Summary Basis of Decision for Lynparza

Review decision

The Summary Basis of Decision explains why the product was approved for sale in Canada. The document includes regulatory, safety, effectiveness and quality (in terms of chemistry and manufacturing) considerations.

Product type:

Drug

Contact: Bureau of Metabolism, Oncology, and Reproductive Sciences

Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for Lynparza is located below.

Recent Activity for Lynparza

SBDs written for eligible drugs approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive. PAATs will be updated regularly with post-authorization activity throughout the product's life cycle.

Post-Authorization Activity Table (PAAT) for Lynparza

Updated: 2024-01-03

The following table describes post-authorization activity for Lynparza, a product which contains the medicinal ingredient olaparib. For more information on the type of information found in PAATs, please refer to the Frequently Asked Questions: Summary Basis of Decision (SBD) Project: Phase II and to the List of abbreviations found in Post-Authorization Activity Tables (PAATs).

For additional information about the drug submission process, refer to the Guidance Document: The Management of Drug Submissions and Applications.

Drug Identification Number (DIN):

DIN 02454408 – 50 mg olaparib, capsule, oral administration
DIN 02475200 – 100 mg olaparib, tablet, oral administration
DIN 02475219 – 150 mg olaparib, tablet, oral administration

Post-Authorization Activity Table (PAAT)

Activity/Submission Type, Control Number	Date Submitted	Decision and Date	Summary of Activities
SNDS-C # 271885	2023-01-30	Issued NOC 2023-12-13	Submission filed as a Level I – Supplement in response to commitments made as per the provisions of the NOC issued under the Guidance Document: Notice of Compliance with Conditions (NOC/c) for the use of Lynparza (olaparib) tablets as adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (BRCAm), human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. The submission provided the updated efficacy analysis of the pivotal OlympiA study and fulfilled the conditions listed in the Letter of Undertaking dated 2022-07-14 (SNDS # 259417). The data were reviewed and considered acceptable. As a result of the submission, the conditions were removed from the NOC that had been issued 2022-07-27.
SNDS-C # 270095	2022-11-25	Issued NOC 2023-10-24	Submission filed as a Level I – Supplement in response to commitments made as per the provisions of the NOC issued under the Guidance Document: Notice of Compliance with Conditions (NOC/c) for the use of Lynparza (olaparib) tablets in the treatment of patients with BRCA wild-type ovarian cancer (SNDS #205344). The submission provided results from the confirmatory trial (OPINION) outlined in the Letter of Undertaking dated 2018-04-26. The data were reviewed and considered acceptable. As a result of the submission, the conditions were removed from the NOC that had been issued 2018-05-04.
PBRER-C # 272675	2023-02-22	Filed 2023-07-20	Submission filed in response to commitments made as per the provisions of the Guidance Document: Notice of Compliance with Conditions (NOC/c). PBRER-C for the period 2021-12-16 to 2022-12-15. The information was reviewed and found acceptable.
PBRER-C # 259765	2022-02-23	Filed 2023-07-20	Submission filed in response to commitments made as per the provisions of the Guidance Document: Notice of Compliance with Conditions (NOC/c). PBRER-C for the period 2020-12-16 to 2021-12-15. The information was reviewed and found acceptable.
SNDS # 265427	2022-06-22	Issued NOC under NOC/c Guidance 2023-07-11	Submission filed as a Level I – Supplement for a new indication. The indication authorized was: Lynparza in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious germline and/or somatic BRCA-mutated metastatic castration resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated. BRCA mutation must be confirmed before Lynparza treatment is initiated. The submission was reviewed and considered acceptable, and an NOC was issued under the Guidance Document: Notice of Compliance with Conditions (NOC/c). A Regulatory Decision Summary was published.
SNDS # 263013	2022-03-31	Issued NOC 2022-08-05	Submission filed as a Level II – Supplement (Safety) to update the PM with new safety information. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Warnings and Precautions, and Adverse Reactions sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 259417	2021-12-09	Issued NOC under NOC/c Guidance 2022-07-27	Submission filed as a Level I – Supplement for a new indication. The submission was reviewed under the Priority Review of Drug Submissions Policy. The indication authorized was: the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. The submission was reviewed and considered acceptable, and an NOC was issued under the NOC/c Guidance. A Regulatory Decision Summary was published.
SNDS # 252153	2021-04-27	Issued NOC 2022-02-21	Submission filed as a Level I – Supplement to update the PM with new safety information and final data from studies SOLO2, PROfound, and POLO. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Adverse Reactions and Clinical Trials sections of the PM. An NOC was issued.
PBRER-C # 250140	2021-03-03	Filed 2021-12-17	Submission filed in response to commitments made as per the provisions of the NOC/c Guidance. PBRER-C for the period 2019-12-16 to 2020-12-15. The information was reviewed and found acceptable.
PBRER-C # 237101	2020-03-12	Filed 2021-12-17	Submission filed in response to commitments made as per the provisions of the NOC/c Guidance. PBRER-C for the period 2018-12-16 to 2019-12-15. The information was reviewed and found acceptable.
SNDS # 253448	2021-06-04	Issued NOC 2021-09-28	Submission filed as a Level I – Supplement to update the bottle labels. The submission was reviewed and considered acceptable, and an NOC was issued.
SNDS # 249369	2021-02-09	Issued NOC 2021-06-04	Submission filed as a Level II – Supplement (Safety) to update the PM with new safety information. As a result of the SNDS, modifications were made to the Adverse Reactions section of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 246316	2020-11-17	Issued NOC 2021-03-25	Submission filed as a Level II – Supplement (Safety) to update the PM with new safety information. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Warnings and Precautions, and Adverse Reactions sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 245879	2020-10-30	Cancellation Letter Received 2021-02-12	Submission filed as a Level II – Supplement (Safety) to update the PM for Lynparza capsules with new safety information. The sponsor cancelled the submission before Health Canada completed the review, because the DIN for Lynparza capsules had been cancelled.
DIN 02454408 cancelled (post market)	Not applicable	Discontinuation date: 2021-01-11	The manufacturer notified Health Canada that sale of the drug has been discontinued post market. Health Canada cancelled the DIN(s) pursuant to section C.01.014.6(1)(a) of the Food and Drug Regulations.
SNDS # 235698	2020-01-31	Issued NOC 2020-08-21	Submission filed as a Level I – Supplement for a new indication for Lynparza tablets. The submission was reviewed under the Priority Review of Drug Submissions Policy. The indication authorized was: the treatment of adult patients with deleterious or suspected deleterious germline and/or somatic BRCA- or ATM-mutated metastatic castration-resistant prostate cancer who have progressed following prior treatment with a new hormonal agent. The submission was reviewed and considered acceptable, and an NOC was issued.
SNDS # 229268	2019-06-28	Issued NOC 2020-06-03	Submission filed as a Level I – Supplement to expand the use of Lynparza capsules to include patients with moderate hepatic impairment and to update the PM with new safety and efficacy information. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Warnings and Precautions, Drug Interactions, and Dosage and Administration sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 229261	2019-06-28	Issued NOC 2020-05-20	Submission filed as a Level I – Supplement to expand the use of Lynparza tablets to include patients with moderate hepatic impairment and to update the PM with new safety and efficacy information. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Warnings and Precautions, Drug Interactions, and Dosage and Administration sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 230309	2019-08-01	Issued NOC 2020-02-14	Submission filed as a Level I – Supplement for a new indication for Lynparza tablets. The submission was reviewed under the Priority Review of Drug Submissions Policy. The indication authorized was: maintenance therapy of adult patients with deleterious or suspected deleterious germline BRCA-mutated metastatic adenocarcinoma of the pancreas whose disease has not progressed on a minimum of 16 weeks of first-line platinum-based chemotherapy. The submission was reviewed and considered acceptable, and an NOC was issued.
PBRER-C # 225233	2019-03-04	Filed 2019-07-12	Submission filed in response to commitments made as per the provisions of the NOC/c Guidance. PBRER-C for the period 2017-12-16 to 2018-12-15. The information was reviewed and found acceptable.
SNDS # 219799	2018-10-25	Issued NOC 2019-05-06	Submission filed as a Level I – Supplement for a new indication for Lynparza tablets. The submission was reviewed under the Priority Review of Drug Submissions Policy. The indication authorized was: maintenance therapy of adult patients with advanced BRCA-mutated high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to first-line platinum-based chemotherapy. The submission was reviewed and considered acceptable, and an NOC was issued.
PBRER-C # 214009	2018-02-27	Filed 2019-05-06	Submission filed in response to commitments made as per the provisions of the NOC/c Guidance. PBRER-C for the period 2016-12-15 to 2017-12-15. The information was reviewed and found acceptable.
NC # 224063	2019-01-25	Issued NOL 2019-03-26	Submission filed as a Level II (90 day) Notifiable Change to update the PM for Lynparza capsules with new safety information. As a result of the NC, modifications were made to the Warnings and Precautions, and Adverse Reactions sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. The submission was reviewed and considered acceptable, and an NOL was issued.
NC # 220476	2018-11-22	Issued NOL 2019-03-26	Submission filed as a Level II (90 day) Notifiable Change to update the PM for Lynparza tablets with new safety information. As a result of the NC, modifications were made to the Warnings and Precautions, and Adverse Reactions sections of the PM, and corresponding changes were made to Part III: Patient Medication Information. The submission was reviewed and considered acceptable, and an NOL was issued.
SNDS # 218057	2018-07-25	Issued NOC 2018-09-25	Submission filed as a Level I – Supplement to update the Lynparza 50 mg capsules packaging components with information regarding the change in product storage conditions. The information was reviewed and considered acceptable. An NOC was issued.
SNDS # 214397	2018-03-16	Issued NOC 2018-05-24	Submission filed as a Level I – Supplement to revise the outer carton and inner bottle labels for Lynparza capsules. The information was reviewed and considered acceptable. An NOC was issued.
Drug product (DINs 02475200, 02475219) market notification	Not applicable	Date of first sale: 2018-05-23	The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations.
SNDS # 210204	2017-10-13	Issued NOC 2018-05-08	Submission filed as a Level I – Supplement to obtain marketing authorization for Lynparza tablets (olaparib) as monotherapy for the treatment of adult patients with germline breast cancer susceptibility gene (BRCA)-mutated human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously been treated with chemotherapy. Regulatory Decision Summary published.
SNDS # 205344	2017-05-05	Issued NOC 2018-05-04 Issued NOC under NOC/c Guidance 2018-05-04	Submission filed as a Level I – Supplement to obtain market authorization for a new formulation of Lynparza (olaparib tablets) 100 mg and 150 mg for the proposed indication as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy. Efficacy and safety findings from the SOLO2 study support a positive benefit-risk profile for olaparib tablets in patients with BRCA mutated ovarian cancer. The sponsor provided promising evidence from Study 19 demonstrating superior benefit of olaparib capsules versus placebo in patients with BRCA wild-type ovarian cancer. The link between capsule and tablet is based on comparative bioavailability data showing that exposure to olaparib tablets 300 mg twice daily in ovarian cancer patients from the SOLO2 study was within the range observed in a similar patient population receiving olaparib capsules 400 mg twice daily. Confirmatory evidence of the benefit of olaparib tablets in patients with BRCA wild-type status will be derived from the final analysis of the Phase IIIb open-label single-arm study (OPINION) in patients with BRCA wild-type ovarian cancer receiving olaparib tablets. Overall, the benefit-risk profile of Lynparza tablets for use in the treatment of ovarian, fallopian tube cancer, or primary peritoneal cancer in both BRCA mutated and BRCA wild-type is considered favourable. Risk mitigation strategies have been agreed to in order to minimize medication confusion errors during dual market availability of Lynparza tablets and capsules. The submission was reviewed and considered acceptable. An NOC was issued for the use of Lynparza tablets in the treatment of ovarian and fallopian tube cancer in BRCA mutated patients. An NOC was issued under the Guidance Document: Notice of Compliance with Conditions (NOC/c) for the use of Lynparza tablets in the treatment of ovarian and fallopian tube cancer in BRCA wild-type patients. New DINs (02475200, 02475219) were issued for the new dosage form. A Regulatory Decision Summary was published.
SNDS-C # 205873	2017-05-24	Issued NOC 2018-05-02	Submission filed as a Level I – Supplement in response to commitments made as per the provisions of the NOC/c Guidance. The submission was filed to obtain an NOC for Lynparza (olaparib) capsules 50 mg by fulfilling the final confirmatory requirements outlined in the Letter of Undertaking dated March 31, 2016. Final data from pivotal Study 19 and supporting data from SOLO-2 provided confirmatory evidence of the benefit of Lynparza in patients with BRCA mutated ovarian, fallopian tube and primary peritoneal cancer. These data are considered to fulfill the requirements to convert from a conditional approval to full approval for olaparib capsules. Based on a positive benefit-risk profile for olaparib capsules for BRCA mutated ovarian, fallopian tube or primary peritoneal cancer patients, an NOC was recommended.
Drug Recall	Not applicable	Posted 2018-02-23	Drug Recall posted on the Healthy Canadians website for the healthcare professionals, general public, and hospitals.
NC # 211221	2017-11-17	Issued NOL 2018-02-20	Submission filed as a Level II (90 day) Notifiable Change (Risk Management Change) to update the PM with new safety information. As a result of the NC, modifications were made to the Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections of the PM, and corresponding changes were made to the PM Part III: Patient Medication Information. The submission was reviewed and considered acceptable, and an NOL was issued.
PBRER-C # 203386	2017-03-01	Filed 2018-01-10	Submission filed in response to commitments made as per the provisions of the NOC/c Guidance. PBRER-C for the period 2015-12-16 to 2016-12-15. The information was reviewed and found acceptable.
SNDS # 197364	2016-08-04	Issued NOC under NOC/c Guidance 2017-06-22	Submission filed as a Level I – Supplement to update the PM. As a result of the SNDS, modifications were made to the Warnings and Precautions, Drug Interactions, and Dosage and Administration sections of the PM, and corresponding changes were made to the PM Part III: Patient Medication Information. The benefit/risk profile for Lynparza remains positive when used for its approved indication. The submission was reviewed and considered acceptable, and an NOC was issued.
Drug product (DIN 02454408) market notification	Not applicable	Date of first sale: 2016/05/16	The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations.
NDS # 182823	2015/03/16	Issued NOC 2016/04/29	Notice of Compliance issued for New Drug Submission.

Summary Basis of Decision (SBD) for Lynparza

Date SBD issued: 2016-07-12

The following information relates to the New Drug Submission for Lynparza.

Olaparib, 50 mg, capsules, oral

Drug Identification Number (DIN):

02454408

AstraZeneca Canada Inc.

New Drug Submission Control Number: 182823

On April 29, 2016, Health Canada issued a Notice of Compliance under the Notice of Compliance with Conditions (NOC/c) Guidance to AstraZeneca Canada Inc. for the drug product, Lynparza. The product was authorized under the NOC/c Guidance on the basis of the promising nature of the clinical evidence, and the need for further follow-up to confirm the clinical benefit. Patients should be advised of the fact that the market authorization was issued with conditions.

The market authorization was based on quality (chemistry and manufacturing), non-clinical (pharmacology and toxicology), and clinical (pharmacology, safety, and efficacy) information submitted. Based on Health Canada's review, the benefit/risk profile of Lynparza is favourable as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

Platinum sensitivity is defined as disease progressing at least 6 months after completion of the penultimate platinum chemotherapy.

1 What was approved?

Lynparza, an antineoplastic agent, was authorized as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

Platinum sensitivity is defined as disease progressing at least 6 months after completion of the penultimate platinum chemotherapy.

There is limited clinical data in patients aged 65 or over.

The safety and efficacy of Lynparza in children and adolescents (<18 years of age) have not been established.

Lynparza is contraindicated for patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the capsule. Lynparza was approved for use under the conditions stated in the Lynparza Product Monograph taking into consideration the potential risks associated with the administration of this drug product.

Lynparza (50 mg olaparib) is presented as a capsule. In addition to the medicinal ingredient, olaparib, the capsule contains lauroyl macrogol-32 glycerides, hypromellose, titanium dioxide (E171), gellan gum (E418), potassium acetate, shellac, and iron oxide black (E172).

For more information, refer to the Clinical, Non-Clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.

Additional information may be found in the Lynparza Product Monograph, approved by Health Canada and available through the Drug Product Database.

2 Why was Lynparza approved?

Health Canada considers that the benefit/risk profile of Lynparza is favourable as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy. Platinum sensitivity is defined as disease progressing at least 6 months after completion of the penultimate platinum chemotherapy. Lynparza was authorized under the NOC/c Guidance on the basis of the promising nature of the clinical evidence, and the need for further follow-up to confirm the clinical benefit.

Ovarian cancer is the fifth leading cause of cancer mortality in Canadian women. It is a serious disease which is generally detected at an advanced stage, with 5-year relative survival rates of approximately 45% across all stages. The majority of cases of ovarian cancer are of epithelial origin. Fallopian tube cancer and primary peritoneal cancer are less common neoplasms but are managed in a similar manner to epithelial ovarian cancer. They have similar responses to anti-cancer treatment.

Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) are human genes that belong to a class known as tumor suppressors. In normal cells, BRCA1 and BRCA2 help ensure the stability of the cell's genetic material and prevent cancer formation. Germline and/or somatic BRCA 1/2 mutations occur in approximately 18% of all ovarian cancers and 23% of high-grade serous cancers. The number of patients with BRCA-mutated ovarian cancer is estimated at approximately 500 new cases annually in Canada. Treatment for patients with newly diagnosed, advanced ovarian cancer generally consists of surgery followed by platinum-based chemotherapy in combination with a taxane. There are currently no licensed treatments in Canada with proven efficacy that could be administered after a response to platinum-containing regimens. Patients are usually not offered anti-cancer therapy until subsequent disease progression.

The efficacy data supporting the maintenance indication for Lynparza was derived from one Phase II pivotal study (Study 19) and one supporting Phase II study (Study 41). In Study 19, 265 patients were randomized to receive treatment (136 in the Lynparza group and 129 in the placebo group). The BRCA-mutated subgroup in Study 19 contained 136 patients (74 patients received Lynparza and 62 patients received placebo). In Study 41, 162 patients were randomized, but only 25% of the study population had a known BRCA mutation. The pivotal study was well-designed and well-conducted.

Subgroup analyses demonstrated that ovarian cancer patients with a BRCA mutation received the greatest progression-free survival (PFS) benefit from treatment with Lynparza maintenance therapy with a statistically significant and clinically meaningful improvement in median PFS of 6.9 months over placebo. The median PFS was 11.2 months in the Lynparza group compared to 4.3 months in the placebo group. The subgroup of BRCA-mutation patients represents the target clinical population. Also, exploratory efficacy analyses suggested that Lynparza maintenance treatment significantly delayed the time to the start of the next chemotherapy, and treatment benefit persisted past the first subsequent therapy. Although the submitted results did not suggest a detrimental effect on the overall survival (OS) in the subgroup of patients with BRCA mutation treated with Lynparza, the interim OS analysis failed to show a statistically significant difference between the treatment groups. The impact of Lynparza maintenance treatment on the quality of life (QoL) of patients was unclear. Nevertheless, the improved PFS observed with Lynparza in the BRCA-mutated subgroup is considered to predict clinical benefit in this group of patients. However, considering that the targeted population has a reduced tumor burden and is asymptomatic, the clinical benefit of maintenance therapy should preferably be confirmed by OS and/or QoL data. A Scientific Advisory Committee on Oncology Therapies meeting was held to seek advice on the clinical merit of Lynparza for the proposed indication. In summary, the Committee concluded that the benefit of prolonging PFS in the absence of an OS or QoL advantage outweighs the toxicity associated with Lynparza; however, the clinical benefit should preferably be confirmed with further study data.

Lynparza demonstrated an acceptable safety profile for the specified indication and appears to be well-tolerated. There were few dose modifications due to adverse drug reactions. The median duration of treatment was approximately 11 months in the BRCA-mutated subgroup.

The following adverse reactions were identified across clinical studies in patients with various solid tumours who received Lynparza 400 mg twice-daily monotherapy: nausea, vomiting, diarrhea, dyspepsia, fatigue, headache, dysgeusia, decreased appetite, dizziness, anemia, neutropenia, lymphopenia, mean corpuscular volume elevation, increase in blood creatinine, upper abdominal pain, stomatitis and thrombocytopenia. These adverse events were generally of grades 1 or 2 severity based on Common Terminology Criteria for Adverse Events (CTCAE).

The major safety issues associated with Lynparza included myelodysplastic syndrome/acute myeloid leukaemia, pneumonitis, and the potential for Lynparza to cause fetal harm when administered to a pregnant woman. These issues have been addressed through appropriate labelling in the Lynparza Product Monograph by highlighting them in a Serious Warnings and Precautions box.

A Risk Management Plan (RMP) for Lynparza was submitted by AstraZeneca Canada Inc. to Health Canada. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will be put in place to minimize risks associated with the product.

Health Canada reviewed the Look-alike Sound-alike Report submitted by the sponsor and accepted the proprietary name for the drug product.

Lynparza has an acceptable safety profile based on the non-clinical data and clinical studies. The identified safety issues can be managed through labelling and adequate monitoring. Appropriate warnings and precautions are in place in the Lynparza Product Monograph to address the identified safety concerns. As described within the framework of the NOC/c Guidance, safety monitoring on the use of Lynparza will be ongoing. Further evaluation will take place upon the submission of the requested studies after they become available.

Overall, the therapeutic benefits seen in the pivotal study are positive and the benefits of Lynparza therapy are considered to outweigh the potential risks. Lynparza was authorized under the NOC/c Guidance on the basis of the promising nature of the clinical evidence, and the need for further follow-up to confirm the clinical benefit.

This New Drug Submission complies with the requirements of sections C.08.002 and C.08.005.1 and therefore Health Canada has granted the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations. For more information, refer to the Clinical, Non-Clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.

3 What steps led to the approval of Lynparza?

A New Drug Submission for Lynparza was filed with Health Canada on March 16, 2015.

A Scientific Advisory Committee on Oncology Therapies meeting was held to seek advice on the clinical merit of Lynparza. The Committee considered that the benefit of prolonging progression-free survival, in the absence of an overall survival or quality of life advantage, outweighs the toxicity associated with Lynparza; however the clinical benefit should be preferably confirmed with further study data.

Subsequent review led to the decision to issue market authorization under the Notice of Compliance with Conditions (NOC/c) Guidance, in recognition of the promising but unconfirmed evidence of clinical effectiveness in the submission. In keeping with the provisions of the NOC/c Guidance, the sponsor agreed to provide additional information to confirm the clinical benefit.

Submission Milestones: Lynparza

Submission Milestone	Date
Pre-submission meeting:	2013-11-07
Submission filed:	2015-03-16
Screening 1
Screening Deficiency Notice issued:	2015-05-01
Response filed:	2015-05-11
Screening Acceptance Letter issued:	2015-06-04
Review 1
Oncology Therapies Scientific Advisory Committee meeting held:	2016-02-05
Biostatistics Evaluation complete:	2016-02-17
Biopharmaceutics Evaluation complete:	2016-03-15
Quality Evaluation complete:	2016-03-22
Clinical Evaluation complete:	2016-04-25
Labelling Review complete:	2016-04-12
Notice of Compliance with Conditions (NOC/c) Qualifying Notice issued:	2016-03-29
Response filed (Letter of Undertaking):	2016-04-01
Notice of Compliance (NOC) issued by Director General, Therapeutic Products Directorate under the Notice of Compliance with Conditions (NOC/c) Guidance:	2016-04-29

The Canadian regulatory decision on the non-clinical and clinical review of Lynparza was based on a critical assessment of the Canadian data package. The foreign reviews completed by the European Union's centralized procedure European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) were used as an added reference.

For additional information about the drug submission process, refer to the Management of Drug Submissions Guidance.

4 What follow-up measures will the company take?

As part of the marketing authorization for Lynparza, Health Canada requested and the sponsor agreed to several commitments to be addressed post-market. In addition to requirements outlined in the Food and Drugs Act and Regulations, AstraZeneca Canada Inc. has agreed to the following commitments which include (but are not limited to) providing the following reports to confirm the clinical benefit of Lynparza for the specified maintenance indication:

The report of the final overall survival analysis from Study D0810C00019 (Study 19).
The final study report of Study D0816C00002 (SOLO-2).

AstraZeneca Canada Inc. will also provide the results of targeted pharmacovigilance activities that are designed to effectively monitor the risk of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) in patients treated with Lynparza.

5 What post-authorization activity has taken place for Lynparza?

Summary Basis of Decision documents (SBDs) for eligible drugs authorized after September 1, 2012 will include post-authorization information in a table format. The Post-Authorization Activity Table (PAAT) will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decision was negative or positive. The PAAT will continue to be updated during the product's lifecycle.

The PAAT for Lynparza is found above.

For the latest advisories, warnings and recalls for marketed products, see MedEffect Canada.

6 What other information is available about drugs?

Up to date information on drug products can be found at the following links:

See MedEffect Canada for the latest advisories, warnings and recalls for marketed products.
See the Notice of Compliance (NOC) Database for a listing of the authorization dates for all drugs that have been issued an NOC since 1994.
See the Drug Product Database (DPD) for the most recent Product Monograph. The DPD contains product-specific information on drugs that have been approved for use in Canada and have been market notified (that is, the company has told Health Canada the product is being marketed).
See the Notice of Compliance with Conditions (NOC/c)-related documents for the latest fact sheets and notices for products which were issued an NOC under the Notice of Compliance with Conditions (NOC/c) Guidance Document, if applicable. Clicking on a product name links to (as applicable) the Fact Sheet, Part III: Patient Medication Information, Qualifying Notice, and Dear Health Care Professional Letter.
See the Patent Register for patents associated with medicinal ingredients, if applicable.
See the Register of Innovative Drugs for a list of drugs that are eligible for data protection under C.08.004.1 of the Food and Drug Regulations, if applicable.

7 What was the scientific rationale for Health Canada's decision?

7.1 Clinical Basis for Decision

Clinical Pharmacology

Olaparib, the medicinal ingredient of Lynparza, is a selective inhibitor of human poly (ADP-ribose) polymerase enzymes (PARP).

Olaparib is predominantly metabolized by the cytochrome P450 (CYP) enzyme CYP3A and therefore co-administered CYP3A inhibitors or inducers may respectively increase or decrease olaparib plasma concentration. In vitro, olaparib is an inhibitor of CYP3A4 and an inducer of CYP2B6. Olaparib is also a substrate and inhibitor of the transporter protein Multidrug Resistance Protein 1 (p-glycoprotein), hepatic uptake transporters, and renal uptake transporters which makes it a drug prone to many potential interactions. There is also a possible prolongation and potentiation of myelosuppressive toxicity when other myelosuppressive anti-cancer agents are co-administered with olaparib. A list of established or potential drug-drug interactions is included in the Lynparza Product Monograph.

The safety and efficacy of olaparib in patients with hepatic impairment have not been established. Olaparib is extensively metabolized by the liver and its metabolites excreted in the bile. The exposure to olaparib may be increased in patients with hepatic insufficiency compared to patients with normal hepatic functions, which may potentially lead to increased toxicity.

The safety and efficacy of olaparib in patients with moderate or severe renal impairment have not been established. Olaparib and its metabolites are extensively excreted in the urine. The exposure to olaparib may be increased in patients with moderate or severe renal insufficiency compared to patients with normal renal functions, which may potentially lead to increased toxicity.

The key clinical pharmacology findings are included in Lynparza Product Monograph. Uncertainties regarding the pharmacokinetics of olaparib are explicitly labelled in the Lynparza Product Monograph with recommendations for caution, where applicable. Furthermore, the sponsor has agreed to address these uncertainties via submissions following the market authorization of Lynparza. Overall, the clinical pharmacology evidence is considered acceptable.

For further details, please refer to the Lynparza Product Monograph, approved by Health Canada and available through the Drug Product Database.

Clinical Efficacy

The clinical efficacy of Lynparza (olaparib) as maintenance therapy in the treatment of platinum-sensitive relapsed (PSR), high-grade serous ovarian, fallopian tube, and primary peritoneal cancer patients, following treatment with two or more platinum-containing regimens, was studied in a Phase II randomized, double-blind, placebo-controlled study (Study 19). This pivotal study compared the efficacy of Lynparza 400 mg twice daily maintenance treatment with placebo maintenance treatment. The treatments were administered until disease progression. The study randomized 265 PSR ovarian cancer patients who were in complete response (CR) or in partial response (PR) to their last platinum-containing chemotherapy (136 patients in the Lynparza group and 129 patients in the placebo group).

The primary endpoint was progression-free survival (PFS) based on investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Secondary efficacy endpoints included overall survival (OS), disease control rate (DCR; defined as confirmed CR/PR + stable disease), health-related quality of life (QoL), and disease related symptoms. The primary endpoint, PFS, and the secondary endpoints, such as OS and QoL, are relevant for the proposed maintenance indication. Overall survival is the gold standard primary efficacy endpoint for clinical studies in ovarian cancer. Progression-free survival may be an acceptable endpoint in the maintenance settings when measured appropriately.

Only PSR patients who were in response following completion of their last platinum-based chemotherapy and whose disease had recurred >6 months after completion of prior penultimate platinum-based chemotherapy were enrolled. Patients could not have received prior treatments of Lynparza or other PARP inhibitor treatment. Patients could have received prior bevacizumab, except in the regimen immediately prior to randomization.

Breast cancer gene (BRCA) mutation status was determined in 96% (254 out of 265 patients) of the overall patient population. A BRCA mutation (BRCAm, germline and/or somatic) was detected in 136 patients; 74 were in the Lynparza group and 62 were in the placebo group.

Subgroup analyses demonstrated that patients with a BRCAm received the greatest PFS benefit from treatment with Lynparza maintenance therapy (hazard ratio [HR] 0.18; 95% confidence interval [CI] 0.10, 0.31; p<0.00001), with a statistically significant and clinically meaningful improvement in median PFS of 6.9 months over placebo. The median PFS was 11.2 months in the Lynparza group compared to 4.3 months in the placebo group.

Exploratory analysis of time to first subsequent therapy or death (TFST) suggests that Lynparza significantly delays the time to the start of next chemotherapy. Exploratory analysis of time to second subsequent therapy or death (TSST) suggests that the treatment benefit provided by Lynparza maintenance treatment persists past first subsequent therapy and continues onto second subsequent therapy. These results are promising, but due to the exploratory nature of these analyses, the impact of Lynparza on the efficacy of subsequent therapies is uncertain at this point.

Although the submitted results did not suggest a detrimental effect on the overall survival (OS) in the subgroup of patients with BRCAm treated with Lynparza, the interim OS analysis failed to show a statistically significant difference between the treatment groups (HR = 0.73, 95% CI: 0.45, 1.17; p = 0.19175).

The impact of Lynparza maintenance treatment on the QoL of patients was unclear.

A statistically significant, but smaller, treatment benefit in terms of prolongation of PFS was also observed for Lynparza maintenance treatment in patients who did not harbour a BRCAm (that is [i.e.], wildtype or patients with a variant of unknown significance), but the magnitude of the treatment benefit observed was smaller (PFS HR 0.54; 95% CI 0.34, 0.85; p = 0.007). However, in this subgroup of patients, there was no difference in OS between the treatment groups (HR 0.99; 95% CI 0.63, 1.55; p = 0.95724). Whilst the most well-described predictors of homologous recombination deficiency (HRD) are mutations or rearrangements in the BRCA gene, there are other non-BRCA mechanisms leading to HRDs, including mutations in other genes important in the HRD pathway, or other mechanisms including epigenetic silencing, which as yet cannot be readily identified clinically. This may explain some of the PFS benefit identified in the BRCA wild-type/variant of unknown significance subpopulation. However, there is likely a majority population within the wild-type population who will not derive treatment benefit from Lynparza. Therefore, until such time as testing allows the prospective identification of additional responders and non-responders within the wild-type population, Study 19 data is considered to support a maintenance indication in patients with BRCAm ovarian cancer.

In the pivotal study, the number of patients who had fallopian tube cancer (2.3%) or peritoneal cancer (11.3%) was not large. These low proportions were expected since fallopian tube cancer and primary peritoneal cancer are less common than epithelial ovarian carcinomas. Ovarian, fallopian tube, and primary peritoneal cancer form in the epithelial tissue covering the ovary, fallopian tube, or peritoneum. They share similar etiology, classification, pathophysiology and clinical characteristics and are all currently managed in a similar manner, regardless of the site of origin. They also have similar responses to anti-cancer treatment. The inclusion of patients with fallopian tube or primary peritoneal cancer in the targeted clinical population of the Lynparza indication is justified.

A supporting Phase II study (Study 41) also provided efficacy data. In Study 41, 162 patients were randomized, but only 25% of the study population had a known BRCAm. Using the overall population set, PFS was improved in the Lynparza group (HR = 0.51, 95%CI: 0.34, 0.77; p = 0.0012). As in the pivotal study, the greatest PFS benefit from the Lynparza treatment was observed in the subgroup of BRCAm patients (PFS HR 0.21; 95% CI 0.08, 0.55; p = 0.0015; median not reached in the Lynparza group versus [vs.] 9.7 months in the comparator group). The improvement in PFS appeared to be driven by a separation in the Kaplan-Meier curves after approximately 7 months, that is, during the maintenance phase. This data supports the PFS improvement associated with Lynparza that was observed in the pivotal study. However, as in the pivotal study, the final OS analysis of Study 41 failed to detect a statistically significant difference between the treatment groups in the overall population (HR = 1.17; 95% CI: 0.79, 1.73; p = 0.4379). Post-hoc OS analysis also did not show any statistical differences between the study groups in the BRCAm subgroup (HR: 1.28; 95% CI: 0.39, 4.18; p = 0.6861). As in the pivotal study, the results of Study 41 suggest that the treatment effect for PFS may be maintained in patients with BRCAm beyond the first progression, as demonstrated by the improved TSST in the Lynparza group. However, there is no data indicating that this benefit translates in an improvement of OS in the subgroup of patients with BRCAm. Finally, the impact of Lynparza on the QoL of patients from Study 41 is unknown since it was not assessed.

The sponsor provided an analysis of pooled efficacy and safety data to support Lynparza as monotherapy for patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. However, during the review of the data, a number of uncertainties surfaced regarding the methodology by which the efficacy data were obtained and the robustness of the responses. The current efficacy data provided within this submission is not considered to be sufficiently robust to recommend Lynparza in the fourth-line treatment setting for ovarian cancer.

Overall, the efficacy data presented in support of Lynparza for the maintenance treatment of patients with platinum-sensitive relapsed BRCAm ovarian cancer is promising. The improved PFS observed in the Lynparza group of the BRCAm subgroup of patients is considered to reasonably predict clinical benefit in this group of patients. However, there are limitations to these Phase II data as the PFS improvement in the maintenance setting has not been associated with an OS or a QoL advantage. Considering that the targeted population has an already reduced tumour burden and is asymptomatic, the clinical benefit of maintenance therapy needs to be confirmed.

Lynparza was issued marketing authorization with conditions, pending the results of studies to verify its clinical benefit. In order to confirm the clinical benefit of Lynparza for the specified maintenance indication, Health Canada deems it to be important to review the final OS analysis from Study 19. In addition, the sponsor has an ongoing Phase III clinical study (SOLO-2) which could help confirm the efficacy and safety of Lynparza for the maintenance indication and targeted clinical population.

Indication

The New Drug Submission for Lynparza was filed with the following two indications.

Lynparza (olaparib) is indicated as:

monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous ovarian cancer (including fallopian tube or primary peritoneal) who are in response (complete response or partial response) to platinum-based chemotherapy.
Platinum sensitivity is defined as disease progressing at least 6 months after completion of the penultimate platinum chemotherapy.Treatment with Lynparza should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.

Due to a number of uncertainties in the submitted data, Health Canada authorized only one of the proposed indications. The benefit/risk assessment for Lynparza as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy was found to be not acceptable for market authorization based on the efficacy and safety data provided within the submission.

The final recommended indication is as follows:

Lynparza (olaparib) is indicated as:

monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

Platinum sensitivity is defined as disease progressing at least 6 months after completion of the penultimate platinum chemotherapy.

For more information, refer to the Lynparza Product Monograph, approved by Health Canada and available through the Drug Product Database.

Clinical Safety

The overall clinical development program for Lynparza included 3,020 patients with a variety of solid tumours exposed at various doses.

The safety profile of Lynparza 400 mg twice daily maintenance monotherapy was most clearly defined in the pivotal study, Study 19, a randomized, double-blind, placebo-controlled study (described in the Clinical Efficacy section). In Study 19, 136 patients received Lynparza treatment while 128 received placebo. Supportive safety data were derived from the maintenance phase of the supporting study, Study 41. Additional safety data were obtained from pooled data from 766 patients with various solid tumours who received Lynparza 400 mg twice daily monotherapy in 12 Phase I and II monotherapy studies including a subset of 398 patients with BRCA-mutated ovarian cancer.

In Study 19, the most commonly reported adverse events (AEs) in Lynparza-treated patients as compared to placebo were nausea (71% vs. 36%), fatigue (52% vs. 39%), vomiting (35% vs. 14%), diarrhea (27% vs. 24%), abdominal pain (25% vs. 27%), and anemia (21% vs. 6%). Other common AEs also reported with at least a 5% greater frequency in the Lynparza group compared with the placebo group included: constipation (21% vs. 11%), decreased appetite (21% vs. 13%), headache (21% vs. 13%), abdominal pain upper (18% vs. 9%), cough (18% vs. 10%), dyspepsia (18% vs. 9%), back pain (17% vs. 11%), dysgeusia (16% vs. 6%), dizziness (14% vs. 7%), dyspnea (13% vs. 6%), upper respiratory tract infection (13% vs. 6%), and urinary tract infection (11% vs. 6%). These common AEs were generally of grade 1 or grade 2 severity.

Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 events were reported in 41% of Lynparza-treated patients and 22% of placebo-treated patients in Study 19. The CTCAE grade ≥3 events in the Lynparza group were mainly due to fatigue (8.1%), anaemia (5.1%), and neutropenia (3.7%) with most CTCAE grade ≥3 events overall related to the gastrointestinal, and blood and lymphatic systems. Serious AEs were reported in 18% of Lynparza-treated patients (mainly gastrointestinal [6%] and blood and lymphatic system [4%] related) and 9% of placebo-treated patients. The only serious AEs reported in more than 1 patient treated with Lynparza were anaemia (3 patients), and pancytopaenia, constipation, small intestinal obstruction and dyspnea (2 patients each).

The most common AEs leading to dose reduction were nausea, fatigue, vomiting, and anemia. Lynparza treatment was discontinued due to AEs in 6 (4.4%) of patients compared with 2 (1.6%) of patients receiving placebo. Events leading to Lynparza discontinuation were anaemia, neutropaenia, and thrombocytopaenia (each 0.4%); nausea (0.7%); and vomiting (0.5%).

Safety data from the maintenance phase of supportive Study 41 was consistent with the AE profile from Study 19.

The major safety issues associated with Lynparza include the following:

Myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML) - A small number of cases have been reported across the clinical development programme, including Study 19, the majority of which have been fatal. Based on evidence currently available, it is not possible to exclude the contribution of Lynparza to the development or acceleration of MDS/AML. MDS/AML is listed as an important potential risk in the Risk Management Plan and is labelled in the Serious Warnings and Precautions box of the Lynparza Product Monograph.
Pneumonitis - Rare cases have been reported across the Lynparza clinical development programme, some with fatal outcome. Pneumonitis is listed as an Important Potential Risk in the Risk Management Plan and is labelled in the Serious Warnings and Precautions box in the Lynparza Product Monograph.
Embryofoetal toxicity - This risk has been postulated based on preclinical studies. Embryofoetal toxicity is listed as an important potential risk in the Risk Management Plan and is labelled in the Serious Warnings and Precautions box due to potential exposure of Lynparza in women of childbearing potential.
Hematologic toxicity - Anemia was reported most commonly with decreases in neutrophils, lymphocytes and platelets also reported. Monthly monitoring of complete blood counts is recommended for the first 12 months and periodically after this time.
Patients with renal and hepatic impairment - The effect of renal and hepatic impairment on the pharmacokinetics of olaparib, the medicinal ingredient of Lynparza, and resultant safety and efficacy effects have not been studied. Lynparza is not recommended for patients with moderate or severe renal impairment or hepatic impairment (that is [i.e.] a serum bilirubin >1.5 times the upper limit of normal [ULN] or aspartate aminotransferase/alanine aminotransferase >2.5 times the ULN [>5 times the ULN in the presence of liver metastases]). Dedicated renal and hepatic impairment studies are being conducted with the tablet formulation of olaparib and will be reviewed by Health Canada when available.
New primary malignancies (other than MDS/AML) - The Risk Management Plan lists new primary malignancies as an important potential risk. Olaparib impairs the repair of damaged deoxyribonucleic acid (DNA). Patients with BRCAm have a deficiency in DNA repair. For these reasons, patients may be at increased risk for new malignancies. However, the incidence of new malignancies following olaparib exposure across the clinical development programme did not appear to be increased based on reference incidences in the literature.

In general, the safety profile of Lynparza is acceptable in the maintenance setting. However, as patients in the maintenance setting, may be treated for prolonged durations (for example [e.g.] 24 patients from Study 19 [18%] remained on Lynparza treatment at 3 years), ongoing pharmacovigilance is required to ensure long-term patient safety. As a Notice of Compliance with Conditions (NOC/c) has been recommended for Lynparza as maintenance therapy, the sponsor is required to submit to Health Canada annual Periodic Benefit Risk Evaluation Reports for 3 years (safety findings will be updated accordingly). The sponsor will also submit within 15 days individual case safety reports of all serious adverse reactions that occur in Canada and all serious unexpected adverse reactions that occur outside of Canada. Results of targeted pharmacovigilance activities which are designed to effectively monitor the risk of MDS/AML in patients treated with Lynparza will also be provided, as well as annual reports that monitor the risk of MDS/AML in patients treated with Lynparza. These documents will summarize all reports of MDS/AML including reports in clinical studies and post-marketing settings in order to evaluate long-term exposure to Lynparza treatment.

Overall, Lynparza has the potential to provide significant clinical benefits to patients with BRCA-mutated ovarian, fallopian tube, or primary peritoneal cancer. The clinical benefits outweigh the risks associated with Lynparza for the specified indication. Appropriate warnings and precautions are in place in the approved Lynparza Product Monograph to address the identified safety concerns.

For more information, refer to the Lynparza Product Monograph, approved by Health Canada and available through the Drug Product Database.

7.2 Non-Clinical Basis for Decision

The non-clinical profile (pharmacology and toxicology) of olaparib, the medicinal ingredient of Lynparza, has been adequately characterized. Olaparib demonstrated selective inhibition of poly ADP-ribose polymerase enzymes (PARP-1, PARP-2 and PARP-3) in biochemical and cellular assays. In particular, cell lines with deficiencies in BRCA function were sensitive to olaparib treatment. This in vitro activity translated into significant tumour regression and/or tumour growth delay in BRCA deficient animal models. In vivo efficacy was dose-dependent and correlated with the pharmacodynamic inhibition of PARP.

The key toxicological findings demonstrate that olaparib is myelotoxic, genotoxic, teratogenic, embryotoxic, and potentially carcinogenic. These toxicities have the potential to cause serious harm in humans at clinical exposures. For the safe and efficacious use of olaparib, these toxicities have been adequately labelled in the final Lynparza Product Monograph. The results of the non-clinical studies as well as the potential risks to humans have been included in the Lynparza Product Monograph.

In view of the intended use of Lynparza, there are no pharmacological/toxicological issues within this submission which preclude authorization of the product.

For more information, refer to the Lynparza Product Monograph, approved by Health Canada and available through the Drug Product Database.

7.3 Quality Basis for Decision

The Chemistry and Manufacturing information submitted for Lynparza has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications. Proper development and validation studies were conducted, and adequate controls are in place for the commercial processes. Changes to the manufacturing process and formulation made throughout the pharmaceutical development are considered acceptable upon review. Based on the stability data submitted, the proposed shelf-life of 24 months is acceptable when the product is stored at 2°C-25°C.

Proposed limits of drug-related impurities are considered adequately qualified (that is, within International Council for Harmonisation [ICH] limits and/or qualified from toxicological studies).

All sites involved in production are compliant with Good Manufacturing Practices.

All non-medicinal ingredients (excipients) found in the drug product are acceptable for use in drugs according to the Food and Drug Regulations.

Olaparib (the drug substance) and the materials used in the preparation of olaparib are not of human or animal origin. The excipients used in the drug product formulation are not of animal or human origin.

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Product name	DIN	Company name	Active ingredient(s) & strength
LYNPARZA	02475200	ASTRAZENECA CANADA INC	OLAPARIB 100 MG
LYNPARZA	02475219	ASTRAZENECA CANADA INC	OLAPARIB 150 MG

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