LYNPARZA (OLAPARIB) APPROVED IN THE UK AS COMBINATION THERAPY FOR TREATMENT OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHEN CHEMOTHERAPY IS NOT CLINICALLY INDICATED

LYNPARZA (OLAPARIB) APPROVED IN THE UK AS COMBINATION THERAPY FOR TREATMENT OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHEN chemotherapy is not clinically indicated

 

• Approval from the MHRA is based on positive data from the PROpel Phase III trial and olaparib is the first PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal agent in first-line metastatic castration-resistant prostate cancer (mCRPC).^[1]
• Combination therapy of olaparib with abiraterone and prednisone or prednisolone showed a 34% reduction in risk of disease progression or death versus abiraterone and prednisone or prednisolone in patients with mCRPC with or without homologous recombination repair (HRR) gene mutations.^[1]
• Approximately 140 men are diagnosed with prostate cancer each day in the UK, and around 10-20% of patients with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these patients will have metastases at the time of CRPC diagnosis.^[2],[3]

 

London, UK, Monday 20 March 2023 – AstraZeneca and MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA [NYSE: MRK]) today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for olaparib in the United Kingdom for use as combination therapy with abiraterone and prednisone or prednisolone, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated.^[4]

 

Prostate cancer is a major cause of disease and mortality among men and the fifth most common cause of cancer death globally.^[5] In the UK, more than 52,000 men are diagnosed with prostate cancer every year, accounting for more than 140 cases per day.² Around 10-20% of patients with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years which occurs when prostate cancer evolves to resist standard treatment with androgen deprivation therapy (ADT).³ Most CRPCs are metastatic (mCRPC), meaning the cancer has spread to a site distant from the prostate.^[6]

 

Professor Noel Clarke, Professor of Urological Oncology at The Christie, and Salford Royal Hospitals, said: “This approval by the MHRA is an important next step for healthcare professionals and their patients in the UK with this specific type of prostate cancer. These data from the PROpel Phase III trial underline the therapeutic potential of new first-line treatment options for patients with metastatic castration-resistant prostate cancer, especially given that many have a much-shortened life-span when their disease becomes castrate resistant.”

 

The decision from the MHRA was based on results from the PROpel Phase III trial which showed that AstraZeneca and MSD’s olaparib in combination with abiraterone significantly improved radiographic progression-free survival (rPFS) versus abiraterone alone as a first-line treatment for patients with mCRPC regardless of their biomarker status.¹

 

Results also show that combination therapy reduced the risk of disease progression or death by 34% versus abiraterone alone (median PFS 24.8 months vs 16.6 months; based on a hazard ratio [HR] of 0.66; 95% confidence interval [CI] 0.54-0.81; p<0.0001).¹ At the time of data cut off, analysis of overall survival (OS) was at 40% maturity, the trial will continue to assess OS as a key secondary endpoint.^[7]

 

Ed Piper, Medical and Scientific Affairs Director, AstraZeneca UK, said: “We are delighted that olaparib has been authorised by the MHRA today, opening a new chapter in prostate cancer treatment. This additional therapy option supports our overall ambition to reduce the national burden of prostate cancer and we are continuing to work with NICE and NHS England to secure access as quickly as possible for patients. Medical advances like these offer hope of further progressing the UK as a leader in life science.”

 

David Long, Head of Oncology at MSD UK, said: “Prostate cancer is the most common cancer in men in the UK and advanced prostate cancer is associated with a significant mortality rate. This approval from the MHRA marks important progress in advancing a new treatment option to address the significant unmet need of patients with metastatic castration-resistant prostate cancer.”

 

Results from additional unpowered exploratory efficacy endpoints are consistent with the treatment benefit of olaparib and abiraterone compared to monotherapy with abiraterone alone in the overall trial population, including objective response rate (ORR) (odds ratio, 1.60; 95% CI,1.02-2.53), time to first subsequent therapy (TFST) (HR, 0.74; 95% CI, 0.61-0.90), second progression-free survival (PFS2) (HR, 0.69; 95% CI, 0.51-0.94), as well as prostate-specific antigen levels and circulating-tumour-cell counts.¹

 

Olaparib has been associated with adverse reactions generally of mild or moderate severity (CTCAE grade 1 or 2) and generally not requiring treatment discontinuation.⁴

 

The most frequently observed adverse reactions across clinical trials in patients receiving Lynparza monotherapy (≥ 10%) were nausea, fatigue/asthenia, anaemia, vomiting, diarrhoea, decreased appetite, headache, neutropenia, dysgeusia, cough, leukopenia, dizziness, dyspnoea and dyspepsia.⁴ The Grade ≥ 3 adverse reactions occurring in > 2% of patients were anaemia (15%), neutropenia (5%), fatigue/asthenia (4%), leukopenia (3%) and thrombocytopenia (2%).⁴

 

– ENDS –

CONTACTS

UK Media Enquiries

Emma White, AstraZeneca: 07385 516437 / emma.white1@astrazeneca.com

Jack Faulkner, Edelman: 07813 407324 / jack.faulkner@edelman.com 

 

NOTES TO EDITORS

 

About Lynparza

Olaparib is a potent inhibitor of human poly (ADP-ribose) polymerase (PARP) enzymes that is targeted to block DNA repair in cancer cells harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2.⁴ Inhibition of PARP proteins with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks (DSBs) and cancer cell death.⁴

 

Lynparza (olaparib) is indicated in the United Kingdom for the treatment of prostate cancer as:

• combination therapy with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.⁴
• monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.⁴

 

For more information about olaparib, a summary of product characteristics (SmPC) can be found here: https://www.medicines.org.uk/emc/product/9204/smpc#gref.

 

About PROpel

PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of Lynparza versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the first line setting.^[8]

 

Men in both treatment groups will also receive either prednisone or prednisolone twice daily.⁸ The primary endpoint is radiographic progression-free survival (rPFS) and secondary endpoints include overall survival (OS), time to disease progression or death (PFS2), and time to first subsequent therapy (TFST).⁸

 

Over 700 patients globally were randomised in PROpel in a 1:1 ratio to treatment with either olaparib and abiraterone or placebo and abiraterone.⁸

 

Patients receive oral treatment with olaparib 300 mg twice daily + abiraterone 1000 mg once daily or placebo twice daily + abiraterone 1000 mg once daily.⁸ Patients in both treatment groups also receive either prednisone 5 mg twice daily or prednisolone 5 mg twice daily.⁸

For more information about the trial please visit ClinicalTrials.gov.

 

About Metastatic castration-resistant prostate cancer

Metastatic prostate cancer is associated with a significant mortality rate.^[9] Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.^[10]

 

In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.³ Approximately 10-20% of patients with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these patients will have metastases at the time of CRPC diagnosis.³

 

Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.^[11] Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent (NHA) treatment, once patients failed first line therapy, the treatment effect of second line anti-cancer therapy appears to diminish significantly hence there is high unmet medical need in this population.^{3,[12],[13],[14]}

 

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.

 

With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. AstraZeneca is based in six different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,600 employees work in research and development, manufacturing, supply, sales and marketing. We supply around 35 different medicines to the NHS.

 

For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK.

 

About MSD

At MSD, known as Merck & Co., Inc., Rahway, NJ, USA in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd-uk.com and connect with us @MSDintheUK on Twitter, LinkedIn, Instagram, YouTube and Facebook.   

 

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbour 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. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialise, 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 the global outbreak of novel coronavirus disease (COVID-19); 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.

 

The company undertakes no obligation to publicly update any forward-looking statement, whether because of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2021 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

 

References

 

 

 

[1] Clarke NW, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence 2022;1(9).

[2] About Prostate Cancer. Prostate Cancer UK. Available at: https://prostatecanceruk.org/prostate-information/about-prostate-cancer. Last accessed: March 2023.

[3] Kirby M, et al. Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice. 2021;65(11):1180-1192.

[4] Electronic Medicines Compendium (EMC). Lynparza 100 mg film-coated tablets – Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/9204/smpc#gref. Last accessed: March 2023.

[5] Pernar CH et al. The Epidemiology of Prostate Cancer. Cold Spring Harb Perspect Med 2018; 8(12).

[6] Advanced Prostate Cancer. Urology Care Foundation. Available at: https://www.urologyhealth.org/urology-a-z/a_/advanced-prostate-cancer. Last accessed: March 2023

[7] Saad F, et al. Biomarker analysis and updated results from the Phase III PROpel trial of abiraterone (abi) and olaparib (ola) vs abi and placebo (pbo) as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Poster 13570. Presented at the 2022 ESMO Virtual Plenary Session, 16–18 March 2022.

[8] ClinicalTrials.gov. Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer. Available at: https://clinicaltrials.gov/ct2/show/NCT03732820. Last accessed: March 2023.

[9] Chowdhury S, et al. Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer: the prostate cancer registry. Target Oncol. 2020;15(3):301-15.

[10] Cancer.Net. Treatment of metastatic castration-resistant prostate cancer. Available at: www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer. Last accessed: March 2023.

[11] George D, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clinical Genitourinary Cancer. 2020 Aug;18(4):284-294.

[12] UroToday. What is Changing in Advanced Prostate Cancer? Available at: https://www.urotoday.com/journal/everyday-urology-oncology-insights/articles/122176-what-is-changing-in-advanced-prostate-cancer.html. Last accessed: March 2023.

[13] Liu J, et al. Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database. Scientific Report. 2020;10(4240):2020.

[14] UroToday. Beyond First-line Treatment of Metastatic Castrate-resistant Prostate Cancer. Available at: https://www.urotoday.com/library-resources/mcrpc-treatment/114592-beyond-first-line-treatment-of-metastatic-castrate-resistant-prostate-cancer.html. Last accessed: March 2023.