Summary Basis of Decision for Byooviz
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:
Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for Byooviz is located below.
Recent Activity for Byooviz
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.
Summary Basis of Decision (SBD) for Byooviz
Date SBD issued: 2022-08-12
The following information relates to the new drug submission for Byooviz.
Ranibizumab
Drug Identification Number (DIN):
- DIN 02525852 - 10 mg/mL ranibizumab, solution, intravitreal administration
Samsung Bioepis Co., Ltd.
New Drug Submission Control Number: 251162
On March 8, 2022, Health Canada issued a Notice of Compliance (NOC) to Samsung Bioepis Co., Ltd for Byooviz, a biosimilar to Lucentis (the reference biologic drug). The terms "biosimilar biologic drug" and "biosimilar" are used by Health Canada to describe subsequent entry versions of a Canadian approved innovator biologic drug with demonstrated similarity to a reference biologic drug. Biosimilars were previously referred to as subsequent entry biologics in Canada. Byooviz contains the medicinal ingredient ranibizumab, which has been demonstrated to be highly similar to ranibizumab contained in the reference biologic drug, Lucentis.
Authorization of a biosimilar means that the product is highly similar to the reference biologic drug in terms of quality and that there are no clinically meaningful differences in efficacy and safety between the two products. The weight of evidence for similarity is provided by the structural and functional studies, whereas the non-clinical and clinical programs are designed to address potential areas of residual uncertainty. A final determination of similarity is based on the entire submission, including data derived from comparative structural, functional, non-clinical, pharmacokinetic and pharmacodynamic, and clinical studies.
The demonstration of similarity between the biosimilar and its reference biologic drug enables the sponsor's submission for the biosimilar to rely on the safety and efficacy information of the reference biologic drug in the indications being sought.
For more information on the authorization of biosimilars, refer to the Health Canada website on Biosimilar Biologic Drugs.
In this drug submission, Lucentis is the reference biologic drug. Similarity between Byooviz and Lucentis was established in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document. When filing the submission for Byooviz, the sponsor requested authorization for all of the indications that had been authorized for Lucentis at the time.
The market authorization was based on the quality (chemistry and manufacturing) package submitted, as well as demonstrated similarity between the biosimilar and the reference biologic drug. Similarity was established through data derived from comparative structural and functional studies to establish quality attributes. To support the clinical comparability of Byooviz and Lucentis, the sponsor submitted results from a Phase III randomized, double-blind, parallel-group, multicentre study SB11‑G31‑AMD. This study compared the efficacy, safety, pharmacokinetics, and immunogenicity between Byooviz and Lucentis in patients with neovascular age‑related macular degeneration. For the sought indications other than age‑related macular degeneration, extrapolation of data was used to support these indications given the same mechanism of action of ranibizumab in the target conditions.
Based on Health Canada’s review, the benefit‑risk profile of Byooviz is considered to be similar to the benefit-risk profile of the reference biologic drug, and is therefore considered favourable for the treatment of the following conditions:
- neovascular (wet) age-related macular degeneration;
- visual impairment due to diabetic macular edema;
- visual impairment due to macular edema secondary to retinal vein occlusion;
- visual impairment due to choroidal neovascularization secondary to pathologic myopia;
- visual impairment due to choroidal neovascularization secondary to ocular conditions other than age-related macular degeneration or pathologic myopia, including but not limited to angioid streaks, post-inflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy.
1 What was approved?
Byooviz, an anti‑neovascularization agent, was authorized for the treatment of:
- neovascular (wet) age-related macular degeneration;
- visual impairment due to diabetic macular edema;
- visual impairment due to macular edema secondary to retinal vein occlusion;
- visual impairment due to choroidal neovascularization secondary to pathologic myopia;
- visual impairment due to choroidal neovascularization secondary to ocular conditions other than age-related macular degeneration or pathologic myopia, including but not limited to angioid streaks, post- inflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy.
Byooviz is not authorized for use in pediatric patients (younger than 18 years of age), as very limited clinical efficacy and safety data are currently available for this population.
No overall differences in efficacy or safety were observed in geriatric patients (65 years of age and older) compared to those younger than 65 years of age in clinical trials.
Byooviz is a biosimilar to Lucentis. Both drugs contain the medicinal ingredient, ranibizumab. Ranibizumab is a humanized recombinant monoclonal antibody fragment that targets human vascular endothelial growth factor‑A (VEGF‑A). Ranibizumab is designed to penetrate all retinal layers and to bind with high affinity to all active VEGF‑A isoforms (e.g., VEGF110, VEGF121, and VEGF165), thereby preventing the binding of VEGF‑A to its receptors VEGFR‑1 and VEGFR‑2. Vascular endothelial growth factor‑A is a protein that promotes the growth of new blood vessels. Binding of VEGF‑A to its receptors leads to endothelial cell proliferation and neovascularization, as well as vascular leakage. Increased levels of VEGF in the ocular fluids or retinal pigment epithelium have been implicated in the pathogenesis of neovascular (wet) form of age‑related macular degeneration, choroidal neovascularization, diabetic macular edema, and diabetic retinopathy. By inhibiting the binding of VEGF‑A to its receptors, ranibizumab reduces the growth of blood vessels and controls leakage and swelling in the eye.
Similarity between Byooviz and the reference biologic drug, Lucentis, has been established on the basis of comparative structural and functional studies, and a comparative efficacy, safety, immunogenicity, and pharmacokinetic Phase III study (SB11‑G31-AMD) in patients with neovascular age‑related macular degeneration, in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document. For the sought indications other than age‑related macular degeneration, the mechanism of action of ranibizumab is known to be the same (i.e., binding to the receptor-binding site of active forms of VEGF‑A) and, accordingly, the use of data extrapolation to support these additional indications is justified.
Byooviz (10 mg/mL ranibizumab) is supplied in a single‑use vial as a solution for injection. Each vial contains 0.23 mL solution and 2.3 mg of ranibizumab. This provides an extractable amount to deliver a single‑dose of 0.05 mL containing 0.5 mg ranibizumab. In addition to the medicinal ingredient, the solution contains the following non‑medicinal ingredients: α, α‑trehalose dihydrate, histidine hydrochloride monohydrate, histidine, polysorbate 20, and water for injection.
The use of Byooviz is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container, patients with active or suspected ocular or periocular infections, and patients with active intraocular inflammation.
The drug product was approved for use under the conditions stated in its Product Monograph taking into consideration the potential risks associated with its administration. The Byooviz Product Monograph is available through the Drug Product Database.
For more information about the rationale for Health Canada's decision, refer to the Quality (Chemistry and Manufacturing), Non-clinical, and Clinical Basis for Decision sections.
2 Why was Byooviz approved?
Based on Health Canada's review, the benefit‑risk profile of Byooviz is considered to be similar to that of the reference biologic drug, and is therefore considered favourable for the treatment of:
- neovascular (wet) age-related macular degeneration;
- visual impairment due to diabetic macular edema;
- visual impairment due to macular edema secondary to retinal vein occlusion;
- visual impairment due to choroidal neovascularization secondary to pathologic myopia;
- visual impairment due to choroidal neovascularization secondary to ocular conditions other than age-related macular degeneration or pathologic myopia, including but not limited to angioid streaks, post- inflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy.
Similarity between Byooviz and Lucentis was established in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.
Byooviz is considered to be biosimilar to Lucentis. Lucentis is authorized and marketed in Canada for several indications and clinical uses. The specific diseases or conditions for which Lucentis was authorized at the time when the Byooviz submission was filed included: neovascular (wet) age‑related macular degeneration; diabetic macular edema; macular edema secondary to retinal vein occlusion; choroidal neovascularization secondary to pathologic myopia; and choroidal neovascularization secondary to ocular conditions other than age‑related macular degeneration or pathologic myopia, including but not limited to angioid streaks, post‑inflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy. The New Drug Submission filed for Byooviz requested authorization for all of the aforementioned indications and clinical uses.
Based on comparative structural and functional studies, Byooviz and Lucentis were judged to be highly similar in terms of quality attributes. To support the clinical comparability of Byooviz and Lucentis, the sponsor submitted results from a Phase III, randomized, double-blind, parallel-group, multicentre study SB11‑G31‑AMD. This study compared the efficacy, safety, pharmacokinetics, and immunogenicity between Byooviz and Lucentis in patients with neovascular age‑related macular degeneration. For the sought indications other than age‑related macular degeneration, extrapolation of data was used to support these indications given the same mechanism of action of ranibizumab in the target conditions.
Byooviz has demonstrated a comparable safety profile to its reference product, Lucentis. Therefore, the Adverse Reactions section of the biosimilar Product Monograph is based on the clinical experience with the reference biologic drug.
A Risk Management Plan (RMP) for Byooviz was submitted by Samsung Bioepis Co., Ltd 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.
The submitted inner and outer labels, package insert, and Patient Medication Information section of the Byooviz Product Monograph meet the necessary regulatory labelling, plain language, and design element requirements.
The sponsor submitted a brand name assessment that included testing for look‑alike sound‑alike attributes. Upon review, the proposed name Byooviz was accepted.
Overall, the benefits of Byooviz therapy are expected to be similar to the known benefits of the reference biologic drug, Lucentis, and are considered to outweigh the potential risks. The identified safety issues can be managed through labelling and adequate monitoring. Appropriate warnings and precautions are in place in the Byooviz Product Monograph to address the identified safety concerns.
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 Quality (Chemistry and Manufacturing), Non-clinical, and Clinical Basis for Decision sections.
3 What steps led to the approval of Byooviz?
The Canadian regulatory decision regarding Byooviz was based on a critical assessment of the data package submitted to Health Canada. The foreign review completed by the United States Food and Drug Administration (FDA), as well as relevant FDA correspondence were also consulted during the review.
For additional information about the drug submission process, refer to the Management of Drug Submissions and Applications Guidance.
Submission Milestones: Byooviz
| Submission Milestone | Date |
|---|---|
| Pre-submission meeting | 2021-01-18 |
| New Drug Submission filed | 2021-03-29 |
| Screening | |
| Screening Acceptance Letter issued | 2021-05-12 |
| Review | |
| Review of Risk Management Plan completed | 2022-01-25 |
| Quality evaluation completed | 2022-02-22 |
| Clinical/medical evaluation completed | 2022-03-02 |
| Labelling review completed | 2022-03-07 |
| Notice of Compliance issued by Director General, Biologic and Radiopharmaceutical Drugs Directorate | 2022-03-08 |
4 What follow-up measures will the company take?
Requirements for post-market commitments are outlined in the Food and Drugs Act and Regulations.
The onus is on the Byooviz sponsor to monitor the post-market safety profile of this biosimilar as well as the Product Monograph of the reference biologic drug for safety signals that could impact the biosimilar, and make safety updates to the Byooviz Product Monograph as appropriate. New safety issues that are first identified with the biosimilar, the reference biologic drug, or other biologics that share a common medicinal ingredient may or may not have relevance to both the biosimilar and the reference biologic drug. For more information, refer to the Fact Sheet: Biosimilars.
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.
- 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, 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 Quality Basis for Decision
Byooviz was developed as a biosimilar to the reference biologic drug, Lucentis. For biosimilars, the weight of evidence is provided by structural and functional studies. Biosimilars are manufactured to the same regulatory standards as other biologic drugs. In addition to a typical chemistry and manufacturing data package that is submitted for a standard new biologic drug, biosimilar submissions include extensive data demonstrating similarity with the reference biologic drug.
Comparative Structural and Functional Studies
Byooviz was developed to match the strength and product characteristics of Lucentis sourced from the United States market (hereafter referred to as US‑Lucentis). US‑Lucentis is considered a suitable proxy for the Canadian reference biologic drug, as it meets the requirements set forth in the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document. The products that were authorized in the European Union (EU‑Lucentis) and Korea (KR-Lucentis) were also used in the similarity evaluation.
A comprehensive panel of tests was conducted to evaluate the physicochemical, biological, purity and impurity, and stability profiles of the drug products. Statistical quality ranges for similarity assessment were defined based on product attribute criticality. The overall approach applied was acceptable, and the results of the studies demonstrated that Byooviz and Lucentis are identical in terms of the primary structure and highly similar in terms of the higher-order structure, purity, and biological activities. Comparative forced degradation studies using different stress conditions generated similar degradation profiles for Byooviz, US-Lucentis, and EU-Lucentis. Together, these results support that Byooviz is highly similar to Lucentis and meet the quality requirements for Byooviz to be considered a biosimilar to Lucentis.
Characterization of the Drug Substance
Ranibizumab (the medicinal ingredient in Byooviz) is a humanized recombinant monoclonal antibody fragment that binds to human vascular endothelial growth factor A (VEGF‑A). The monoclonal antibody fragment is designed to bind with high affinity to all active VEGF‑A isoforms (e.g., VEGF110, VEGF121 and VEGF165), thereby preventing the binding of VEGF‑A to its receptors VEGFR‑1 and VEGFR‑2. Vascular endothelial growth factor‑A is a protein that promotes the growth of new blood vessels. When VEGF‑A binds to its receptors, it induces endothelial cell proliferation and neovascularization, as well as vascular leakage. Increased levels of VEGF in the ocular fluids and retinal pigment epithelium have been implicated in the pathogenesis of neovascular (wet) form of age-related macular degeneration, choroidal neovascularization, diabetic macular edema, and diabetic retinopathy. By inhibiting the binding of VEGF‑A to its receptors, ranibizumab reduces the growth of blood vessels and controls leakage and swelling in the eye.
Detailed characterization studies were performed to provide assurance that ranibizumab consistently exhibits the desired characteristic structure and biological activity.
Results from process validation studies indicate that the processing steps adequately control the levels of product- and process-related impurities. The impurities that were reported and characterized were found to be within established and acceptable limits.
Manufacturing Process of the Drug Substance and Drug Product and Process Controls
The drug substance, ranibizumab (also referred to as SB11), is a humanized immunoglobulin G1 kappa isotype (IgG1κ) monoclonal antibody Fab fragment produced by recombinant deoxyribonucleic acid technology.
The drug substance manufacturing process is initiated with the thawing of a vial of cells from a working cell bank which is an Escherichia coli strain transfected with SB11 expression vector. After thawing, the cells are expanded in multiple steps until sufficient cells are obtained to inoculate the fed‑batch production bioreactors. As the cell culture expands, the recombinant protein is expressed and secreted into the culture medium. Subsequently, the cell culture fluid is harvested and purified through a series of chromatographic and filtration steps. The resulting product is concentrated and diafiltered into formulation buffer. The final drug substance is filtered, dispensed into polycarbonate bottles, and stored frozen.
The drug product manufacturing process consists of thawing the drug substance, bioburden reduction filtration, pooling, mixing, sterile filtration, and aseptic filling into glass vials. The vials are then stoppered, capped, visually inspected, and packaged.
Process validation was conducted with nine consecutive drug substance batches and three consecutive drug product batches manufactured at the intended commercial scale. Process performance qualification data demonstrate that the manufacturing process is capable of consistently manufacturing drug substance and drug product of adequate quality. All process parameters, process attributes, release testing results, and stability results met predefined criteria, acceptance limits, and specifications for all process validation lots. All process validation studies were deemed successful and supportive of hold times, impurity clearance, resin/membrane lifetimes, filters, extractables and leachables content, shipping, and other supporting activities and equipment.
None of the non-medicinal ingredients (excipients, described earlier) found in the drug product are prohibited by the Food and Drug Regulations. The compatibility of ranibizumab with the excipients is supported by the stability data provided.
Control of the Drug Substance and Drug Product
The control strategy for Byooviz consists of in‑process control of product quality attributes, control of process parameters, control of process performance, product characterization testing, product control through quality attribute release and stability testing, control of materials, and facility and equipment controls. This multi‑level control strategy, as part of the overall process performance and product quality monitoring system, assures consistent manufacture of acceptable product and mitigates the risk of failures in process performance.
The proposed control strategy implements controls at appropriate manufacturing unit operations to ensure consistency of the process and product quality across all stages of manufacturing. Overall, the drug substance and drug product manufacturing processes are controlled by multiple process parameters, in‑process gateways, and in‑process tests with defined action ranges or in‑process specifications, depending on the criticality of the parameter. If the results are outside of the predefined in‑process specification or action range, the batch is rejected, or an evaluation of the deviation is performed, and the disposition decision is determined based on the outcome of the investigation.
All in‑house analytical methods were appropriately validated. The reference standards have been well characterized and an appropriate program is in place to qualify new primary and working reference material in the future. Each specification considers historical release and stability batch data, reference product ranges, clinical experience, manufacturing capability, assay variability, regulatory expectations, and compendial requirements for protein‑based products, where appropriate. The justifications for the acceptance criteria are based on the release and long‑term stability data of lots that are representative of the commercial process.
Stability of the Drug Substance and Drug Product
Based on the stability data submitted, the proposed shelf life and storage conditions for the drug substance and drug product were adequately supported and are considered to be satisfactory.
The stability data supports a shelf life of 36 months for the drug product, when stored at 2 °C to 8 °C and protected from light. Prior to use, the unopened vial may be stored at 30 °C ± 2 °C for a period up to one month. The product should not be frozen.
The compatibility of the drug product with the container closure system was demonstrated through compendial testing and stability studies. The container closure system met all validation test acceptance criteria.
The proposed packaging and components are considered acceptable.
Facilities and Equipment
Based on risk assessment scores determined by Health Canada, an on‑site evaluation (OSE) was recommended for the drug substance manufacturing site, whereas an OSE was not deemed necessary for the drug product manufacturing site.
The in‑person OSE for the drug substance manufacturing facility was cancelled due to the travel restrictions imposed in response to the coronavirus disease (COVID-19) pandemic. As a risk mitigation strategy for the inability to perform an in‑person OSE, additional documentation was requested and reviewed by Health Canada. The provided documentation was considered sufficient to support the final quality review recommendation.
Adventitious Agents Safety Evaluation
Byooviz drug substance is expressed in Escherichia coli. As bacterial systems do not support replication of mammalian viruses, viral clearance studies were not applicable.
7.2 Non-Clinical Basis for Decision
For biosimilars, the degree of similarity at the quality level determines the scope and the breadth of the required non-clinical data. Non-clinical studies serve to complement the structural and functional studies and address potential areas of residual uncertainty.
In vivo non‑clinical studies (e.g., primary/secondary pharmacodynamics, safety pharmacology) were not required for Byooviz. This is considered acceptable, provided that the comparability in quality attributes is demonstrated, in accordance with Health Canada's Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.
For more information, refer to the Byooviz Product Monograph, approved by Health Canada and available through the Drug Product Database.
7.3 Clinical basis for decision
The purpose of the clinical program for a biosimilar is to demonstrate that there are no clinically meaningful differences between the biosimilar and the reference biologic drug. The structural complexity of the biologic drug and availability of a relevant and sensitive pharmacodynamic endpoint determine the scope and the breadth of the required clinical data. The clinical program is designed to complement the structural and functional studies and address potential areas of residual uncertainty.
Comparative Pharmacokinetic and Pharmacodynamic Studies
A clinical Phase I pharmacokinetic study was not conducted since it is not considered meaningful to determine the biosimilarity based on the pharmacokinetic comparison of systemic exposure of Byooviz and Lucentis. The serum concentration of ranibizumab following intravitreal injection is negligible and variable. Furthermore, the conduct of a pharmacokinetic study in healthy volunteers is deemed unethical due to the invasiveness of intravitreal injections. To support the overall assessment of the systemic exposure of Byooviz relative to Lucentis, the pharmacokinetic profiles of Byooviz and Lucentis were evaluated in a subset of patients in the clinical Phase III comparative efficacy study, SB11-G31-AMD.
Of the 705 patients randomized in the SB11-G31-AMD study, 54 (7.7%) of patients (25 [7.1%] patients in the Byooviz treatment group and 29 [8.2%] patients in the Lucentis treatment group) were included in a pharmacokinetic analysis set. Overall, the demographic characteristics of the patients in the pharmacokinetic analysis set were comparable between the two treatment groups.
The pharmacokinetic data collected at all the post‑dose pharmacokinetic sampling time points showed that the arithmetic mean serum concentration ranged between 1.346 ng/mL and 1.952 ng/mL for Byooviz-treated patients and 0.771 ng/mL to 1.298 ng/mL for Lucentis-treated patients. The variability of post‑dose concentrations was high, 63.61% to 96.03% for Byooviz and 39.39% to 97.73% for Lucentis. The observed maximum concentrations from both treatment groups up to Week 52 were all below the ranibizumab concentration range necessary to inhibit the biological activity of vascular endothelial growth factor‑A (VEGF-A) by 50% (11 to 27 ng/mL, as assessed in an in vitro cellular proliferation assay).
For further details, please refer to the Byooviz Product Monograph, approved by Health Canada and available through the Drug Product Database.
Comparative Clinical Efficacy and Safety
The comparative clinical efficacy of Byooviz and its reference biologic drug Lucentis was evaluated in a Phase III, randomized, double-blind, parallel group, multicentre study SB11‑G31‑AMD. This study compared the efficacy, safety, pharmacokinetics, and immunogenicity between Byooviz and Lucentis in patients with neovascular age‑related macular degeneration.
Patients were randomly allocated in a 1:1 ratio to receive either 0.5 mg Byooviz or 0.5 mg Lucentis, administered into the study eye via intravitreal route every 4 weeks for up to Week 48. Patients received a total of 13 doses during the study and the last assessment occurred at Week 52. A total of 705 patients were randomized (number of patients [n] = 351 in the Byooviz arm and n = 354 in the Lucentis arm).
The primary endpoint was the change from baseline in best‑corrected visual acuity (BCVA) at Week 8. Best‑corrected visual acuity change from baseline to Week 24 and Week 52 were evaluated as secondary endpoints. All patients, with the exception of one in Lucentis arm who withdrew from the study due to adverse reaction, completed the study (n = 704).
Study results showed that the treatment difference of the changes from baseline in BCVA between Byooviz and Lucentis at Week 8 was ‑0.80 letters and the 95% confidence interval (CI) was (‑2.023, 0.415), which was contained within the predefined similarity margin of (‑3 letters, 3 letters).
As for the secondary endpoints, the changes in BCVA from baseline to Week 24 and Week 52 were also shown to be comparable (difference was ‑0.80 [95% CI: ‑2.314, 0.705] at Week 24 and ‑0.62 [95% CI: ‑2.375, 1.140] at Week 52).
The safety findings from the SB11‑G31‑AMD study were consistent with the safety profile previously reported for Lucentis. Similar important identified risks were noted, which include increases in intraocular pressure, infectious endophthalmitis, retinal detachments and retinal tear, and intraocular inflammation. Appropriate warnings and precautions are in place in the approved Byooviz Product Monograph to address the identified safety concerns, as is found in the Product Monograph for Lucentis.
Ranibizumab has not been studied in patients who have previously received other types of intravitreal injections. Ranibizumab should not be administered concurrently with other anti-VEGF agents (systemic or ocular).
Available data do not suggest an increased risk of systemic adverse events with bilateral treatment. The efficacy of ranibizumab therapy administered to both eyes concurrently has not been studied.
Ranibizumab has not been studied in patients with concurrent eye conditions such as retinal detachment or macular hole.
No clinical data concerning exposure to ranibizumab during human pregnancy are available. The systemic exposure to ranibizumab is low after ocular administration, but due to its mechanism of action, ranibizumab must be regarded as potentially teratogenic, embryotoxic and fetotoxic. Therefore, ranibizumab should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. For women who wish to become pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the last dose of ranibizumab before conceiving a child.
It is not known whether ranibizumab is excreted in human milk. As a precautionary measure, breastfeeding is not recommended during the use of ranibizumab.
Overall, the safety profile of Byooviz is considered to be comparable to that which has been established for the reference biologic drug Lucentis. The identified safety concerns are appropriately addressed in the Warnings and Precautions section of the Byooviz Product Monograph, as they are in the Product Monograph for Lucentis.
For more information, refer to the Byooviz Product Monograph, approved by Health Canada and available through the Drug Product Database.
Comparative Immunogenicity
The incidence of anti-drug antibody across the time points evaluated during the SB11‑G31‑AMD study was comparable between Byooviz and Lucentis treatment groups. At weeks 8, 24, and 52, anti-drug antibody positive rates were 2.4%, 3.0%, and 4.2% in Byooviz‑treated patients and 2.1%, 3.1%, and 5.5% in Lucentis‑treated patients, respectively. The type, frequency, and severity of adverse events (both ocular and non‑ocular adverse events) over the study course of 52 weeks did not show clinically meaningful differences between the Byooviz and Lucentis treatment groups.
Indications
Byooviz is considered to be biosimilar to Lucentis, the reference biologic drug. Lucentis is authorized and marketed in Canada for several indications and clinical uses. The specific conditions for which Lucentis is authorized are neovascular (wet) age‑related macular degeneration, diabetic macular edema, macular edema secondary to retinal vein occlusion, choroidal neovascularization secondary to pathologic myopia, and choroidal neovascularization secondary to ocular conditions other than age‑related macular degeneration or pathologic myopia, including but not limited to angioid streaks, post‑inflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy.
When filing the submission for Byooviz, the sponsor requested authorization for all of the indications that had been authorized for Lucentis at the time.
The sponsor provided an acceptable scientific rationale to support the request for authorization of each of the proposed indications in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.
Upon review of the submitted information, Byooviz has been authorized for the treatment of:
- neovascular (wet) age-related macular degeneration;
- diabetic macular edema;
- macular edema secondary to retinal vein occlusion;
- choroidal neovascularization secondary to pathologic myopia;
- choroidal neovascularization secondary to ocular conditions other than age-related macular degeneration or pathologic myopia, including but not limited to angioid streaks, post-inflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| BYOOVIZ | 02525852 | SAMSUNG BIOEPIS CO., LTD | RANIBIZUMAB 10 MG / ML |