Summary Basis of Decision for Elonox/Elonox HP

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

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

Recent Activity for Elonox/Elonox HP

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 Elonox/Elonox HP

Date SBD issued: 2023-03-28

The following information relates to the new drug submission for Elonox/Elonox HP.

Enoxaparin sodium

Drug Identification Number (DIN):

  • DIN 02532247 (Elonox) - 30 mg/0.3 mL (100 mg/mL) enoxaparin sodium, solution, intravenous or subcutaneous administration
  • DIN 02532255 (Elonox) - 40 mg/0.4 mL (100 mg/mL) enoxaparin sodium, solution, intravenous or subcutaneous administration
  • DIN 02532263 (Elonox) - 60 mg/0.6 mL (100 mg/mL) enoxaparin sodium, solution, intravenous or subcutaneous administration
  • DIN 02532271 (Elonox) - 80 mg/0.8 mL (100 mg/mL) enoxaparin sodium, solution, intravenous or subcutaneous administration
  • DIN 02532298 (Elonox) - 100 mg/mL enoxaparin sodium, solution, intravenous or subcutaneous administration
  • DIN 02532301 (Elonox HP) - 120 mg/0.8 mL (150 mg/mL) enoxaparin sodium, solution, intravenous or subcutaneous administration
  • DIN 02532328 (Elonox HP) - 150 mg/mL enoxaparin sodium, solution, intravenous or subcutaneous administration

Fresenius Kabi Canada Ltd.

New Drug Submission Control Number: 243026

On October 26, 2022, Health Canada issued a Notice of Compliance (NOC) to Fresenius Kabi Canada Ltd. for Elonox/Elonox HP, a biosimilar to Lovenox/Lovenox HP (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. Elonox/Elonox HP contains the medicinal ingredient enoxaparin sodium, which has been demonstrated to be highly similar to enoxaparin sodium contained in the reference biologic drug, Lovenox/Lovenox HP.

Authorization of a biosimilar means that it 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. To be considered a biosimilar, the weight of evidence is provided by the structural and functional studies; 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, Lovenox/Lovenox HP is the reference biologic drug. Similarity between Elonox/Elonox HP and Lovenox/Lovenox HP was established in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document. Within this drug submission, the sponsor requested the authorization of Elonox/Elonox HP for all of the indications that are currently authorized for Lovenox/Lovenox HP.

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, functional, non-clinical, and clinical studies. Based on Health Canada’s review, the benefit-risk profile of Elonox/Elonox HP is considered to be similar to the benefit-risk profile of the reference biologic drug, and is therefore considered favourable for the following indications:

  • The prophylaxis of thromboembolic disorders (deep vein thrombosis) in patients undergoing:
    • orthopedic surgery of the hip or knee. In addition, Elonox is indicated in hospital or after hospital discharge for long-term prevention of venous thromboembolic diseases following hip replacement surgery.
    • high risk abdominal, gynecological, or urological surgeries.
    • colorectal surgery.
  • The prophylaxis of deep vein thrombosis in medical patients who are at moderate risk of deep vein thrombosis and who are bedridden due to moderate to severe acute cardiac insufficiency (New York Heart Association [NYHA] class III or IV heart failure), acute respiratory failure revealing or complicating chronic respiratory insufficiency not requiring ventilatory support and acute respiratory infections (excluding septic shock), who require short-term prophylaxis of deep vein thrombosis.
  • The prevention of thrombus formation in the extracorporeal circulation during hemodialysis.
  • The treatment of deep vein thrombosis, with or without pulmonary embolism.
  • The treatment of unstable angina or non–Q–wave myocardial infarction, concurrently with acetylsalicylic acid.
  • The treatment of acute ST–segment elevation myocardial infarction, including patients to be managed medically or with subsequent percutaneous coronary intervention.

1 What was approved?

Elonox and Elonox HP are biosimilars to Lovenox and Lovenox HP (hereafter referred to as Elonox and Lovenox, respectively).

Elonox is an antithrombotic agent authorized for the following indications:

  • The prophylaxis of thromboembolic disorders (deep vein thrombosis) in patients undergoing:
    • orthopedic surgery of the hip or knee. In addition, Elonox is indicated in hospital or after hospital discharge for long-term prevention of venous thromboembolic diseases following hip replacement surgery.
    • high risk abdominal, gynecological, or urological surgeries.
    • colorectal surgery.
  • The prophylaxis of deep vein thrombosis in medical patients who are at moderate risk of deep vein thrombosis and who are bedridden due to moderate to severe acute cardiac insufficiency (New York Heart Association [NYHA] class III or IV heart failure), acute respiratory failure revealing or complicating chronic respiratory insufficiency not requiring ventilatory support and acute respiratory infections (excluding septic shock), who require short-term prophylaxis of deep vein thrombosis.
  • The prevention of thrombus formation in the extracorporeal circulation during hemodialysis.
  • The treatment of deep vein thrombosis, with or without pulmonary embolism.
  • The treatment of unstable angina or non–Q–wave myocardial infarction, concurrently with acetylsalicylic acid.
  • The treatment of acute ST–segment elevation myocardial infarction, including patients to be managed medically or with subsequent percutaneous coronary intervention.

Elonox is not authorized for use in pediatric patients (less than 18 years of age), as no data are available to Health Canada for this population.

Evidence from clinical studies and experience suggests that use in the geriatric population (75 years of age and older) is associated with differences in safety.

Both Elonox and the reference biologic drug, Lovenox, contain the medicinal ingredient enoxaparin sodium. Enoxaparin sodium is the sodium salt of enoxaparin, a mixture of low molecular weight fragments of heparin sodium obtained by alkaline depolymerization of the benzyl ester of heparin sodium. The heparin sodium is obtained from porcine intestinal mucosa.

Similarity between Elonox and the reference biologic drug, Lovenox, has been established on the basis of comparative structural and functional studies, comparative non-clinical studies, and a comparative pharmacokinetic and pharmacodynamic study in healthy adult male subjects, in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.

This biosimilar biologic drug is presented as a solution with two different concentrations: 100 mg/mL enoxaparin sodium (Elonox) and 150 mg/mL (high potency) enoxaparin sodium (Elonox HP). In addition to the medicinal ingredient, the solution contains water for injection.

The use of Elonox is contraindicated in:

  • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container, or to other low molecular weight heparins and/or heparin.
  • Patients with a history of confirmed or suspected immunologically-mediated heparin-induced thrombocytopenia (delayed-onset severe thrombocytopenia), within the past 100 days, or in patients in whom an in vitro platelet-aggregation test in the presence of enoxaparin is positive (circulating antibodies).
  • Patients with:
    • acute or subacute bacterial endocarditis.
    • active bleeding.
    • major blood clotting disorders.
    • active gastric or duodenal ulcer.
    • hemorrhagic cerebrovascular accident (except if there are systemic emboli).
    • severe uncontrolled hypertension.
    • diabetic or hemorrhagic retinopathy.
    • other conditions or diseases involving an increased risk of hemorrhage.
    • injuries to and operations on the brain, spinal cord, eyes, and ears.

Furthermore, spinal/epidural anesthesia is contraindicated where repeated treatment doses of enoxaparin sodium (1 mg/kg every 12 hours or 1.5 mg/kg once daily) are required, due to an increased risk of bleeding.

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 Elonox/Elonox HP 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 Elonox/Elonox HP approved?

Based on Health Canada's review, the benefit–risk profile of Elonox/Elonox HP (hereafter referred to as Elonox) is considered to be similar to that of the reference biologic drug, Lovenox/Lovenox HP (hereafter referred to as Lovenox). Therefore, the benefit–risk profile of Elonox is favourable for the prevention of venous thromboembolic disease, treatment of deep vein thrombosis, treatment of unstable angina and non-Q-wave myocardial infarction concurrently with acetylsalicylic acid, and treatment of acute ST-segment elevation myocardial infarction. Similarity between Elonox and Lovenox was established in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.

Elonox (enoxaparin sodium) is the sodium salt of enoxaparin, a mixture of low molecular weight fragments of heparin sodium, obtained by alkaline depolymerization of the benzyl ester of heparin sodium. The heparin sodium is obtained from porcine intestinal mucosa. Enoxaparin has antithrombotic properties. It preferentially potentiates the inhibition of coagulation factors Xa and IIa and only slightly affects other hemostatic mechanisms such as clotting time. The antithrombotic effect of enoxaparin is well correlated to the inhibition of coagulation factor Xa.

Based on an extensive analytical and biological similarity assessment of Elonox, in conjunction with comparative non–clinical data and comparative clinical pharmacodynamic data, the sponsor sought authorization for each of the indications held by the Canadian reference biologic drug, Lovenox.

Following review of the submitted data, the biosimilar and the reference biologic drug were judged highly similar in terms of quality attributes as assessed in the comparative structural and functional studies. A single–dose comparative pharmacodynamic study demonstrated pharmacodynamic similarity between Elonox and the reference biologic drug in healthy adult male subjects.

The safety profile of Elonox (including the risk of bleeding–related adverse events) is considered to be comparable to that which has been established for the reference biologic drug, Lovenox. The Adverse Reactions section of the Elonox/Elonox HP Product Monograph is based on the clinical experience with the reference biologic drug. Adverse reactions reported during the post-marketing use of enoxaparin sodium (including heparin-induced thrombocytopenia, a severe immune-mediated thrombocytopenia) are also listed. Appropriate warnings and precautions are in place in the Elonox/Elonox HP Product Monograph to address the identified safety concerns.

A Risk Management Plan (RMP) for Elonox was submitted by Fresenius Kabi Canada Ltd. to Health Canada. 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. Upon review, the RMP was considered to be acceptable.

The submitted inner and outer labels, package insert, and Patient Medication Information section of the Elonox/Elonox HP 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 Elonox/Elonox HP was accepted.

Based on an assessment of the relevant information provided in the submission, Elonox is considered to have a benefit–risk profile similar to that established for the claimed indications, which are currently held by the reference product, Lovenox. Therefore, the benefit-risk balance for Elonox is considered favourable for the same indications, doses, and routes of administration authorized for Lovenox.

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 Elonox/Elonox HP?

Submission Milestones: Elonox/Elonox HP

Submission MilestoneDate
Pre-submission meeting2020-11-20
New Drug Submission filed2021-10-21
Screening
Screening Acceptance Letter issued2021-12-09
Review
Request granted to pause review clock for 14 days (extension to respond to clarification request)2022-02-08
Request granted to pause review clock for 9 days (extension to respond to clarification request)2022-02-23
Review of Risk Management Plan completed2022-06-29
Non-clinical evaluation completed2022-10-12
Clinical/medical evaluation completed2022-10-12
Quality evaluation completed2022-10-19
Labelling review completed2022-10-25
Notice of Compliance issued by Director General, Biologic and Radiopharmaceutical Drugs Directorate2022-10-26

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

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 Elonox/Elonox HP 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 Elonox/Elonox HP 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.

5 What post-authorization activity has taken place for Elonox/Elonox HP?

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 decisions were negative or positive. The PAAT will continue to be updated during the product life cycle.

At this time, no PAAT is available for Elonox/Elonox HP. When available, the PAAT will be incorporated into this SBD.

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:

7 What was the scientific rationale for Health Canada's decision?
7.1 Quality Basis for Decision

Elonox/Elonox HP (hereafter referred to as Elonox) was developed as a biosimilar to the reference biologic drug, Lovenox/Lovenox HP (hereafter referred to as Lovenox). 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

The biological activity of Elonox is considered to be representative of the mechanism of action and pharmacological effect of Lovenox. The reference product Lovenox was therefore a suitable proxy for Elonox as it met all the requirements set forth in the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.

Based on findings from several analytical studies, Elonox was found to be highly similar to Lovenox with respect to its structure, physicochemical properties, biological activities, stability, and impurities.

Characterization of the Drug Substance

Enoxaparin sodium is the sodium salt of a low molecular mass heparin that is obtained by alkaline depolymerization of the benzyl ester derivative of heparin from porcine intestinal mucosa. Enoxaparin consists of a complex set of oligosaccharides that have not yet been completely characterized. Based on current knowledge, the majority of the components have a 4–enopyranose uronate structure at the non–reducing end of their chain. Approximately 15% to 25% of the components have a 1,6–anhydro structure at the reducing end of their chain.

Results from process validation studies indicate that the processing steps adequately control the levels of product– and process–related impurities.

Manufacturing Process of the Drug Substance and Drug Product and Process Controls

The starting material for the drug substance manufacturing process is heparin sodium, which is prepared from crude heparin derived from pooled porcine intestinal mucosa. Following salification and esterification steps, the resulting heparin benzyl ester undergoes depolymerization by alkaline hydrolysis to yield crude enoxaparin sodium. Subsequently, the crude enoxaparin sodium is purified and lyophilized to obtain the final drug substance.

The drug product manufacturing process involves weighing the drug substance, compounding and first filtration of the bulk solution, sterile filtration, aseptic filling into syringes and stoppering, visual inspection, and secondary packaging.

Sufficient data were provided from the process validation studies to demonstrate that the manufacturing processes are consistent, reproducible, and generate a drug substance and a drug product that are uniform in quality and in compliance with a defined quality profile.

None of the non-medicinal ingredients (excipients) found in the drug product are prohibited by the Food and Drug Regulations. The compatibility of enoxaparin sodium with the excipients is supported by the stability data provided.

Control of the Drug Substance and Drug Product

The release specifications for the drug substance are supported by sufficient data and the test methods used are either compendial or validated. Batch analysis data met specifications and were consistent among the process validation lots.

Elonox and Elonox HP are Schedule D (biologic) drugs and are, therefore, subject to Health Canada’s Lot Release Program as per Health Canada’s Guidance for Sponsors: Lot Release Program for Schedule D (Biologic) Drugs. The consistency test results support the suitability of the selected methods for their intended purpose and the consistency of the manufacturing process. For post-approval monitoring, Elonox and Elonox HP have been assigned to Lot Release Evaluation Group 3, as they are considered to require a moderate level of assessment. Before each lot is sold, a formal Release Letter from Health Canada is required to approve the sale of the lot in Canada. This assessment level also involves the review of testing protocols, and samples may be requested periodically. The risk level associated with a drug product is determined by factors including the nature of the product, its indication and target patient population, and the manufacturer's production and inspection history.

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 proposed 36–month shelf life at 15 °C to 25 °C for Elonox and Elonox HP are considered acceptable.

Facilities and Equipment

An on–site evaluation (OSE) was not recommended for the site at which heparin sodium (the starting material for the manufacture of the drug substance, enoxaparin sodium) is prepared due to the significant depth of experience at this site in the manufacture of heparin sodium of compendial grade.

The risk assessment score for the drug substance and drug product manufacturing site was sufficient to warrant an OSE. However, an OSE could not be conducted due to the coronavirus disease 2019 (COVID–19) pandemic and the fact that the product was not in production during the review period. The inability to conduct an OSE was adequately mitigated by a thorough review of additional documentation related to facilities and equipment.

Adventitious Agents Safety Evaluation

The drug substance and drug product manufacturing processes incorporate adequate control measures to prevent contamination and maintain microbial control. Purification process steps designed to remove and inactivate viruses are adequately validated.

The biologic raw materials used during manufacturing originate from sources with no or minimal risk of transmissible spongiform encephalopathy (TSE) or other human pathogens.

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.

Comparative in vitro pharmacodynamic and in vivo toxicology studies were conducted for Elonox/Elonox HP (hereafter referred to as Elonox) with the reference product, Clexane (authorized in the European Union).

The comparative toxicological study indirectly evaluated the immunogenic comparability of Elonox with other enoxaparin sodium products when administered as complexes with human platelet factor 4 (hPF4) in a Good Laboratory Practices (GLP)–compliant in vivo study in mice. Of the 69 mice utilized in the study, there were no treatment-related deaths or toxicities. Samples positive for anti-drug antibodies were observed in mice for Elonox, Lovenox and Clexane, and are comparable between each group. Clexane is the same enoxaparin sodium product as Lovenox, and both are produced by the same manufacturer. Clexane was considered a suitable proxy for the reference product Lovenox as it met all of the requirements set forth in the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document. Based on the available data at the time of review, the immunogenicity potential of Elonox is not expected to differ from that of the reference products to a clinically meaningful extent.

The results of the comparative non-clinical studies as well as the potential risks to humans have been included in the Elonox/Elonox HP Product Monograph. Considering the intended use of Elonox/Elonox HP, there are no pharmacological or toxicological issues within this submission which preclude authorization of the product.

For more information, refer to the Elonox/Elonox HP 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

The mechanism of action of enoxaparin sodium (the medicinal ingredient in Elonox/Elonox HP) is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. Enoxaparin sodium preferentially potentiates the inhibition of coagulation factors Xa and IIa, and only slightly affects other hemostatic mechanisms such as clotting time. The antithrombotic effect of enoxaparin sodium is well correlated to the inhibition of factor Xa.

A comparative pharmacodynamic study (Study 0356–18) was conducted in healthy adult male subjects to support the overall assessment of biosimilarity from the clinical perspective. The study was to establish comparability in the pharmacodynamic parameters between Elonox and the reference biologic drug Clexane (enoxaparin sodium solution, 100 mg/mL, authorized in the European Union). Clexane is the same enoxaparin sodium product as Lovenox, and both are produced by the same manufacturer. Clexane was considered a suitable proxy for the reference biologic drug Lovenox marketed in Canada as it met all of the requirements set forth in the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document.

No Phase III clinical efficacy and safety studies were submitted.

Study 0356–18 was designed to assess pharmacodynamic endpoints of Elonox (enoxaparin sodium solution, 100 mg/mL) versus Clexane (enoxaparin sodium solution, 100 mg/mL) administered subcutaneously as a single–dose of 100 mg in healthy adult male subjects. The study evaluated 40 healthy subjects, with 20 subjects randomized to each treatment sequence: either Elonox/Clexane or Clexane/Elonox. One subject did not complete the study, which resulted in 39 subjects being included in the statistical comparisons.

The point estimate for the geometric least squares mean ratio for maximum anti–Xa activity (anti–Xamax) was 106.5%. The 95% confidence interval (CI) for the geometric least squares mean ratio for the area under effect in plasma versus time curve from time zero to the last measurable effect (AUEC0-t) of anti–Xa was 107.9% to 115.3%. These results were within the equivalence margins of 80.0% to 125.0%, thereby demonstrating the comparability between Elonox and Clexane for anti–Xa activities.

The comparative pharmacodynamic criteria with respect to maximum anti–IIa activity (anti–IIamax) and AUEC0-t for anti–IIa were also met. The ratio of anti–Xa to anti–IIa and the measurements of baseline-uncorrected and baseline-corrected tissue factor pathway inhibitor between the biosimilar and reference biologic drug are also supportive of comparable pharmacodynamics between Elonox and Clexane.

Data from this study demonstrated that the biosimilar and reference biologic drug were well tolerated. There were no deaths, or serious or significant adverse events. One non-serious adverse event was reported by one subject during the conduct of the study. There were no clinically significant findings in the vital signs assessment, electrocardiogram recordings, and laboratory tests in any of the subjects in the study.

Overall, the findings from the comparative bioavailability study indicate that there are no clinically meaningful differences between the biosimilar and the reference biologic drug.

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

Indications

Similarity between Elonox/Elonox HP and the reference biologic drugs, Lovenox/Lovenox HP, was established in accordance with the Information and Submission Requirements for Biosimilar Biologic Drugs Guidance Document. 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 and therefore clinical studies are not required to support each indication.

Within this drug submission, the sponsor provided an acceptable scientific justification for requesting the authorization of each of the indications currently granted to the reference products, Lovenox and Lovenox HP.

Based on the evidence submitted, Elonox/Elonox HP were authorized for the same indications currently held by Lovenox/Lovenox HP, as follows:

  • The prophylaxis of thromboembolic disorders (deep vein thrombosis) in patients undergoing:
    • orthopedic surgery of the hip or knee. In addition, Elonox is indicated in hospital or after hospital discharge for long-term prevention of venous thromboembolic diseases following hip replacement surgery.
    • high risk abdominal, gynecological, or urological surgeries.
    • colorectal surgery.
  • The prophylaxis of deep vein thrombosis in medical patients who are at moderate risk of deep vein thrombosis and who are bedridden due to moderate to severe acute cardiac insufficiency (New York Heart Association [NYHA] class III or IV heart failure), acute respiratory failure revealing or complicating chronic respiratory insufficiency not requiring ventilatory support and acute respiratory infections (excluding septic shock), who require short-term prophylaxis of deep vein thrombosis.
  • The prevention of thrombus formation in the extracorporeal circulation during hemodialysis.
  • The treatment of deep vein thrombosis, with or without pulmonary embolism.
  • The treatment of unstable angina or non–Q–wave myocardial infarction, concurrently with acetylsalicylic acid.
  • The treatment of acute ST–segment elevation myocardial infarction, including patients to be managed medically or with subsequent percutaneous coronary intervention.

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