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LYNPARZA® (olaparib) Approved by FDA for Treatment of HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer That Has Progressed Following Prior Treatment with Enzalutamide or Abiraterone

LYNPARZA® (olaparib) Approved by FDA for Treatment of HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer That Has Progressed Following Prior Treatment with Enzalutamide or Abiraterone

AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved LYNPARZA for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Patients will be selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

The approval was based on positive results from Phase 3 PROfound trial and published in The New England Journal of Medicine on April 28, 2020.

Prostate cancer is the second-most common cancer in men, and despite an increase in the number of available therapies for men with mCRPC, five-year survival remains low. HRR gene mutations occur in approximately 20-30% of patients with mCRPC.

Dr. Maha Hussain, one of the principal investigators of the PROfound trial and deputy director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said, “Prostate cancer has lagged behind other solid tumors in the era of precision medicine. I am thrilled by the approval of LYNPARZA, which now brings a molecularly targeted treatment for this patient population in the U.S. The PROfound trial was an international effort and I want to thank the patients, their families, the investigators and their teams involved in making it possible.”

Results from the PROfound trial showed LYNPARZA reduced the risk of disease progression or death by 66% (HR 0.34 [95% CI, 0.25-0.47], p<0.0001) and improved radiographic progression-free survival (rPFS) to a median of 7.4 months vs. 3.6 months with enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations, the primary endpoint and a subpopulation of HRR gene mutations. Results also showed LYNPARZA reduced the risk of radiographic disease progression or death by 51% (HR 0.49 [95% CI, 0.38-0.63], p<0.0001) and improved rPFS to a median of 5.8 months vs. 3.5 months with enzalutamide or abiraterone in the overall trial population of men with HRR gene-mutated mCRPC, a key secondary endpoint.

Additional results announced in April 2020 showed a statistically significant improvement in the key secondary endpoint of overall survival (OS) with LYNPARZA vs. enzalutamide or abiraterone in men with mCRPC and BRCA1/2 or ATM gene mutations. Results showed LYNPARZA reduced the risk of death by 31% (HR 0.69 [95% CI, 0.50-0.97], p=0.0175) and improved OS to a median of 19.1 months vs. 14.7 months for those treated with enzalutamide or abiraterone.

Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. 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.

Dave Fredrickson, executive vice president, head of the oncology business unit, AstraZeneca, said, “Today marks the first approval for LYNPARZA in prostate cancer. In the PROfound trial, LYNPARZA more than doubled the median radiographic progression-free survival and is the only PARP inhibitor to improve overall survival versus enzalutamide or abiraterone for men with BRCA or ATM mutations. These results further establish that genomic testing for HRR mutations should be considered a critical step for the diagnosis and determination of treatment options for men with advanced prostate cancer.”

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, “LYNPARZA is the only PARP inhibitor approved with Phase 3 data for men with HRR gene-mutated metastatic castration-resistant prostate cancer. This approval highlights the importance of genomic testing to identify treatment options for men in this patient population. We are proud to work in collaboration with AstraZeneca toward our overall goal of improving outcomes for patients.”

The most common adverse reactions (ARs) in the PROfound trial ≥10% for LYNPARZA compared to enzalutamide or abiraterone were anemia (46% vs. 15%), nausea (41% vs. 19%), fatigue (including asthenia) (41% vs. 32%), decreased appetite (30% vs. 18%), diarrhea (21% vs. 7%), vomiting (18% vs. 12%), thrombocytopenia (12% vs. 3%), cough (11% vs. 2%), and dyspnea (10% vs. 3%). Dose interruptions due to an AR occurred in 45% of patients receiving LYNPARZA and dose reductions due to an AR occurred in 22% of LYNPARZA patients. Discontinuation due to ARs occurred in 18% of LYNPARZA patients.

Fatal ARs occurred in 4% of patients treated with LYNPARZA. These included pneumonia (1.2%), cardiopulmonary failure (0.4%), aspiration pneumonia (0.4%), intestinal diverticulum (0.4%), septic shock (0.4%), Budd-Chiari Syndrome (0.4%), sudden death (0.4%), and acute cardiac failure (0.4%). Serious ARs occurred in 36% of patients receiving LYNPARZA. The most frequent serious ARs (≥2%) were anemia (9%), pneumonia (4%), pulmonary embolism (2%), fatigue/asthenia (2%) and urinary tract infection (2%).

LYNPARZA is currently under regulatory review in the European Union and other jurisdictions as a treatment for men with HRR gene-mutated mCRPC.

AstraZeneca and Merck are exploring additional trials in metastatic prostate cancer, including the ongoing Phase 3 PROpel trial evaluating LYNPARZA as a first-line therapy in combination with abiraterone acetate for patients with mCRPC vs. abiraterone acetate alone.