Entresto patent dispute near its end, yet 0 generic approval

Generic companies win successive disputes since 2021…two rulings in the Supreme Court remain

10 companies have applied for marketing authorization, yet there are '0 approvals'

MFDS is requesting supplementary documentation…'cocrystal' generic approval remains the key determinant

Product photo of Entresto

The patent dispute of Novartis' heart failure treatment, 'Entresto,' is nearing its final judgment.

 

Still, generic companies may be unable to launch their products early, regardless of the ruling.

 

To launch a generic early, companies need not only to win the patent dispute but also to secure product approval from the Ministry of Food and Drug Safety (MFDS).

 

The MFDS is reportedly demanding supplementary data from the relevant generic companies.

 

In other words, generic manufacturers, after fighting patent battles for five years, risk winning the legal fight only to be unable to launch their product.

 

Not a simple combination drug but a 'cocrystal complex'...may be delaying generic approval According to the MFDS on October 13, there are currently zero product approvals for Entresto generics.

 

This is considered unusual given that generic product approvals are typically processed within a year and a half of application.

 

Approximately 10 generic companies involved in the Entresto patent dispute applied for generic product approval sequentially from April 2022 to July of the following year.

 

They filed these applications based on their first-instance victory in the patent dispute.

 

However, there has been no news of Entresto's generic product approval for almost 3 years.

 

It is reported that the MFDS is requesting supplementary approval documentation.

 

The pharmaceutical industry is paying attention to the MFDS's request for supplementation regarding Entresto's unique crystal structure.

 

Entresto is a heart failure treatment in which the active ingredients, sacubitril and valsartan, act on cardiac neurohormones through separate pathways.

 

The unique feature is that the two ingredients form a single crystalline structure, a cocrystal complex.

 

Medicines combining two or more ingredients typically involve a simple mixture of the crystalline forms of each component.

 

In contrast, a cocrystal involves two or more components bound together at the molecular level like a single compound.

 

They exhibit single-compound properties until just before absorption into the body.

 

For this reason, the industry refers to Entresto not merely as a 'combination drug' but as a 'complex' with a singular characteristic.

 

The problem is the scarcity of approved generics for this cocrystal formulation.

 

Entresto is reportedly the only drug approved as an API-API cocrystal complex, not only in Korea but also in the U.S.

 

and Europe.

 

Furthermore, there is no precedent anywhere in the world for the approval of a generic for a cocrystal complex drug.

 

The MFDS is contemplating this issue.

 

The Ministry is struggling to find an appropriate analytical method for generic approval.

 

Critics suggest that because the cocrystal structure differs from traditional combination products in its physicochemical properties, applying the same analytical methods may not be suitable for generic approval.

 

A pharmaceutical industry official said, "If it were a typical combination product's crystal form, there would have been no issue with approval, but I understand the MFDS is deeply concerned about whether it is appropriate to use existing methods to analyze this special cocrystal structure and grant generic approval." Winning in the Supreme Court, yet generic companies may face a failed launch Given the circumstances, companies preparing Entresto generics are now in a position where they may be unable to launch their products even if they win the final patent dispute.

 

Generic companies initiated a declaratory judgment action against Novartis's Entresto crystal form patent in January 2021.

 

This was followed by the filing of invalidation and circumvention trials against the use patent, salt/hydrate patent, and formulation patent.

 

Generic companies won successive victories in the first and second instances.

 

Disagreeing with these rulings, Novartis appealed the cases to the Supreme Court.

 

Of the two cases appealed to the Supreme Court, the ruling in the use patent case was finalized in April of last year, with Novartis losing.

 

The remaining pending case is the dispute over the crystal form patent.

 

The full merits review is currently underway, following the dismissal without deliberation deadline in April of this year.

 

Separately, the salt/hydrate patent dispute is awaiting a ruling from the Patent Court.

 

The pharmaceutical industry reportedly anticipates that the final ruling regarding the crystal form patent could be issued as early as this year.

 

If the Supreme Court sides with the generic companies, as in the first and second instances, the generic companies' patent risk would be effectively eliminated.

 

However, regardless of the Supreme Court's decision, if MFDS approval continues to be delayed, generic companies will face a dual burden: winning a five-year-long dispute only to be unable to launch the product.