New targeted therapy for treatment of serious form of skin cancer approved in Canada

Cotellic^TM in combination with Zelboraf^® designed to inhibit cancer growth in metastatic melanoma

MISSISSAUGA, ON, Feb. 25, 2016 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) announced today that Health Canada has approved Cotellic (cobimetinib) in combination with Zelboraf (vemurafenib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Melanoma – a type of skin cancer that develops in the cells (melanocytes) that produce the pigment that gives skin its colour¹ – impacts close to 7,000 Canadians each year, and approximately 50 per cent of all cases are BRAF-positive.^2,3 More than 1,150 people in Canada died last year as a result of the disease, making it the most serious type of skin cancer today.^4,5

The new combination therapy offers physicians a treatment option that builds on their experience with Zelboraf, another Roche medicine approved for the treatment of and shown to improve survival for people with BRAF V600 mutation-specific unresectable or metastatic melanoma.⁶ When used in combination, Cotellic (a MEK inhibitor) and Zelboraf (a BRAF inhibitor) has been observed to reduce cancer cell growth longer than with Zelboraf alone.⁷

"Providing melanoma patients in Canada with the treatment option of Cotellic and Zelboraf as a combination therapy will help delay disease progression and lead to significantly better outcomes compared to those treated with Zelboraf alone," said Dr. Winson Cheung, Medical Oncologist at the British Columbia Cancer Agency and Associate Professor at the University of British Columbia, Department of Medicine. "This new targeted approach gives physicians another option when treating cases of melanoma, helping patients live longer without their disease worsening. It's encouraging to see research and innovation in this space as there continues to be a significant unmet need within this patient population."

Melanoma is one of the fastest growing cancers worldwide and when diagnosed early, it is generally a curable disease.⁸ However, many Canadians living with advanced melanoma have a relatively poor prognosis⁹ and have limited treatment options especially in advanced or complex cases.¹⁰

"Personalized treatment is a significant development in cancer care, particularly when dealing with a disease as complex as melanoma," says Kathy Barnard, founder of Save Your Skin Foundation and melanoma survivor. "As someone who has tested positive for the BRAF mutation, I understand first-hand the importance of having targeted treatment options to choose from and am thrilled to see the approval of the combination of Cotellic and Zelboraf for other Canadians who can benefit from it."

"Over the past few years, we've witnessed a dramatic change in the melanoma treatment landscape with new and exciting innovations for patients," says Annette Cyr, chair of Melanoma Network of Canada and melanoma survivor. "Health Canada's approval of Cotellic in combination with Zelboraf brings new hope for Canadians living with metastatic melanoma by providing more treatment options to choose from to make a choice that is right for them."

Cotellic is also approved in the European Union and Switzerland for the treatment of people with BRAF V600 mutation-positive advanced melanoma. In the United States, the combination is approved for the treatment of people with BRAF V600E and V600K mutation-positive advanced melanoma.

About the Health Canada Approval
The Health Canada approval of Cotellic is based on results of the pivotal Phase III coBRIM study, which demonstrated that Cotellic in combination with Zelboraf helped people with previously untreated BRAF V600 mutation-positive advanced melanoma live longer without their disease worsening (median progression-free survival of 9.9 months, compared to 6.2 months with Zelboraf alone; hazard ratio=0.51, 95 percent confidence interval 0.39-0.68, p-value < 0.0001). The objective response rate was also higher for the combination arm compared to Zelboraf alone (67.6 vs. 44.8 percent, p-value < 0.0001).¹¹

The most common adverse events (≥ 20 percent) that occurred with greater frequency in the Cotellic in combination with Zelboraf arm were diarrhea, rash, nausea, blood CPK increased, photosensitivity reaction, pyrexia, ALT increased, AST increased, and vomiting.^12,13

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.¹⁴

In the study, 495 patients, including 18 Canadian 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 1-21.¹⁵ Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent.¹⁶ The primary endpoint of the trial was investigator-assessed progression free survival (PFS). Secondary endpoints included PFS by independent review committee, objective response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures.¹⁷

About Cotellic in combination with 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. Zelboraf was the first personalized medicine approved for the treatment of 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.¹⁸

Cotellic is designed to selectively inhibit the activity of MEK, one of a series of proteins inside cells that make up the MAPK signaling pathway that helps regulate cell division and survival. In the majority of patients, resistance to BRAF-inhibitor monotherapy will eventually occur through re-activation of the MAPK pathway via MEK. Cotellic was developed to overcome resistance to BRAF-inhibition and prevent re-activation of the pathway. Cotellic binds to MEK, while Zelboraf binds to mutant BRAF, to interrupt abnormal signalling that can cause tumours to grow. A patient's healthcare provider will 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.¹⁹ Cotellic was discovered by Exelixis Inc. and is being developed by Roche in collaboration with Exelixis.

About Melanoma
Melanoma is less common, but more aggressive and is a serious form of skin cancer.^20,21 A V600 mutation of the BRAF protein occurs in approximately half of melanomas and should therefore be tested to identify the best treatment option.²² When melanoma is diagnosed early, it is generally a curable disease,²³ but most people with advanced melanoma have a poor prognosis.²⁴

Incidence of melanoma in both Canadian men and women has been increasing over the past 25 years, faster than that of any other cancer.²⁵ In their lifetime, one in 59 men and one in 73 women in Canada are expected to develop melanoma.²⁶ Though treatment options have expanded significantly in recent years,²⁷ there continues to be a largely unmet need for targeted approaches and personalized treatment for melanoma patients in Canada.²⁸

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, bringing about medical advances and setting new standards of care. Zelboraf and Erivedge^®, therapies for two of the most difficult-to-treat skin cancers, metastatic melanoma and advanced basal cell carcinoma, have been used to treat more than 28,000 patients worldwide. 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 personalized healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life, and survival of patients. Founded in 1886, Roche has been making important contributions to global health for more than a century. Twenty-eight medicines developed by Roche are included in the World Health Organization 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.

Roche Canada was founded in 1931. The company employs approximately 900 people across the country, with its pharmaceuticals head office located in Mississauga, Ontario, and diagnostics division based in Laval, Quebec. Roche Canada is actively involved in local communities, investing in charitable organizations and partnering with healthcare institutions across the country. For more information, visit www.rochecanada.com.  

All trademarks used or mentioned are legally protected.

For more information, please contact:

Ashley Iyer-Dhillon
Roche Canada
905-542-5907
[email protected]

Charlotte Macgregor
Edelman Public Relations
647-464-2995
[email protected]

References

¹ Mayo Clinic. "Definition: Melanoma." Available online at: http://www.mayoclinic.org/diseasesconditions/melanoma/basics/definition/con-20026009. Last accessed on January 20, 2016

² Canadian Cancer Society, "Melanoma statistics." Available online at: http://www.cancer.ca/en/cancer-information/cancer-type/skin-melanoma/statistics/?region=on. Last accessed on January 25, 2016

³ Melanoma International Foundation. "Melanoma Treatment: Stage IV." Available online at: http://melanomainternational.org/melanoma-facts/melanoma-treatment-stage-iv/#.VnMjlPkrLcs.  Last accessed on December 17, 2015

⁴ Canadian Cancer Society, "Melanoma statistics." Available online at: http://www.cancer.ca/en/cancer-information/cancer-type/skin-melanoma/statistics/?region=on. Last accessed on January 25, 2016

⁵ Mayo Clinic. "Definition: Melanoma." Available online at: http://www.mayoclinic.org/diseasesconditions/melanoma/basics/definition/con-20026009. Last accessed on January 20, 2016

⁶ First and Only Personalized Treatment for Deadliest Form of Skin Cancer Approved by Health Canada. News Release. February 16, 2012. Available online at: http://www.newswire.ca/news-releases/first-and-only-personalized-treatment-for-deadliest-form-of-skin-cancer-approved-by-health-canada-509660371.html. Last accessed on December 22 2015

⁷ Larkin JM, et al. Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma. N Engl J Med. 2014; 371(20):1867-76. Available online at: http://www.nejm.org/doi/full/10.1056/NEJMoa1408868. Last accessed on November 30, 2015

⁸ Melanoma Network of Canada. "Fact Sheet - Melanoma." Available online at: https://melanomanetwork.ca/pdfs/FACT%20SHEET%20Melanoma.pdf. Last accessed on November 30, 2015

⁹ Melanoma Network of Canada. "Fact Sheet - Melanoma." Available online at: https://melanomanetwork.ca/pdfs/FACT%20SHEET%20Melanoma.pdf. Last accessed on November 30, 2015

¹⁰ Sosman J, et al. Survival in BRAF V600-Mutant Advanced Melanoma Treated with Vemurafenib. N Engl J Med 2012; 366:707-714. Available online at: http://www.nejm.org/doi/full/10.1056/NEJMoa1112302. Last accessed on December 22, 2015

¹¹ Cotellic Product Monograph

¹² Cotellic Product Monograph

¹³ Ibid.

¹⁴ Larkin JM, et al. Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma. N Engl J Med. 2014; 371(20): 1867-76. Available online at: http://www.nejm.org/doi/full/10.1056/NEJMoa1408868. Last accessed on November 30, 2015

¹⁵ Ibid.

¹⁶ Ibid.

¹⁷ Ibid.

¹⁸ Zelboraf Product Monograph

¹⁹ Larkin JM, et al. Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma. N Engl J Med. 2014; 371(20):1867-76. Available online at: http://www.nejm.org/doi/full/10.1056/NEJMoa1408868. Last accessed on November 30, 2015

²⁰ Algazi AP, et al. Treatment of cutaneous melanoma: current approaches and future prospects. Cancer Manag Res. 2010; 2:197-211. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/21188111. Last accessed on November 30, 2015

²¹ Finn L, et al. Therapy for metastatic melanoma: the past, present, and future. BMC Med. 2012; 10:23. Available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308914/. Last accessed on November 30, 2015

²² Ascierto PA, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012; 10:85. Available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391993/. Last accessed on November 30, 2015

²³ Leong SP. Future perspectives on malignant melanoma. Surg Clin North Am. 2003; 83:453-6. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/12744619. Last accessed on November 30, 2015

²⁴ Finn L, et al. Therapy for metastatic melanoma: the past, present, and future. BMC Med. 2012; 10:23. Available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308914/. Last accessed on November 30, 2015

²⁵ Canadian Cancer Society. "Melanoma: deadliest type of skin cancer is on the rise." Available online at: https://www.cancer.ca/en/about-us/for-media/media-releases/national/2014/2014-canadian-cancer-statistics/?region=on. Last accessed on November 30, 2015

²⁶ Ibid.

²⁷ Melanoma Network of Canada. "Drug or Treatment Therapies." Available online at: https://www.melanomanetwork.ca/drugtherapies/. Last accessed on November 30, 2015

²⁸ Sosman J, et al. Survival in BRAF V600-Mutant Advanced Melanoma Treated with Vemurafenib. N Engl J Med 2012; 366:707-714. Available online at: http://www.nejm.org/doi/full/10.1056/NEJMoa1112302. Last accessed on December 22, 2015

SOURCE Roche Canada