Lynparza® (olaparib) Receives Health Canada Approval for the Treatment of BRCA or ATM Gene-Mutated Metastatic Castration-Resistant Prostate Cancer

Lynparza is the first targeted treatment approved in biomarker-selected prostate cancer validated by a Phase III trial¹ 

MISSISSAUGA, ON, Nov. 25, 2020 /CNW/ - On August 21, 2020, Health Canada approved Lynparza® (olaparib), for the treatment of adult patients with deleterious or suspected deleterious germline and/or somatic BRCA or ATM-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with a new hormonal agent (NHA). BRCA1/2 or ATM gene mutation must be confirmed before Lynparza treatment is initiated.

The Notice of Compliance was granted under priority review and marks the first Health Canada approval of a PARP inhibitor in prostate cancer. Lynparza is the first biomarker-selected targeted treatment option approved in Canada, based on the Phase III PROfound trial of men with Homologous Recombination Repair mutated (HRRm) mCRPC.¹ This approval follows previous indications in ovarian, breast and pancreatic cancers.

"Sadly, the risk of developing prostate cancer is significantly higher for carriers of the BRCA or ATM-gene mutation, which affects roughly 10 per cent of men living with mCRPC," said Dr. Kim Chi,  Medical Oncologist and Professor of Medicine at the University of British Columbia. "This new approval offers patients a much-needed new treatment option, and also reinforces the importance of BRCA and ATM testing."  

Prostate cancer is the most common cancer among Canadian men, and the third leading cause of cancer deaths amongst this demographic.² On average, 64 Canadian men are diagnosed with prostate cancer and 11 men die from it every day.² Germline and somatic mutations in HRR genes, which include BRCA1/2 and ATM, are associated with potentially more aggressive prostate cancers and poor prognosis, demonstrating the importance of biomarker testing.^3,4,5,6 

Currently, mCRPC remains an incurable disease, and despite advancements in available therapies, the 5 year survival rate for men with metastatic prostate cancer is only 28 per cent.^7,8 

"We are thrilled to hear about this new indication for patients with BRCA or ATM-mutated mCRPC," said Jackie Manthorne, President & CEO, Canadian Cancer Survivor Network. "This aggressive form of prostate cancer can have a devastating impact on patients and families, but this new treatment option is providing much-needed hope for better outcomes." 

The Health Canada approval of Lynparza for BRCA or ATM gene-mutated mCRPC was based on data from Cohort A of the global Phase III PROfound trial. The PROfound trial evaluated the safety and efficacy of Lynparza versus investigator's choice of a new hormonal agent (abiraterone or enzalutamide) in men with mCRPC who have a mutation in at least one of 15 qualifying HRR genes. Cohort A of the PROfound trial, which included men with BRCA1, BRCA2, and/or ATM gene alterations, showed that Lynparza significantly reduced the risk of radiographic disease progression or death  and significantly delayed time to pain progression versus the investigator's choice of a new hormonal agent.^9a At the time of rPFS analysis, the interim OS data for Cohort A also indicated a trend in OS benefits in Lynparza treated patients.^9a 

The safety and tolerability profile seen with Lynparza in the PROfound study was consistent with that reported in previous trials, except for the addition of venous thromboembolic events (VTE). In the PROfound trial, VTE including pulmonary embolism, occurred in 7% of patients with mCRPC who received Lynparza plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving Investigator's Choice of NHA.⁹ Patients receiving Lynparza and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Based on the available clinical trial data, a causal association between Lynparza treatment and VTE including pulmonary embolism has not been established. Patients should be monitored for signs and symptoms of venous thrombosis and pulmonary embolism and treated as medically appropriate, which may include long-term anticoagulation as clinically indicated.

Approximately 32 patients from 12 Canadian centres have participated in the PROfound trial to date.¹⁰ Participation in Canadian clinical trials will continue on an ongoing basis.

About Prostate Cancer 
Prostate cancer is the most prevalent cancer in Canadian men, with an estimated 23,300 diagnoses in 2020, representing 20 per cent of all new cancer cases in men.² Approximately 34 per cent of men are diagnosed with mCRPC annually, and despite currently approved therapies, 16 per cent die each year.¹¹ 

About Lynparza (olaparib)
Lynparza was the first oral (PARP) inhibitor approved in Canada. Lynparza exploits tumour DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2, to selectively kill cancer cells.^9c Lynparza is the only PARP inhibitor currently approved in multiple tumour types in Canada including breast, ovarian, pancreatic and prostate cancers. In 2019, it was the first PARP inhibitor approved as a first-line maintenance therapy treatment in BRCA-mutated advanced ovarian cancer.

Lynparza is being jointly developed and commercialised by AstraZeneca and Merck, as part of a global strategic oncology collaboration.

About AstraZeneca 
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of primary and specialty care medicines that transform lives. Our primary focus is on three important areas of healthcare: Cardiovascular and Metabolic disease; Oncology; and Respiratory, Inflammation and Autoimmunity. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, we employ more than 675 employees across the country and our headquarters are located in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

About Merck  
For over a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships.

Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer's disease and infectious diseases including HIV and Ebola.

Based in Kirkland, Québec, Merck employs approximately 765 people across Canada. Merck is one of the top R&D investors in Canada, with investments totaling $69 million in 2018 and more than $1 billion since 2000. For more information about our operations in Canada, visit www.merck.ca and connect with us on YouTube and Twitter @MerckCanada. 

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA 
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

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References 

¹ De Bono et al. "Olaparib for Metastatic Castration-Resistant Prostate Cancer." New England Journal of Medicine. (2020); vol. 382:2091-2102. doi: 10.1056/NEJMoa1911440

² ESMO. (2019). Olaparib Outperforms Enzalutamide or Abiraterone Acetate in Men with mCRPC and HRR Alterations. Available at:

www.esmo.org/Oncology-News/Olaparib-Outperforms-Enzalutamide-or-Abiraterone-Acetate-in-Men-with-mCRPC-and-HRR-Alterations Accessed November 2020. 

³ Canadian Cancer Society. Prostate cancer statistics. Available at: https://www.cancer.ca/en/cancer-information/cancertype/prostate/statistics/?region=on Accessed August 2020.

⁴ Markowski. (2018). Germline genetic testing in prostate cancer – further enrichment in variant histologies? Oncoscience, p.62-64.

⁵ Castro, Elena et al. "Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 31,14 (2013): 1748-57. doi:10.1200/JCO.2012.43.1882

⁶ Annala, Matti et al. "Treatment Outcomes and Tumor Loss of Heterozygosity in Germline DNA Repair-deficient Prostate Cancer." European urology vol. 72,1 (2017): 34-42. doi:10.1016/j.eururo.2017.02.023

⁷ Annala, Matti et al. "Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer." Cancer discovery vol. 8,4 (2018): 444-457. doi:10.1158/2159-8290.CD-17-0937 

⁸ Albala. (2017). Imaging and treatment recommendations in patients with castrate-resistant prostate cancer. Rev Urol. 19(3), pp.200-202

⁹ Canadian Cancer Society. Survival statistics for prostate cancer. Available at: https://www.cancer.ca/en/cancer-information/cancertype/prostate/prognosis-and-survival/survival-statistics/?region=on. Accessed August 2020.

¹⁰ AstraZeneca Canada Inc., Lynparza® (olaparib) tablets. Product Monograph. October 2020. 

¹¹ De Bono et al. "Olaparib for Metastatic Castration-Resistant Prostate Cancer" [supplemental appendix]. New England Journal of Medicine. (2020); vol. 382:2091-2102. Available at: https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf. Accessed November 2020.

¹² Geynisman DM, Plimack ER, Zibelman M. Second-generation Androgen Receptor-targeted Therapies in Nonmetastatic Castration-resistant Prostate Cancer: Effective Early Intervention or Intervening Too Early? Eur Urol. 2016 Dec;70(6):971-973. doi: 10.1016/j.eururo.2016.05.026. Epub 2016 May 26. PMID: 27238654. 

SOURCE AstraZeneca Canada Inc.

AstraZeneca Corporate Communications, [email protected]; Hibaq Ali, Weber Shandwick Canada, [email protected]

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