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.

Entresto generated sales of $6bn in 2023 for Novartis, making it the company’s top-selling product. Image credit: Shutterstock / Taljat David. Novartis ’s bid to block the launch of a biosimilar for its best-selling drug Entresto (sacubitril/valsartan) got off to a faltering start, as the drugmaker failed to convince a US court that MSN Pharmaceuticals’ (MSNPI) copycat infringed on a patent. Richard Andrews, district judge for the District of Delaware, ruled the likelihood that Novartis would win the lawsuit was not high enough, meaning a preliminary injunction was not granted. While Andrews stated that stopping MSNPI’s generic launch was not justified, he did order a temporary 72-hour halt while Novartis goes to the US Court of Appeal to seek an injunction, as per a 12 August court document first released by Reuters. The hearing is part of a lawsuit initiated by Novartis to fend off MSNPI’s generic – which received US Food and Drug Administration (FDA) approval last month – to protect sales for its heart failure blockbuster. Novartis’s reference drug was greenlit by the FDA just under a decade ago and has become the company’s top-selling product. It generated sales of $6bn in 2023, with Novartis predicting strong sales for 2024 based on the assumption that no generics would enter the market this year. An analysis by GlobalData’s Pharma Intelligence Center predicted that Entresto sales will peak in 2025, after which it will drop due to generic competition. GlobalData is the parent company of Pharmaceutical Technology. See Also: Madrigal plans to solidify Rezdiffra’s position in MASH despite start being slower than expected Pfizer touts positive topline data for RSV vaccine Abrysvo In an email to Pharmaceutical Technology, a Novartis spokesperson said : “[We] are considering all available options to vigorously defend our intellectual property rights. Novartis added that “any launch at this time would be at risk of later litigation developments”. MSNPI did not immediately respond to a request for comment. The most recent case centred around the use of the drug’s active compound called ‘TVS’, comprising sacubitril, valsartan, and sodium cations. TVS is present in an amorphous solid form in Entresto, which is protected by a patent until November 2026. Novartis sued MSNPI and others seeking to launch Entresto generics in 2022 for infringing on this patent. Novartis argued that MSNPI’s asset uses solid forms of TVS, not the crystalline complex that MSNPI claims. MSNPI argued back, successfully, that spectra analysis of its candidate showed no evidence of amorphous TVS. Andrews also rejected Novartis’s contention that it would experience ‘irreparable harm’ in the absence of an injunction. The drugmaker had stated that MSNPI’s launch could trigger at-risk launches by several other generic drugmakers, thereby “destroying Entresto’s market momentum and causing Novartis to suffer immediate irreparable harm in the form of lost sales, lost market share, loss of formulary position, and price erosion”. During the proceedings, Novartis highlighted MSNPI’s financial stature, suggesting that it would not be able to cover monetary damages in the event of losing the lawsuit. Judge Andrews rebuffed: “I am confident that MSNPI, a large generic drugmaker with prior experience in conducting at-risk launches would be sufficiently prepared to launch its generic sacubitril/valsartan products without being driven to financial ruin by possible litigation losses.” The Delaware court also shunned a motion in July 2023 brought by Novartis, which centred around a patent protecting the combination of sacubitril with valsartan – it too will go to the US Court of Appeals. Novartis has separately filed a lawsuit with a federal court in Washington, D.C., claiming the FDA’s approval of a generic version of Entresto is unlawful. Novartis stated it is maintaining its financial guidance for 2024, as well as its mid-term guidance of +5% sales CAGR for 2023-2028. Novartis is not the only pharma company fighting competition through court cases. Regeneron and Bayer have been locked in patent infringement lawsuits as the companies protect their $6bn revenue-generating biologic Eylea (aflibercept). Roche meanwhile has been fighting India-based Zydus Lifesciences from selling a copycat version of its breast cancer drug Perjeta (pertuzumab).