Conclusion: Lynparza shows significant clinical benefit in its newest indication, second-line HRR-mutated metastatic castration-resistant prostate cancer. Even when competing against generically priced Zytiga, Lynparza’s efficacy advantages support its current price.
On April 24th, Lynparza (olaparib, AstraZeneca/Merck) announced positive data in second-line homologous recombination repair gene mutated (HRRm) metastatic castration-resistant prostate cancer (mCRPC). Assuming approval, this is the PARP inhibitor’s sixth indication, joining BRCA-mutated pancreatic, ovarian, and breast cancer.
An FDA approval is expected to follow the data published from the PROfound study, a prospective, multicenter, randomized, open-label, Phase III trial testing Lynparza versus enzalutamide or abiraterone in HRRm patients. The trial was broken out into two cohorts, BRCA- and ATM- mutated patients, and other HRR mutations. Lynparza showed significant clinical efficacy over the control arm in both groups, more than doubling progression-free survival (7.8 vs. 3.6 months in HRRm writ-large). These improvements come to a high-need population—patients with HRR-mutated prostate cancer are on average younger and have more aggressive disease than non-mutated patients.
The waterfall chart below illustrates how Lynparza compares to Zytiga/Xtandi across the different domains of unmet need in HRRm writ-large. Looking at the chart, it’s clear that Lynparza’s efficacy and reduction of mortality offset its higher cost; in the HRRm population the overall improvement as measured by our Clinical Innovation score of 9.1% suggests a well differentiated agent (at the high end of our medium range). In BRCA/ATM mutated patients, Lynparza performs even better, with an overall improvement of 16.6%, which qualifies as high Clinical Innovation.
We can plot Lynparza’s clinical benefit over Zytiga/Xtandi against its increase in price. Doing so, we see that in both HRRm writ-large (top) and BRCA/ATM mutated (bottom) mCRPC Lynparza falls neatly into the “cloud,” a set of exemplars that have achieved good market access. This is good news for AstraZeneca and Merck— with generic Zytiga now widely available, Lynparza needed to show significant benefit to battle a drug with generic pricing, and it does just that.
Given Lynparza’s significant reduction in overall unmet need in second-line HRRm mCRPC, we expect it to be approved and adopted quickly.
