elevated
creatine phosphokinase (CPK, an enzyme released by muscles) and vomiting.
About Roche in skin cancer
Roche has been studying new treatments for skin cancer for nearly 20 years. In the last five years, we have
brought two new medicines to people with potentially disfiguring or deadly skin cancers. Our two first-inclass medicines, Erivedge and Zelboraf, have significantly improved treatment options for advanced stages of
the most common and most serious skin cancers. Zelboraf was the first targeted oral medicine to be
approved with a companion diagnostic. Erivedge is the first hedgehog pathway inhibitor and first medicine
ever approved for advanced forms of the most common skin cancer, basal cell carcinoma. Roche is
continuing to study Zelboraf, Erivedge and Cotellic as monotherapies and in combination with other
investigational medicines, such as cancer immunotherapies, in several cancer types and diseases.
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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. Twentynine medicines developed by Roche are included in the World Health Organisation Model Lists of Essential
Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.
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 Office
Telephone: +41 61 688 88 88 / E-mail: [email protected]
- Nicolas Dunant (Head)
- Ulrike Engels-Lange
- Nina Schwab-Hautzinger
- Štěpán Kráčala
- Nicole Rüppel
- Claudia Schmitt
References
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in patients with metastatic melanoma. J Clin Oncol 1999;17:2745-51.
2. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of
patients with advanced metastatic malignant melanoma. J Clin Oncol 2000;18:158-66.
3. Avril MF, Aamdal S, Grob JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a
phase III study. J Clin Oncol 2004;22:1118-25.
4. Bedikian AY, Millward M, Pehamberger H, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients
with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006; 24:4738-45.
5. Algazi AP, et al. Treatment of cutaneous melanoma: current approaches and future prospects. Cancer Manag Res. 2010;2:197-211.
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6. Finn L, et al. Therapy for metastatic melanoma: the past, present, and future. BMC Med. 2012;10:23.
7. Ascierto PA, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012;10:85.
8. Leong SP. Future perspectives on malignant melanoma. Surg Clin North Am. 2003;83:453-6.
9. Creagan ET. Malignant melanoma: an emerging and preventable medical catastrophe. Mayo Clin Proc. 1997;72:570-4.
10. 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 April 2015.
11. Bataille V. Risk factors for melanoma development. Expert Rev Dermatol. 2009;4:533-9.
12. Zelboraf Summary of Product Characteristics, August 2014. Available at: http://www.ema.europa.eu Last accessed April 2015.
13. Johnston S. XL518, a potent, selective, orally bioavailable MEK1 inhibitor, downregulates the Ras/Raf/MEK/ERK pathway in vivo,
resulting in tumor growth inhibition and regression in preclinical models. Poster presented at: AACR-NCI-EORTC Symposium on
Molecular Targets and Cancer Therapeutics; October 22, 2007; San Francisco, CA. Abstract C209.
14. Khavari TA, et al. Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia. Cell Cycle. 2007;6:2928-31
15. 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.
16. Haferkamp S, et al. Vemurafenib induces senescence features in melanoma cells. J Invest Dermatol. 2013;133:1601-9.
17. Larkin J, et al. Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma. N Engl J Med. 2014;371(20):1867-76.
18. 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.
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Translator’s note: I have left in the paragraph break here and the endnote at the end of the previous paragraph. The
intention was unclear in the source text.
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