Regulatory Decision Summary for Inclunox, Inclunox HP
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of this new drug submission was to seek market authorization for Inclunox (enoxaparin sodium) as a biosimilar to Lovenox, the reference biologic drug in Canada, on the basis of comparative quality, non-clinical and clinical studies.
The following indications for Inclunox are being sought:
- The prophylaxis of thromboembolic disorders (deep vein thrombosis) in patients undergoing:
- Orthopedic surgery of the hip or knee; in addition, Lovenox 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 (DVT) in medical patients who are at moderate risk of DVT and who are bedridden due to moderate to severe acute cardiac insufficiency (New York Heart Association 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 extra-corporeal 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 (ASA).
- Treatment of acute ST-segment Elevation Myocardial Infarction (STEMI), including patients to be managed medically or with subsequent Percutaneous Coronary Intervention (PCI).
- All these indications are currently authorised for the reference biologic drug in Canada.
A Notice of Compliance (NOC) was recommended and issued.
Why was the decision issued?
Comparable pharmacodynamics (PD) between Inclunox and Lovenox was established in a single dose pivotal comparative PD study in healthy subjects using a European Union (EU)-sourced reference product (known as Clexane) as a suitable proxy for the Canadian reference product. Supportive evidence of comparable PD was also established between Inclunox and a United States-sourced reference product (Lovenox, United States) in a single dose pivotal comparative PD study conducted in healthy subjects.
For the pivotal comparative PD study comparing Inclunox with EU-Clexane, PD comparability (anti-FXa and anti-FII as the relevant PD surrogates of efficacy) was demonstrated as the 95% Confidence Intervals (CIs) for the ratio of geometric means (GMR) of Area under the Concentration Effect Curve (AUEC0-t) and Maximum Activity (Amax) were within the equivalence interval of 80.0% to 125.0%.
For the supportive comparative PD study comparing Inclunox with Lovenox (United States), PD comparability (anti-Xa and anti-IIa as the relevant PD surrogate of efficacy) was also demonstrated as the pre-specified 90% CIs (as well as post-hoc analysis using 95% CIs) for the GMR of AUEC0-t and Amax were within the equivalence interval of 80.0% to 125.0%.
The safety profile of Inclunox was consistent with the known safety profile of Lovenox. The known risks of Lovenox have been included in the Product Monograph (PM) for Inclunox. The Contraindications, Warnings and Precautions, and Adverse Reactions sections of the PM for Lovenox have been retained in the PM for Inclunox.
Similar efficacy and safety of Inclunox as compared to EU-Clexane were derived from the similarity of physicochemical characteristics, biological activity/potency, and the pharmacodynamic (PD) profiles. The demonstrated similarity, along with an acceptable justification based on the mechanism of action of the proposed product formed the basis of the rationale to allow extrapolation to other routes of administration and indications licensed for the reference product, Lovenox.
The final decision for Inclunox was based on the totality of evidence, including comparative analytical and functional, non-clinical and pharmacodynamic (PD) comparisons in healthy volunteers. Therefore, the benefit/risk balance for Inclunox is considered favourable for the indications, doses and routes of administration for which the Canadian reference product, Lovenox, are licensed and are recommended to be granted to Inclunox.
For more information on Health Canadas decision, please view the Summary Basis of Decision.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| INCLUNOX | 02507536 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 60 MG / 0.6 ML |
| INCLUNOX | 02507501 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 30 MG / 0.3 ML |
| INCLUNOX HP | 02507579 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 150 MG / 1 ML |
| INCLUNOX HP | 02507560 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 120 MG / 0.8 ML |
| INCLUNOX | 02507528 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 40 MG / 0.4 ML |
| INCLUNOX | 02507544 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 80 MG / 0.8 ML |
| INCLUNOX | 02507552 | SANDOZ CANADA INCORPORATED | ENOXAPARIN SODIUM 100 MG / 1 ML |