1.) FDA First Generics Breakdown 2.) EPO Revokes Nubeqa: Darolutamide Generic Launch in Europe: How EPO Revocation of EP 3 250 554 Opens a 10-Month Commercial Window

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API & IP Intelligence Roundup (28 September 2026)

This edition evaluates the commercial dynamics of the FDA's 91 "First Generic" approvals, key corporate legal developments including Novartis's dismissal of purchaser antitrust litigation on Entresto, Lantheus's radiopharmaceutical nod, and an EPO Board of Appeal decision revoking Orion Corporation’s darolutamide polymorph patent, unlocking a valuable generic window in Europe.

1. FDA First Generic Drug Approvals: Commodity Cliffs vs. High-Barrier Niches

The FDA CDER list highlights 91 inaugural generic clearances, illustrating two distinct market dynamics:

• Rapid Generic Erosion in Small Molecules: Highly contested patent cliffs saw immediate crowding from multiple sponsors. The primary example is Rivaroxaban tablets (2.5 mg), where over 10 global and Indian generic filers (including Lupin, Dr. Reddy's, Alembic, Biocon, Macleods, and Alkem) gained approvals against the $4B+ US franchise, triggering rapid price competition. Similarly, Sitagliptin/Metformin (Januvia/Janumet) faced immediate multi-source erosion from Watson, Sandoz, and PH Health.

• High Margin Preservation in Complex Delivery Systems: Generic developers with advanced formulation capabilities captured high-margin spaces with limited competition. Notable entries include Amneal’s Qvar (beclomethasone inhaler), Teva’s Saxenda (liraglutide GLP-1 injection), Sandoz/Mylan's Venofer (complex iron sucrose injection), and Aveva's ZTlido (lidocaine patch 1.8%).

2. Global Corporate & Regulatory Updates

• Novartis Wins Entresto Orange Book Antitrust Suit: U.S. District Judge Lewis Liman dismissed a proposed class action by purchaser funds accusing Novartis of anticompetitive Orange Book patent listing to delay generic competition for its blockbuster heart failure drug.

• Lantheus Obtains FDA Approval for Bravnetsa: The FDA granted final approval for Bravnetsa (ANDA 217060), a generic radiopharmaceutical equivalent to Lutathera® for gastroenteropancreatic neuroendocrine tumours, strengthening Lantheus ahead of a shareholder vote on Curium's acquisition.

3. European IP Benchmark: EPO Revokes Nubeqa (Darolutamide) Polymorph Patent

In Case T 0889/24, the EPO Technical Board of Appeal set aside the Opposition Division’s decision and revoked Orion Corporation’s EP 3 250 554 covering stable crystalline Form I' and Form I'' diastereoisomers of darolutamide:

• The "Inevitable Result" Doctrine (Article 56 EPC): Because the diastereoisomers rapidly interconvert in vivo, the Board deemed stereoisomer separation a routine alternative. Relying on experimental data (D10), the Board held that subjecting solid darolutamide to standard thermal screening (DSC/TGA) inevitably leads to Form 1 as the most thermodynamically stable phase, defeating inventive step.

• 10-Month European Generic Launch Window: Darolutamide European sales exceeded €300M in 2024/2025. EP 3 250 554 was slated to expire in January 2036. With basic compound Supplementary Protection Certificates (SPCs) expiring in late March 2035 across major European jurisdictions (DE, FR, IT, ES, UK), the patent's revocation creates an approximately 10-month unencumbered commercial launch window for generic manufacturers prior to 2036.

#PharmaIP #FDA #GenericDrugs #FirstGenerics #Darolutamide #Nubeqa #PatentLaw #EPO #Entresto #RegulatoryAffairs #SidvimBlog

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Contents

2025 First Generic Drug Approvals

General information

Novartis defeats drug-purchaser lawsuit over delay of Entresto generics

Lantheus Holdings wins FDA approval for Bravnetsa before Curium vote

Intellectual Property

Darolutamide: An early launch opportunity in Europe?

2025 First Generic Drug Approvals

Each year, FDA’s Centre for Drug Evaluation and Research (CDER) approves a wide range of new drug products. FDA provides the scientific and regulatory advice needed to bring safe, effective, high-quality generic alternatives to market, which in turn creates more affordable treatment options for patients. The FDA updated the list on its website in May 2026. 

“First generics” are exactly what they sound like: the first FDA approval that allows a manufacturer to market a generic drug product in the United States. The FDA considers first generics important to public health and prioritises their review.

There are about 91 first generic approvals. The most visible example is rivaroxaban tablets, where intense multi-sponsor competition materialised almost instantly after the patent cliff, with nearly a dozen Indian, North American, and global players securing simultaneous or staggered approvals to capture shares of multi-billion-dollar brand franchises. Conversely, high-barrier delivery forms such as beclomethasone metered-dose inhalers, complex iron sucrose parenteral, and specialised topical lotions preserved pricing margins for developers with advanced formulation and regulatory capabilities. 

The table below summarises key approvals. 

General information

Novartis defeats drug-purchaser lawsuit over delay of Entresto generics

A federal judge in Manhattan ruled for Novartis on Wednesday against allegations that it misused one of its patents to maintain its exclusivity on its blockbuster heart-failure drug Entresto.

US District Judge Lewis Liman dismissed a lawsuit filed on behalf of drug purchasers who argued that Novartis improperly characterised the patent as covering Entresto in order to delay generics of the drug.

The New York-based Iron Workers Local 580 Insurance Fund filed the proposed class action lawsuit last ⁠year on behalf of Entresto buyers. It argued that purchasers paid inflated prices for the drug after Novartis improperly listed one of its patents in the US Food and Drug Administration's Orange Book – which lists patents covering drugs that the FDA has deemed safe and effective – to prevent generics from entering the market.

News here

Lantheus Holdings wins FDA approval for Bravnetsa before Curium vote

The U.S. list of approved treatments for adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours grew on Tuesday after Lantheus Holdings, Inc. said the FDA granted final approval to Bravnetsa, a radiopharmaceutical equivalent to Lutathera. The decision moves abbreviated application 217060 beyond tentative approval, giving Lantheus an approved adult cancer therapy as it prepares for a vote on its sale to privately held Curium. 

News here

Intellectual Property 

Darolutamide: An early launch opportunity in Europe? 

Case Overview & Procedural History

On 23 June 2026, the Technical Board of Appeal of the European Patent Office (EPO) issued its decision in Case T 0889/24. Opponent Hamm & Wittkopp Patentanwälte PartmbB appealed the Opposition Division's decision of 7 May 2024, which rejected the opposition and maintained European Patent No. 3 250 554 in granted form. The patent proprietor is Orion Corporation.

The patent relates to solid crystalline forms of the diastereoisomers of the active ingredient darolutamide (N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide) and methods of preparing them. Darolutamide (marketed as Nubeqa by Bayer and Orion) is a potent androgen receptor (AR) antagonist approved for prostate cancer.

The Board of Appeal set aside the Opposition Division’s decision and revoked the patent in its entirety for lack of inventive step under Article 56 and Article 100(a) EPC.

The Patented Claims at Issue

Independent claims 1 and 3 of the main request (granted claims) defined specific crystalline polymorphs of the separated diastereoisomers:

• Claim 1: Crystalline Form I' of diastereoisomer (Ia) (the (S,S)-configuration) having an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.3, 15.7, 17.0, 24.1, and 25.1 ± 0.15° 2-theta.
• Claim 3: Crystalline Form I'' of diastereoisomer (Ib) (the (S,R)-configuration) having an XRPD pattern comprising peaks at 9.2, 10.9, 15.1, 15.8, and 22.1 ± 0.15° 2-theta.

Key Legal & Technical Findings

1. Closest Prior Art Starting Point

The Board rejected Orion’s contention that the assessment should start from prior art document D1 (WO 2011/051540 A1) as a whole rather than a specific example (citing T 1126/19 and T 2759/17). While D1 disclosed over 300 examples, Table 1 explicitly singled out 19 compounds with biological activity data, including Example 56 (darolutamide as a solid diastereomeric mixture). Under T 2759/17, a skilled person realistically starts from compounds highlighted with activity data for the intended therapeutic objective. Thus, Example 56 was deemed a non-arbitrary starting point.

2. Distinguishing Features & Objective Technical Problem

The parties agreed on two distinguishing features over Example 56 of D1:

1. The separation of the individual diastereoisomers (Ia and Ib).
2. The provision of the separated diastereoisomers in specific crystalline forms (Form I' and Form I'').

Because the two diastereomers rapidly interconvert in vivo, they possess identical biological activity. Diastereomer separation thus solved merely the problem of providing an alternative, a routine task for the skilled person.

For the crystalline forms, Orion asserted that Forms I' and I'' exhibited superior thermodynamic and polymorphic stability, were unsolvated, and showed no weight loss below their melting points. The Board framed the objective technical problem as providing a form of darolutamide stable over a broad temperature range and exhibiting thermodynamic and polymorphic stability.

3. Obviousness: Inevitable Outcome of Routine Characterisation

The Board held that the claimed crystalline forms were obvious over Example 56 of D1:

• Routine Characterisation: Investigating a solid drug candidate involves routine solid-state characterisation using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
• Thermal Behaviour (Post-Published Data D10): Examination document D10 showed that heating any of the 15 investigated crystalline forms of darolutamide beyond their transition temperatures converted them to Form 1 (Forms I' and I''). Form 1 was the most stable form across a broad temperature range.
• Use of Post-Published Evidence: The Board clarified that D10 was not used as prior art establishing expectations, but as post-published factual evidence demonstrating the inevitable result of heating during routine testing.
• Rejection of Speculative Hypotheses: Orion argued that heating might generate amorphous phases (citing D16) or enantiotropic systems. The Board rejected this, holding that specific experimental data on the actual drug molecule outweighed general literature hypotheses.

Strategic & Industry Implications

Decision T 0889/24 establishes a rigorous benchmark for polymorph patentability before the EPO:

• The "Inevitable Result" Doctrine: Identifying the thermodynamically most stable polymorph through standard heating or thermal screening lacks inventive step if routine analytical techniques (DSC/TGA) inevitably yield that form.
• Impact on Nubeqa Generics: Total revocation of EP 3 250 554 removes a major European polymorph patent shielding darolutamide, clearing the patent runway for generic competitors targeting the commercial landscape. This decision could offer an early launch opportunity for generics. The EP 3 250 554 patent would have expired in January 2036. This could be a good product for a generic company in EU markets. According to one news article, European sales reached €180–220 million in 2023 and expanded to an estimated €300 million+ across Europe in 2024/2025 as reimbursement and market access for the mHSPC indication scaled across Germany, France, Italy, the UK, and Spain.
• The compound is claimed in EP 2 493 858. SPCs based on EP 2 493 858 have been filed and granted across major national patent offices in Europe (e.g., DE, FR, IT, ES, GB, NL, etc.), extending compound exclusivity for darolutamide in those jurisdictions through late March 2035. Thus, in Europe, generic companies may have about a 10-month window to launch early.  

Decision here