Apixaban – A potential API for generic drug makers

1. Overview [1]–[3]

Apixaban is a new class of anticoagulant that blocks the clots forming of factor Xa. This new anticoagulant prevents clots from forming by directly blocking both free and clot-bound factor Xa without impacting platelet aggregation, resulting in lower bleeding risk (especially intracranial hemorrhage) compared to Warfarin – a similar-effective anticoagulant.

Apart from apixaban, the group of factor Xa inhibitors also includes some well-known APIs such as rivaroxaban (Xalrelto), edoxaban (Savaysa), fondaparinux (Arixtra), and betrixaban (Bevyxxa).

Currently, apixaban is indicated for the below treatments:

Preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF)
Managing Deep vein thrombosis (DVT) and Pulmonary Embolism.
Preventing venous thrombosis prophylaxis in patients undergoing hip or knee replacement.

2. Evolution of the brandname drug Eliquis^® (apixaban) [3]–[6]

Eliquis^® is the product of co-operation between two pharmaceutical companies, Bristol-Myers Squibb and Pfizer when these two companies officially announced to research and develop the active ingredient apixaban together on April 26, 2007. 4 years later, on May 20, 2011, Eliquis^® was first approved by the European Commission (EC) for use in 27 countries of the European Union (EU), as indicated for the prevention of venous thromboembolism in adults after an elective hip replacement or a knee replacement surgery. Subsequently, on November 20, 2012, the EC further recognized the efficacy of Eliquis® in the prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation. . At the end of 2012, this drug was officially approved by the FDA.

The detailed information of Eliquis^® on ingredients, proportions of ingredients in the formula, and production process which has been compiled in the Library – Brandname drug category on SEN Pharma’s website is here.

3. Revenue and patent of Eliquis^® [3]–[7]

Since its launch, Eliquis^® (apixaban) has always shown strong growth over the years. This new anticoagulant has been widely researched and used for COVID patients who are at high risk of forming clots, resulting in an increase of 16 percent in revenue compared to 2019, reaching 9.17 billion dollars and ranking in the top 5 best-selling drugs in the world in 2020. According to the revenue report in 3 quarters of 2022, Eliquis^® impressively earns 3.2, 3.2, and 1.4 billion dollars.

Large generic drug pharma companies like Milan or Micro Labs have completed registration dossiers for the generic version of apixaban to be ready to compete. However, in August 2017, the US Patent and Trademark Office extended exclusive protection for Eliquis® from February 2023 to November 2026.

4. Patent of brandname drug and API [4], [8]–[11]

Currently, BMS and Pfizer jointly own 3 patents related to apixaban and the Eliquis^® formula, including:

Patent of active ingredient US6413980B1: Nitrogen containing heterobicycles as factor Xa inhibitors (expiration date: 12/22/2019)
Patent of active ingredient US6967208B2 : Lactam-containing compounds and derivatives they as factor Xa inhibitors (expiration date: 21.11.2026)
Patent of the formulation US9326945B2: Apixaban formulations (expiration date: 24.02.2031)

With the aim of adapting the domestic treatment demands right after the exclusive protection of the API patent expired, many generic drug makers in Vietnam started to find the supply sources of apixaban for lab-scale formulation, stability testing, pilot batch production, and registration. It is important that Apixaban particle size should be under 89 um (D90) to meet the standard of the in-vivo bioequivalent test, which is a trend of pharmaceutical research and manufacturing as mentioned in Circular No. 07/2022/TT-BYT.

SEN Pharma is proud to be a partner with Unipharm, a top ingredient supplier in China, which has quality apixaban ingredients with required documents for regulatory affairs at reasonable prices.

Having strong connections with over 100 ingredient manufacturers in China and distributing more than 700 APIs, Unipharm would be a perfect ingredient supplier for pharmaceutical manufacturers in Vietnam.

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