Why are generic firms rechallenging Precedex's patent?

Ilsung IS files invalidation trial against Precedex formulation patent

Eight generics already on the market… patent was circumvented in 2020

Companies seek to invalidate the ‘glass vial and premix formulation’ portion of the patent

An invalidation trial has been filed against the premix formulation patent of Pfizer’s sedative ‘Precedex (dexmedetomidine).’ What is interesting is that generic drug manufacturers had already succeeded in circumventing this patent back in 2020. In this context, some interpret this move as the generic companies’ attempt to launch a premix formulation and glass vial product containing the same active ingredient.

According to industry sources on the 1st, Ilsung IS recently filed an invalidation trial against Hospira regarding the Precedex premix formulation patent.

Precedex, approved in June 2010, is used for ‘sedation of patients who are intubated early under intensive care and receiving mechanical ventilation.’ Pfizer acquired the product through its acquisition of Hospira in 2015. Subsequently, Pfizer Korea received additional approval for the premix formulation in 2017.

There are two patents related to Precedex. The substance patent expired in January 2013, leaving the formulation patent, which is set to expire in June 2032, as the current target of generic challenges.

Generics were launched sequentially following the expiration of the substance patent. Companies including Ilsung IS, Hanlim Pharm, Penmix, Kyongbo Pharmaceutical, Pharmbio Korea, Hana Pharm, and Jeil Pharmaceutical obtained approvals. However, due to the active premix formulation patent, products were released in ampoule form, requiring mixing the dexmedetomidine-containing drug into a basic intravenous solution.

In 2020, JW Life Science and Dai Han Pharm attempted to circumvent the premix formulation patent. JW argued that its proprietary container did not fall within the patent scope of Pfizer’s Precedex and won both first and second trials. It subsequently launched premix generics with its partners Hanlim and Hana Pharm. However, these products used special plastic infusion containers rather than the original glass vial.

What is notable this time is that Ilsung IS chose to file an invalidation trial rather than a circumvention trial, as JW had filed. Given that circumvention trials generally have higher chances of success at first instance, Ilsung appears to have chosen a more difficult path.

This is interpreted as an attempt to secure not only the premix formulation but also the glass vial packaging format.

The premix formulation patent describes a ‘ready-to-use liquid pharmaceutical composition containing dexmedetomidine or its pharmaceutically acceptable salt thereof, placed in a sealed glass container for parenteral administration.’ Since the patent explicitly specifies a “sealed glass container,” its circumvention allows the sale of premix formulations but not in glass vials, as doing so would risk patent infringement.

Glass vials and plastic infusion bags each have clear advantages and disadvantages. Plastic IV bags have the advantage of a relatively lower risk of breakage. Their light weight, which facilitates transportation, is also cited as an advantage. However, compared to glass vials, there is a greater risk of drug molecule leaching or adsorption. Additionally, reduced stability during long-term storage is pointed out as a drawback.

On the other hand, glass vials prevent the drug from reacting with the packaging material, allowing it to maintain its purity for a long time. They also remain stable during long-term distribution and storage. This is why glass vials are the standard for pharmaceuticals that require long-term stability, despite the higher risk of breakage.

The domestic market size for dexmedetomidine-based sedatives is estimated at around KRW 19 billion annually. According to the Ministry of Food and Drug Safety, domestic production and import volumes increased from KRW 16 billion in 2022 to KRW 19 billion in 2023, but declined back to KRW 16 billion in 2024 due to reduced usage amid the healthcare crisis. Pfizer’s two products account for about 40% of the total supply as of 2024.