A federal judge in Delaware delivered a significant blow to Novartis on Monday, denying the pharmaceutical giant's attempt to block the launch of the first generic version of its blockbuster heart failure drug Entresto. District Judge Richard Andrews ruled that Novartis failed to meet the burden of proof required for a preliminary injunction against MSN Pharmaceuticals, whose generic sacubitril and valsartan product received FDA approval in July 2024.
Patent Dispute Centers on Amorphous TVS Compound
The legal battle revolves around TVS, an amorphous solid compound found in Entresto that consists of sacubitril, valsartan and sodium cations. Novartis alleged that MSN's generic product contains sufficient amounts of amorphous TVS—which remains patent-protected until November 2026—to constitute infringement of its exclusivity protections.
However, Judge Andrews sided with MSN's defense, which challenged Novartis' allegations by claiming the company used incomplete data to reach its conclusions. "Novartis bears the burden of proof, both on infringement and showing likelihood of success," Andrews wrote in his ruling, noting that the company fell short of "showing it is likely to succeed in proving MSN's ANDA products contain amorphous TVS."
Court Rejects Irreparable Harm Claims
Beyond the patent infringement issues, Andrews also dismissed Novartis' arguments regarding irreparable harm. The pharmaceutical company had contended that allowing MSN's generic to enter the market could encourage other competitors, "thereby destroying Entresto's market momentum" and leading to lost sales, market share, and formulary positioning.
"I am skeptical about Novartis's characterization of many of its potential harms," Andrews wrote. "I do not find it reasonable to attribute harm resulting from the actions taken by other generic drug makers to MSN's decision to launch its own individual product."
Entresto's Market Significance
The stakes in this legal dispute are substantial, given Entresto's position as Novartis' top-performing asset. The drug, which combines the neprilysin inhibitor sacubitril with the angiotensin receptor blocker valsartan to lower vascular resistance and blood pressure, generated over $6 billion in net sales in 2023. In the first six months of 2024 alone, Entresto brought in $3.77 billion in revenue.
First approved in 2015 for heart failure in adults, Entresto works by helping to reduce the workload on the heart through its dual mechanism of action targeting both the renin-angiotensin system and the natriuretic peptide system.
Regulatory Setbacks Mount
Monday's court decision compounds recent regulatory challenges for Novartis. Two weeks prior, the FDA denied the company's citizen petition aimed at preventing the approval and market entry of Entresto generics. Novartis had filed the petition in September 2022, requesting that the regulator not approve any drug application referencing Entresto until after February 16, 2024, when the drug's three-year exclusivity period under the Orange Book expired.
The petition also included additional requests regarding specific Entresto patents, asking the FDA to block applications that would breach these protections until their respective expiration dates in August 2033 and May 2036. However, the FDA rejected these arguments, stating that drug applicants can modify their labeling to avoid violating patent protections.
Legal Proceedings Continue
Despite the setback, Novartis has secured a temporary reprieve. Judge Andrews issued a three-day hold on the case while the company appeals to the U.S. Court of Appeals for the Federal Circuit. Novartis stated it is "considering all available options" to defend its intellectual property while maintaining its financial guidance for 2024.
The company has also filed a separate challenge in Washington, D.C. district court, seeking to block MSN's launch as part of a broader challenge to the FDA's decision to approve the generic. That court has not yet ruled on Novartis' request.
MSN's generic version of Entresto represents a significant milestone as the first U.S. generic competitor to enter this lucrative market segment, potentially setting the stage for additional generic competition in the heart failure treatment space.
