Pharma Intelligence Alert: 2021 USFDA 505(b)(2) Approvals Study, UK Entresto SPC Ruling, & CDMO Sector Momentum
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Executive Summary
In this edition of the API and IP Newsletter, we present findings from our retrospective analysis of all 2021 USFDA 505(b)(2) NDA approvals, tracking value-added reformulation strategies and top sponsors
. In regulatory compliance and industry news, we cover Q1 CDMO financial growth across Gland, Akums, and Kwality, alongside the recent USFDA warning letter issued to Aurobindo Pharma’s Eugia Unit-I facility . In Intellectual Property, we unpack the UK High Court ruling in Accord Healthcare v. Novartis, which upholds the validity of the Entresto® (sacubitril/valsartan) SPC until January 2028, effectively barring near-term generic launches .
Key Highlights & Strategic Takeaways
1. Decoding Value-Added Formulations: Complete 2021 USFDA 505(b)(2) Analysis
Approval Distribution: The 505(b)(2) pathway saw a total of 69 original approvals in CY 2021, characterised by a mid-year peak in June (16 approvals) and strong year-end momentum across October–December (28 combined approvals)
. Leading Corporate Sponsors: Hikma Pharmaceuticals and Tris Pharma led the approvals table (4 original NDAs each), followed by Almatica Pharma (3 NDAs), and 2 approvals each for Accord Healthcare, ViiV Healthcare, AbbVie, Bayer, and Emergent BioDefense
. Strategic Reformulation Models:
Paediatric Line Extensions: AbbVie referenced its adult NDA data for Mavyret (glecaprevir/pibrentasvir) to support approval of oral pellets for children, using targeted bridging PK/safety trials
. Indication Repurposing & Formulation Optimisation: AbbVie/Allergan re-engineered Pilocarpine HCl (an established glaucoma cholinergic agent) into Vuity (1.25% ophthalmic solution) with optimised pH to treat presbyopia.
High-Dose & Dosing Enhancements: Hikma launched Kloxxado (8 mg naloxone nasal spray), and Tris Pharma expanded Dyanavel XR extended-release amphetamine tablet strengths (5 mg to 20 mg)
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2. CDMO Growth & Regulatory Compliance Updates
Indian CDMO Pipeline Momentum: Gland Pharma, Akums Drugs & Pharmaceuticals, and Kwality Pharmaceuticals all posted double-digit quarterly revenue growth for the period ended 30 June 2026, underlining strong global demand for specialized finished dosage and sterile manufacturing
. USFDA Warning Letter for Aurobindo (Eugia Unit-I): The USFDA issued a formal Warning Letter to Eugia Pharma Specialities' formulation facility in Telangana following an inspection conducted in February 2026, creating regulatory headwinds for the site's injectable pipeline
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3. IP Focus: UK High Court Decision in Accord Healthcare v. Novartis (Entresto®)
The Ruling: Mr Justice Meade dismissed all validity attacks brought by Accord against European Patent (UK) No. 1 467 728 B1 and confirmed the validity of SPC/GB16/025 protecting Entresto®
. Plausibility & Obviousness: The Court confirmed that the basic patent satisfied ab initio plausibility by providing qualitative disclosure of animal efficacy
. Obviousness attacks over Ksander and Trippodo failed because the state of the art contained no teaching or motivation to combine an ARB with a NEPi, and NEPis lacked an established "class effect" . SPC Scope (Articles 1(b) & 3): The Court ruled that the "product" under EU/UK SPC law is the active moiety combination (sacubitril and valsartan in the strict sense), not the crystalline co-complex form
. Consequently, the basic patent and Marketing Authorisation validly support the SPC . Commercial Impact on Generic Entry: Commercial launch of all generic sacubitril/valsartan products (including physical admixtures and co-crystals) remains legally barred in the UK until 15 January 2028, shielding Novartis' multi-billion-dollar franchise for an additional 14 months past data exclusivity expiry (23 November 2026)
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Decoding Value-Added Formulations: Complete Analysis of 2021 USFDA 505(b)(2) Approvals
General information
Gland vs Akums vs Kwality: Which Pharma CDMO Has the Strongest Growth Pipeline?
USFDA issues warning letter to Aurobindo Pharma’s Telangana facility; stock dips 2 pc
Intellectual Property
Accord Healthcare Limited v Novartis AG -UK High Court Decision
- Lifecycle Management and Portfolio Trends: Evaluating how drug developers deployed the 505(b)(2) pathway to defend against patent cliffs and enter adjacent markets.
- Submission Types and Formulation Trends: Identifying high-growth areas, from ready-to-use (RTU) injectables to fixed-dose combinations.
- Competitive Landscape: Highlighting the most active sponsors and specialised CDMOs in the 505(b)(2) space.
- Commercial and Pricing Power: Analysing products that secured premium pricing and market exclusivity by addressing critical patient compliance and caregiver burdens.
- We will publish an extensive analysis of all 505(b)(2) approvals in CY 2021 on our website in due course. The Glimpses of the report are as follows.
General information
Gland vs Akums vs Kwality: Which Pharma CDMO Has the Strongest Growth Pipeline?
USFDA issues warning letter to Aurobindo Pharma’s Telangana facility; stock dips 2 pc
Intellectual Property
Accord Healthcare Limited v Novartis AG -UK High Court Decision
- Skilled Team: The Court accepted Accord’s legal position that obviousness could be evaluated from the perspective of either a skilled team developing treatments for hypertension or one developing treatments for heart failure, noting that broad product claims spanning multiple fields must not impede uninventive developments in either.
- State of the Art (Priority Date: 17 January 2002): While angiotensin receptor blockers (ARBs, like valsartan) and ACE inhibitors (ACEis) were established, interest in neutral endopeptidase inhibitor (NEPi) monotherapy had faded due to clinical failures. The field was heavily focused on single-molecule vasopeptidase inhibitors (e.g., omapatrilat), which combined ACE and NEP inhibition but carried an uncertain risk of severe angio-oedema.
- No Class Effect for NEPis: The Court found as CGK that ARBs were largely interchangeable within their class, but NEPis were not; because NEP is an enzyme that degrades diverse vasoactive peptides, each NEPi required individual evaluation. Critically, the CGK contained no suggestion to combine an ARB with a NEPi.
- Accord argued that the Patent Application lacked hard experimental data and contained merely broad, prophetic statements.
- Applying the Warner-Lambert standard, the Court held that numerical data are not strictly mandatory. Taken as a whole, the specification provided a qualitative disclosure that the specific combination of valsartan and sacubitril had been tested in animal hypertension models with positive therapeutic effects. The disclosure satisfied the modest legal standard of ab initio plausibility.
- Ksander (1995): Disclosed the synthesis, potency, and animal pharmacokinetics of sacubitril (and its active metabolite sacubitrilat). The Court rejected Accord's obviousness case, ruling that Ksander provided no hint toward combination therapy. Accord’s step-by-step reasoning (that NEPi monotherapy failed due to RAAS activation, necessitating an ARB) was overly simplistic and hindsight-driven. RAAS activation is the triggering of the renin-angiotensin-aldosterone system, a hormone pathway that raises low blood pressure and fluid levels. It happens when the kidneys sense low blood flow, low salt, or stress, releasing renin to narrow blood vessels and force the body to hold onto water and salt.
- Trippodo (1995): Disclosed concurrent administration of an ARB (SR 47436) and a NEPi (SQ-28603) in a cardiomyopathic hamster model. The Court found that Trippodo utilised the ARB strictly as an experimental "probe" to study bradykinin mechanisms, not as a proposed therapy. Moreover, Trippodo’s data favoured ACEi/NEPi combinations over ARB/NEPis.
- Literature Search and NEPi Selection: Because there was no class effect for NEPis, a routine literature search would not have rendered sacubitril an obvious selection from among numerous potential candidates.
- Collocation (Sabaf / Illumina): The Court rejected Accord's claim that Entresto was a mere uninventive juxtaposition of two known drugs. The Patent demonstrated an empirical, functional interaction where valsartan counteracts the compensatory RAAS activation triggered by sacubitril, "unlocking" its therapeutic efficacy.
- Arbitrary Selection (Dapagliflozin): The Court held that demonstrating an actual, verified technical effect for a specific combination chosen from a broad conceptual class constitutes a genuine technical contribution over disclosures like Darrow.
- The Court cited Dapagliflozin (which applied the UK Supreme Court's Warner-Lambert standard) to determine whether a patent specification must provide hard numerical data or if qualitative statements of animal testing suffice to establish ab initio plausibility. Accord argued that selecting valsartan and sacubitril from broader classes of ARBs and NEPis ( prior art patent publication, specifically EP 498 361) was a mere "arbitrary selection" without an inventive technical advance. The judge analysed the Court of Appeal's rulings in Dapagliflozin on arbitrary selections, ultimately distinguishing the present case by noting that unlike Dapagliflozin, Novartis provided experimental results showing an actual, verified technical effect for the specific combination.
