CLINICAL TRIALS PROFILE FOR OLAPARIB

505(b)(2) Clinical Trials for Olaparib

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT04538378 ↗	Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors	Recruiting	National Cancer Institute (NCI)	Phase 2	2021-07-07	Background: Lung cancers with EGFR mutations may develop resistance to therapies targeting this protein by evolving/being transformed into small cell or neuroendocrine cancers. There are no standard treatments for it. Researchers want to see if a new combination of drugs can help. Objective: To see if the combination of durvalumab and olaparib will cause tumors to shrink. Eligibility: Adults age 18 and older who had EGFR-mutated non-small-cell lung carcinoma (NSCLC) that was treated and now transformed to SCLC or another neuroendocrine tumor. Design: Participants will be screened under a separate protocol. They may have a tumor biopsy. Participants will have a physical exam. They will have a review of their symptoms, their medicines, and their ability to do their normal activities. They will have blood tests. They will have an electrocardiogram to evaluate their heart. Participants will have a computed tomography (CT) scan, a series of x-rays taken of parts of the body. Participants will get durvalumab on Day 1 of each 28-day cycle. It is given through a small plastic tube that is put in an arm vein. They will take olaparib by mouth twice every day. They will keep a medicine diary. Participants will take the study drugs until their disease gets worse or they have unacceptable side effects. About 30 days after they stop taking the study drugs, participants will have a follow-up visit. Then they will be contacted every 6 months for the rest of their life....

All Clinical Trials for Olaparib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00494234 ↗	Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Breast Cancer	Active, not recruiting	KuDOS Pharmaceuticals Limited	Phase 2	2007-06-15	The purpose of the study is to see if the drug KU 0059436 (olaparib) is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists
NCT00494234 ↗	Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Breast Cancer	Active, not recruiting	AstraZeneca	Phase 2	2007-06-15	The purpose of the study is to see if the drug KU 0059436 (olaparib) is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists
NCT00494442 ↗	Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer	Completed	KuDOS Pharmaceuticals Limited	Phase 2	2007-06-11	The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.
NCT00494442 ↗	Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer	Completed	AstraZeneca	Phase 2	2007-06-11	The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.
NCT00515866 ↗	Study to Assess the Safety & Tolerability of a PARP Inhibitor in Combination With Gemcitabine in Pancreatic Cancer	Completed	AstraZeneca	Phase 1	2007-08-01	The purpose of this study is to identify a safe and tolerable dose of the drug KU-0059436 that can be given in combination with gemcitabine chemotherapy for the treatment of pancreatic cancer.
NCT00516373 ↗	A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)	Active, not recruiting	AstraZeneca	Phase 1	2005-07-04	To determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetic-pharmacodynamic profile, and maximum tolerated dose (MTD) of KU-0059436 when administered orally to patients with advanced solid tumours. To further evaluate the safety and efficacy of KU-0059436 in an expanded cohort of BCRA-enriched population, primarily ovarian cancer patients
NCT00516438 ↗	Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan	Completed	KuDOS Pharmaceuticals Limited	Phase 1	2007-07-01	The purpose of this study is to identify a safe and tolerable dose of the drug KU-0059436 that can be given in combination with topotecan chemotherapy in patients with advanced solid tumours

Clinical Trial Conditions for Olaparib

Condition Name

Condition Name for Olaparib
Intervention	Trials
Ovarian Cancer	41
Breast Cancer	37
Prostate Cancer	18
Triple Negative Breast Cancer	12

Condition MeSH

Condition MeSH for Olaparib
Intervention	Trials
Ovarian Neoplasms	77
Breast Neoplasms	72
Carcinoma, Ovarian Epithelial	63
Neoplasms	58

Clinical Trial Locations for Olaparib

Trials by Country

Trials by Country for Olaparib
Location	Trials
Canada	166
France	139
Spain	116
United Kingdom	113
Japan	96

Trials by US State

Trials by US State for Olaparib
Location	Trials
New York	78
California	77
Texas	68
Florida	64
Pennsylvania	61

Clinical Trial Progress for Olaparib

Clinical Trial Phase

Clinical Trial Phase for Olaparib
Clinical Trial Phase	Trials
Phase 4	6
Phase 3	33
Phase 2/Phase 3	8

Clinical Trial Status

Clinical Trial Status for Olaparib
Clinical Trial Phase	Trials
Recruiting	151
Active, not recruiting	82
Not yet recruiting	68

Clinical Trial Sponsors for Olaparib

Sponsor Name

Sponsor Name for Olaparib
Sponsor	Trials
AstraZeneca	167
National Cancer Institute (NCI)	61
Merck Sharp & Dohme Corp.	38

Sponsor Type

Sponsor Type for Olaparib
Sponsor	Trials
Other	387
Industry	314
NIH	61

Olaparib: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction

Olaparib, marketed as Lynparza, is a groundbreaking poly (ADP-ribose) polymerase (PARP) inhibitor that has revolutionized the treatment of various cancers, particularly those associated with BRCA mutations. Here, we delve into the latest clinical trial updates, market analysis, and future projections for this pivotal drug.

Mechanism of Action

Olaparib acts by inhibiting PARP enzymes, including PARP1, PARP2, and PARP3, which are crucial for the repair of single-strand DNA breaks. By inhibiting these enzymes, olaparib enhances the cytotoxicity of DNA-damaging agents and reverses tumor cell chemoresistance and radioresistance, leading to cell death[2].

Clinical Trials Update

OlympiA Trial

One of the most significant clinical trials for olaparib is the OlympiA trial, which investigated the use of olaparib as an adjuvant treatment for patients with high-risk, BRCA-positive, HER2-negative breast cancer. The trial demonstrated that patients who received olaparib after standard treatment had better survival outcomes compared to those who received a placebo. After a median follow-up of 6.1 years, olaparib reduced the risk of invasive disease-free survival and distant disease-free survival by 35%. Additionally, there was a 28% reduction in the risk of death, with no increase in the risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)[1].

PROpel Trial

In the context of metastatic castration-resistant prostate cancer (mCRPC), the PROpel trial evaluated the combination of olaparib with abiraterone and prednisone. This combination showed a clinically significant increase in overall survival (OS) and radiological progression-free survival (rPFS) compared to abiraterone alone. However, the evidence is still at a low level of certainty, and longer follow-up is needed to confirm long-term benefits and risks[3].

Osteosarcoma Trial

A phase 2 clinical trial is currently underway to evaluate the effectiveness of combining olaparib with ceralasertib in patients with recurrent osteosarcoma. This study involves two cohorts: one with unresectable osteosarcoma and another with lung-only resectable osteosarcoma. Participants will receive treatment for up to 24 cycles (2 years), and the study aims to enroll approximately 63 patients[4].

Market Analysis

Current Market Performance

Olaparib has been a market leader in the PARP inhibitor space since its first approval in 2014 for BRCA-mutated metastatic ovarian cancer. As of 2023, global sales of Lynparza stood at $2.811 billion, with a historical growth rate (CAGR) of 17% between 2020 and 2023[2].

Market Projections

GlobalData predicts that Lynparza will continue to dominate the PARP market, with projected global sales reaching $4 billion by 2027. This growth is driven by new licenses and expanded indications in various cancers, including breast, prostate, pancreatic, and ovarian tumors. Lynparza is expected to capture over 68% of the global PARP inhibitors market by 2027[5].

Competitive Landscape

While Lynparza leads the market, other PARP inhibitors like GSK's Zejula (niraparib) and Clovis Oncology's Rubraca (rucaparib) also play significant roles. However, the market impact of these competitors has been limited, especially after the withdrawal of these drugs from heavily pretreated ovarian cancer patients due to potential detrimental effects on patient survival[5].

Future Outlook

Ongoing Clinical Trials

Lynparza is currently involved in 123 ongoing phase clinical trials across multiple cancer types and combinations, highlighting its pivotal role in oncology. These trials are expected to further expand its indications and solidify its position in the market[5].

Patent Expiry and Generic Erosion

The patent protection for Lynparza in the U.S. is set to expire in 2028, which is anticipated to lead to a downshift in sales due to generic erosion. However, AstraZeneca is working on an experimental selective PARP1 inhibitor, saruparib, which has shown early promise in phase 1/2 trials for homologous recombination repair (HRR)-deficient advanced breast cancers. If approved, saruparib could further strengthen AstraZeneca's lead in the PARP inhibitor market[5].

Cost-Effectiveness and Economic Impact

The combination of olaparib with abiraterone in mCRPC has been associated with a significant survival benefit but at a high cost. The incremental cost-effectiveness ratio (ICER) for this combination was estimated at $160,535 per quality-adjusted life year (QALY) gained, indicating a substantial economic burden. However, the clinical benefits and the potential for long-term survival gains make it a valuable treatment option despite the costs[3].

Key Takeaways

• Clinical Efficacy: Olaparib has demonstrated significant long-term survival benefits in high-risk, BRCA-positive breast cancer and other cancer types.
• Market Dominance: Lynparza is projected to continue leading the PARP inhibitor market with expected global sales of $4 billion by 2027.
• Ongoing Research: Over 120 clinical trials are ongoing, exploring new indications and combinations.
• Economic Considerations: While costly, the combination therapies involving olaparib offer substantial clinical benefits.
• Future Challenges: Patent expiry in 2028 may lead to generic competition, but new drugs like saruparib could maintain AstraZeneca's market lead.

FAQs

Q: What is the mechanism of action of olaparib?

A: Olaparib acts by inhibiting PARP enzymes, which are crucial for the repair of single-strand DNA breaks, thereby enhancing the cytotoxicity of DNA-damaging agents and reversing tumor cell chemoresistance and radioresistance[2].

Q: What are the key findings of the OlympiA trial?

A: The OlympiA trial showed that olaparib significantly improved survival outcomes for patients with high-risk, BRCA-positive, HER2-negative breast cancer, reducing the risk of invasive disease-free survival and distant disease-free survival by 35% and the risk of death by 28%[1].

Q: How does olaparib perform in the market compared to other PARP inhibitors?

A: Lynparza is expected to capture over 68% of the global PARP inhibitors market by 2027, significantly outperforming other PARP inhibitors like Zejula and Rubraca[5].

Q: What are the economic implications of using olaparib in combination therapies?

A: The combination of olaparib with abiraterone in mCRPC is associated with a high ICER of $160,535 per QALY gained, indicating a substantial economic burden despite significant clinical benefits[3].

Q: What are the future prospects for olaparib after patent expiry?

A: While patent expiry in 2028 may lead to generic competition, AstraZeneca's development of new drugs like saruparib could help maintain their market lead in the PARP inhibitor space[5].

Sources

1. PARP Inhibition Shows Long-term Survival Benefits for Patients With High-risk, BRCA-positive Breast Cancer in OlympiA Trial - American Association for Cancer Research.
2. The Global Drug sales of Lynparza - GlobalData.
3. Pharmacoeconomic Review - Olaparib (Lynparza) - NCBI Bookshelf.
4. Olaparib With Ceralasertib in Recurrent Osteosarcoma - ClinicalTrials.gov.
5. AstraZeneca and Merck's Lynparza set to 'dominate' PARP market - FiercePharma.