Sacubitril

iStock, TBE Novartis is seeking to prevent the entry of generics for its blockbuster heart failure drug Entresto, its top-selling asset that brought in more than $6 billion in net global sales last year. An appeals court on Wednesday ruled against Novartis in its bid to block the entry of MSN Pharmaceuticals’ generic competitor to the blockbuster heart failure drug Entresto (sacubitril/valsartan), according to Reuters and other outlets. First approved in 2015 , Entresto is an oral drug indicated for the treatment of heart failure in adults. It combines the neprilysin blocker sacubitril with the angiotensin receptor inhibitor valsartan to lower blood pressure and vascular resistance. Since hitting the market, Entresto has become Novartis’ top-selling asset, raking in more than $6 billion in net sales globally last year. In its decision on Wednesday, the U.S. Court of Appeals for the Federal Circuit agreed with a lower court’s verdict that Novartis had not sufficiently proven that it could win a patent suit against MSN. The appellate judges saw “no clear error in the district court’s analysis,” as reported by Reuters . The tussle over Entresto’s market exclusivity began in September 2022 , when Novartis filed a citizen petition with the FDA, asking the regulator not to approve any drug application that referenced the heart failure drug until after Feb. 16, 2024—the date when its three-year exclusivity period under the Orange Book expires. The pharma also asked the FDA to refrain from approving drug applications that referenced two specific Entresto-related patents, which are set to expire on August 22, 2033 and May 9, 2036, respectively. In July 2024, the FDA rejected the petition , calling the first request moot—given that the exclusivity period had already lapsed—while noting that the two patent-specific requests can easily be avoided by tweaking the labelling of generics applicants. “In accordance with our statutory and regulatory authority, we have determined that in this instance, an [abbreviated New Drug Application] may propose labeling for a generic sacubitril and valsartan product that does not seek approval for the purported use protected” by the patents in question, the FDA wrote in its letter. A month later, in August, Judge Richard Andrews of the United States District Court for the District of Delaware blocked Novartis’ bid for a preliminary injunction against MSN. The pharma alleged that MSN had violated patent protection of TVS, a specific compound found in Entresto that is protected until November 2026. MSN shot back and argued that Novartis had provided incomplete information to substantiate its claims. Andrews sided with MSN, noting that Novartis “bears the burden of proof, both on infringement and showing likelihood of success.” Andrews also said that he was “skeptical” of Novartis’ “characterizations of many of its potential harms” if the injunction is not granted. Aside from generic competition, Entresto’s sales are also threatened by the Inflation Reduction Act’s drug price negotiation program. The Centers for Medicare and Medicaid Services in August 2024 revealed the final maximum fair prices for the first 10 drugs in the program, which include Entresto. The prices are set to take effect in 2026. In October 2024, Novartis lost its court case against the IRA.

External view of Novartis’ office in Canada iStock, JHVEPhoto On the heels of the FDA’s denial of its petition, a Delaware district court on Monday handed Novartis another loss in its efforts to keep the market free of Entresto copycats. A federal judge in Delaware on Monday ruled against Novartis , denying the pharma’s attempt to block the entry of a generic competitor to its oral heart failure drug Entresto (sacubitril and valsartan). District Judge Richard Andrews denied Novartis’ bid for preliminary injunction against MSN Pharmaceuticals, arguing that the pharma did not sufficiently prove that MSN had committed patent infringement in its abbreviated new drug application (ANDA). Novartis’ case revolves around TVS, an amorphous solid compound found in Entresto and consists of sacubitril, valsartan and sodium cations. In its legal complaint, the pharma alleged that MSN’s generic product contains a high enough amount of amorphous TVS—which is patent-protected until November 2026—and violates its exclusivity protections. Meanwhile, MSN challenged the allegations by claiming that Novartis used incomplete data to arrive at its conclusions. Andrews sided with MSN in his ruling, noting that the pharma “bears the burden of proof, both on infringement and showing likelihood of success.” Novartis fell short of “showing it is likely to succeed in proving MSN’s ANDA products contain amorphous TVS,” Andrews wrote. The judge also rejected Novartis’ claims of irreparable harm if it is not granted an injunction. “I am skeptical about Novartis’s characterization of many of its potential harms,” Andrews wrote, referring to the pharma’s argument that allowing MSN’s generic product to hit the market could embolden other copycats, “thereby destroying Entresto’s market momentum” leading to lost sales, market shares and formulary positioning. “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,” Andrews wrote. Entresto combines the neprilysin inhibitor sacubitril with the angiotensin receptor blocker valsartan, helping to lower vascular resistance and blood pressure. The drug was first approved in 2015 for heart failure in adults. In 2023, Entresto emerged as Novartis’ top-performing asset with over $6 billion in net sales . In the first six months of 2024, Entresto bagged $3.77 billion . Monday’s legal loss comes after the FDA two weeks ago denied Novartis’ citizen petition to prevent the approval and entry of Entresto generics. The pharma launched the petition in September 2022 asking the regulator not to green light any drug application that referenced Entresto until after Feb. 16, 2024, when the drug’s three-year exclusivity period under the Orange Book expires. Novartis also outlined additional requests regarding specific Entresto patents, asking the FDA to block applications that would otherwise breach these protections until after they expire in Aug. 22, 2033 and May 9, 2036, respectively. In its rebuff, the regulator insisted that drug applicants can tweak their labeling to avoid violating these patent protections. An ANDA “may propose labeling for a generic sacubitril and valsartan product that does not seek approval for the purported use protected” by Novartis’ patents, according to the FDA.