📋 Executive Summary
Novartis enters 2026 at a critical crossroads, balancing looming patent expiries with an ambitious pipeline-driven renewal strategy. Key blockbusters face near-term loss of exclusivity (LOE) – notably heart failure drug Entresto (global sales $7.8B in 2024) which goes generic by mid-2025, and Xolair (omalizumab) with biosimilars launching in 2025. Yet, Novartis leadership projects confidence that new growth engines and fiscal discipline will more than compensate, targeting mid-single-digit annual sales growth through the latter 2020s.
💡 "Novartis is turning obstacles into opportunities – divesting its Sandoz generics unit to sharpen focus, doubling down on cutting-edge therapies like radioligand treatments, gene therapies, and niche immunological drugs."
The company has completed a strategic transformation into a pure-play biopharma company, spinning off Sandoz in late 2023 to concentrate resources on innovative medicines. This leaner structure has already yielded results: core operating margins reached 41.2% in the first nine months of 2025 – hitting the 40%+ margin goal two years ahead of plan.
Entresto 2024 Sales ($B)
Core Operating Margin (%)
Pipeline Catalysts by 2026
Projected Sales CAGR (%)
🎯 Key Strategic Priorities for 2026
Expanding Pluvicto into earlier-stage prostate cancer and developing next-gen actinium-225 therapies
15+ potential approvals or pivotal readouts expected by 2026 across core therapeutic areas
Launching remibrutinib across multiple indications to offset Xolair biosimilar impact
Pelacarsen and Leqvio outcomes data to establish post-Entresto cardiovascular leadership
⏰ Patent Cliff Timeline (2025–2028)
Novartis faces a "patent cliff" wave from 2025 to 2028 that will see several major revenue drivers lose exclusivity. The cumulative impact is significant: Entresto and Xolair alone contributed an estimated $10+ billion in 2024 sales, and their loss will pressure Novartis' Immunology and Cardiovascular franchises.
Key Patent Expiry Timeline
Ilaris & Tasigna
Ilaris (~$0.7B) lost protection; Tasigna opened to generic competition in late 2024
Entresto & Xolair
Entresto ($7.8B) faces U.S. generics by July 2025; Xolair biosimilars launch Q4 2025; Promacta & Tasigna generics intensify
Jakavi
Jakavi (~$0.5B) loses exclusivity ex-US; Focus shifts to managing 2025 fallout
Breather Period
No major LOEs scheduled – crucial window for new launches to ramp up; Preparation for Cosentyx 2029 LOE begins
LOE Revenue at Risk (2025-2028)
Estimated revenue impact from key patent expiries
Novartis Revenue Mix Shift
Projected portfolio transformation 2024 vs 2028
⚠️ Revenue Concentration Risk
These cliffs underscore a critical risk: Novartis has been highly reliant on a few blockbusters in each therapy area. Entresto and Cosentyx were among Novartis' top sellers, and together with drugs like Kesimpta and Kisqali, they form a large share of current revenue.
The spin-off of Sandoz means Novartis no longer internally recaptures any revenue through generic subsidiaries – all erosion goes to external competitors. This raises the stakes but also frees Novartis to focus purely on novel therapeutics.
✓ Defensive Win: In early 2025, Novartis settled a patent challenge on Kisqali® (ribociclib), ensuring U.S. exclusivity until at least 2031 – protecting the oncology portfolio as Pfizer's Ibrance nears its own 2027 LOE.
⚖️ Regulatory Outlook (U.S., EU & Global)
The regulatory horizon for 2025–2026 is packed with potential approvals, submissions, and critical health authority decisions that will define Novartis' near-term success. The company is pursuing expansion across radioligand therapy, immunology, cardiovascular, and gene therapy domains.
✅ Major Approvals Expected (2025–2026)
Pluvicto® Label Expansion
FDA decision expected H1 2025 for pre-chemotherapy use in mCRPC. Already approved for late-line prostate cancer (over $1.04B in first 9 months of 2024), this expansion could significantly enlarge the patient pool.
High ProbabilityItvisma® (OAV-101 Intrathecal)
FDA approved late 2025 – innovative intrathecal formulation of Zolgensma for older SMA patients. EU approval expected 2026. This expands the SMA franchise beyond infants.
Approved US 2025Remibrutinib (BTK Inhibitor)
NDA filing expected H1 2025 for chronic spontaneous urticaria (CSU). Could launch in 2026 as first-to-market BTK inhibitor for hives, offering an oral alternative to injectable Xolair.
Filing 2025Vanrafia® (Atrasentan)
Accelerated FDA approval achieved April 2025 for IgA nephropathy – notably without REMS requirement, differentiating from competitor sparsentan. Full approval submission with kidney function data expected 2026.
Approved 2025📋 Key Submissions & Filings (2025–2026)
| Asset | Indication | Expected Milestone | Strategic Importance |
|---|---|---|---|
| Ianalumab (VAY736) | Sjögren's Syndrome | Ph3 data ~2025; Filing ~2026 | First-in-class for Sjögren's – opens new market |
| Pelacarsen | CV Risk (Lp(a)) | Outcomes data late 2025 | First approved Lp(a)-lowering therapy if positive |
| Remibrutinib | Multiple Sclerosis | Ph3 readout 2026 | Oral alternative to anti-CD20 antibodies |
| Abelacimab | Atrial Fibrillation | Ph3 data ~2025 | Next-gen anticoagulant with less bleeding risk |
| Kisqali® | Early Breast Cancer | Global approvals 2024-25 | Doubles addressable patient population |
🔒 Safety, Compliance & Policy Considerations
☢️ Radioligand Manufacturing
After 2022 supply constraints, Novartis invested heavily – adding sites in Spain, New Jersey, and California. By 2025, Pluvicto supply is no longer constrained. The complexity also deters generic competition, as radioligands are exceptionally hard to replicate.
📋 REMS Strategy
Getting Vanrafia approved without a REMS was a strategic win, differentiating from Travere's sparsentan which requires liver monitoring. This demonstrates Novartis' ability to build regulatory advantage through safety data.
💰 U.S. IRA Impact
Entresto was selected among the first 10 drugs for Medicare price negotiation in 2026. While generics may make this moot, future rounds could target Cosentyx or other drugs, adding regulatory/commercial risk layers.
🇪🇺 EU Policy Changes
The EU's pharma legislative overhaul (expected 2025-26) might shorten exclusivity periods unless companies launch widely across member states. Novartis will need to launch products in smaller EU countries faster to secure full exclusivity.
🧪 Pipeline & Clinical Momentum Analysis
Novartis' late-stage pipeline in 2025–2026 reflects a broad and ambitious effort to rejuvenate its portfolio ahead of the patent cliffs. The company has touted "15+ potential approvals or pivotal readouts by 2026" across its core therapeutic areas, with 8+ assets having multi-billion dollar potential expected to launch by mid-decade.
💡 "Novartis expects to realize the $10 billion business potential of its radioligand candidates in trials and driving consistent mid-term growth despite LOEs."
☢️ Radioligand Therapies & Oncology
Pluvicto® (Lu-177 PSMA-617)
Already a commercial success ($1.04B in first 9 months of 2024), expansion into earlier lines is a top priority. The PSMAfore Phase 3 trial met endpoints for pre-chemo use, with FDA decision expected H1 2025. Additional trials (PSMAddition) in hormone-sensitive prostate cancer could lead to submissions by 2026.
Next-Gen Actinium-225 Platforms
Novartis is developing actinium-225-based PSMA therapies (AAA617, AAA802) with greater potency and longer half-life. Phase 1 trials began in 2024. The company also acquired Mariana Oncology for an actinium radioligand in small cell lung cancer. These aim to deliver a "next wave" by ~2028-2030.
Kisqali® (Ribociclib) – CDK4/6 Inhibitor
NATALEE Phase 3 success in early breast cancer significantly reduces recurrence. Global approvals for adjuvant use expected 2024-25, potentially doubling addressable patient population. With U.S. patent secure to 2031, Kisqali is a cornerstone of the oncology strategy – projected as a multi-billion franchise through the 2020s.
Pluvicto Revenue Growth
Quarterly revenue trajectory ($M)
Kisqali Market Position
CDK4/6 inhibitor market share evolution
🧬 Immunology, Dermatology & Neuroscience
Remibrutinib – Multi-Indication BTK Inhibitor
One of Novartis' most versatile pipeline assets, in trials for CSU, CINDU, MS, HS, and Food Allergy. Two Phase 3 studies in CSU met goals – NDA submission expected 2025 with approval in 2026. MS Phase 3 readout due 2026. Could yield multiple product launches from one molecule between 2025-2027.
Ianalumab (VAY736) – Anti-BAFF Receptor Antibody
Aiming to be the first targeted therapy for Sjögren's syndrome (SjD) – an autoimmune disease with no approved treatments. Also in trials for SLE, lupus nephritis, ITP, and warm AIHA. Phase 3 filing expected ~2026. Could be a game-changer with multi-indication reach across rheumatology and hematology.
Kesimpta® (Ofatumumab) – MS Franchise
Competing with Roche's Ocrevus in MS with at-home administration advantage. Almost $1B in 2024 sales with continued growth expected. Novartis emphasizes convenience and testing less frequent dosing to differentiate.
Remibrutinib Multi-Indication Pipeline
Development stage by indication
MS Market Landscape
Anti-CD20 MS therapies comparison
❤️ Cardio-Renal & Hematology
Pelacarsen (TQJ230) – Lp(a) Lowering
One of Novartis' highest-profile Phase 3 bets. The pivotal trial in secondary CV prevention (patients with high Lp(a) and CVD) will report late 2025 or early 2026. A positive outcome would make pelacarsen the first-ever Lp(a)-lowering therapy with outcome benefit – analysts see multi-billion sales potential.
Leqvio® (Inclisiran) – siRNA for LDL-C
Already approved for LDL-C lowering with ~$0.3B in 2024 sales. ORION-4 outcomes trial reading 2026-27 will determine if Leqvio can challenge rival PCSK9 injectables. Novartis' bi-annual injection model (given by HCPs) ensures adherence advantage.
Abelacimab (MAA868) – Factor XI Antibody
Novel anticoagulant via Anthos (Novartis stake). Phase 3 in atrial fibrillation stroke prevention vs rivaroxaban due 2025. If positive, could be filed in 2026 as next-gen safer anticoagulant with less bleeding risk. Competes with J&J/BMS's milvexian in the factor XI space.
Fabhalta® (Iptacopan) & Vanrafia® (Atrasentan)
Fabhalta (factor B inhibitor) won FDA approval for PNH and IgA nephropathy – expanding into myasthenia gravis with Phase 3 reporting 2027. Vanrafia secured accelerated approval in IgAN without REMS, giving competitive edge over Travere's sparsentan.
CV Portfolio Evolution
Projected revenue transition from Entresto
Pelacarsen Lp(a) Reduction
Mean Lp(a) reduction from baseline (%)
⚔️ Competitive Landscape Overview
The pharmaceutical battlefield in 2025–2026 will see Novartis defending its turf against formidable competitors across each major therapeutic area. Radioligand rivals are racing into Novartis' turf, biosimilars are nipping at immunology and oncology stalwarts, and next-gen cardiovascular therapies seek to capitalize on post-LOE voids.
☢️ Radioligand & Oncology Competition
Novartis currently leads in radiopharmaceuticals with Lutathera and Pluvicto, but other pharma giants are rapidly entering:
Eli Lilly
Acquired Point Biopharma (2023). Advancing PNT2001 – a next-gen Ac-225 PSMA radioligand in first-in-human trials (early 2024). Products likely won't hit market until late-decade, but narrowing Novartis' window.
Bayer
Pioneer with Xofigo (radium-223). Acquired Noria Therapeutics assets yielding BAY 3563254 (Ac-225 PSMA) in Phase 1 (2024). Partnered with PanTera for isotope supply. Expect Bayer vs. Novartis showdown ~2027+.
Bristol Myers Squibb
Largest radiopharma deal – RayzeBio acquisition for $4.1B (2023). RYZ101 (Ac-225 peptide for NETs) in Phase 3. Going after Novartis's neuroendocrine franchise (Lutathera). Competitive Phase 3 race in NETs expected.
AstraZeneca
Fusion Pharma buy (2024). FPI-2265 (Ac-225 PSMA) in Phase 2 with data H2 2025. Set goal for radioconjugates to be a big revenue driver by 2030. Strong oncology footprint means quick integration if successful.
💡 Strategic Implication: Novartis' window to capitalize on Pluvicto's lead is a few years. The more hospitals get on board with Novartis' RLT, the harder it is for competitors to displace them later. Generic radioligands are unlikely soon due to manufacturing complexities.
🛡️ Immunology & Dermatology Battleground
Cosentyx vs the Field
Cosentyx (IL-17A inhibitor) rivals include Eli Lilly's Taltz® (similar patent timeline), plus encroachment from IL-23 inhibitors (Skyrizi, Tremfya) and JAK inhibitors (Rinvoq). BMS's deucravacitinib (Sotyktu), an oral TYK2 inhibitor, launched 2023 for psoriasis.
Xolair & Asthma/Allergy
Anti-IL5 drugs (GSK's Nucala) and Dupixent (Sanofi/Regeneron) have taken big market share. Xolair biosimilars (Celltrion's first approved) hit in 2025 – franchise will erode quickly. Remibrutinib positioned to replace Xolair in urticaria.
MS Market Dynamics
Kesimpta competes with Roche's Ocrevus (both target CD20). New MS entrants include BTK inhibitors: Sanofi's tolebrutinib (delayed by safety) and Merck's evobrutinib (paused). If remibrutinib's MS trials succeed, could leapfrog competitors. Roche launching subcutaneous Ocrevus could negate Kesimpta's convenience edge.
❤️ Cardiovascular & Metabolic Shifts
Heart Failure Post-Entresto
Generics from firms like MSN will swiftly take market share via payer substitution. SGLT2 inhibitors (Jardiance, Farxiga) have become part of standard HF therapy. By 2026, generic ARNI will be commonplace, and Novartis will attempt to fill revenue with novel CV drugs.
Hyperlipidemia Landscape
Leqvio competes with Amgen's Repatha and Sanofi's Praluent (PCSK9 mAbs). New competitor: Merck's oral PCSK9 inhibitor (MK-0616) in Phase 3 – by 2026-27 an oral option could disrupt Leqvio's niche. Novartis emphasizes bi-annual injection adherence advantage.
Renal Disease Competition
In IgAN, Novartis (via Chinook) goes head-to-head with Travere's Sparsentan (Filspari). Travere has a year+ head start but Vanrafia's no-REMS advantage is significant. In PNH, Fabhalta competes with AstraZeneca's Ultomiris as an oral alternative.
📊 Competitive Position by 2026
Clear Leader
- • Radioligand therapy (Pluvicto)
- • SMA gene therapy (Zolgensma/Itvisma)
- • Early breast cancer (Kisqali)
Strong Contender
- • Immunology (BTK + IL-17)
- • Multiple Sclerosis
- • Renal diseases
Defensive Position
- • Respiratory/Allergy (Xolair decline)
- • Mature oncology (Tasigna, Gleevec)
- • Heart failure (Entresto LOE)
🎯 Strategic Positioning & Business Outlook
As 2026 dawns, Novartis finds itself transformed into a more focused, innovative medicines company after years of restructuring and the Sandoz generics spin-off. This strategic positioning carries opportunities for agility and growth, as well as challenges in sustaining momentum through the patent cliff period.
🏢 Post-Sandoz Focus & Financials
The separation of Sandoz in late 2023 left Novartis as a pure-play pharma developer with a leaner portfolio centered on high-margin, novel drugs. Benefits were immediate: core operating margin of 41.2% in the first nine months of 2025 – hitting the 40%+ goal two years ahead of plan.
Annual R&D Investment
Free Cash Flow (2024)
Share Buyback Authorization
Financial outlook for 2026 projects mid- to high-single-digit net sales growth and high-single to low-double-digit core income growth. R&D resources (~$9B/year) are now concentrated on core areas: Oncology, Immunology, Cardiovascular, Neuroscience, and Hematology.
🌍 Geographic Mix & Strategy
🇺🇸 United States (35-40%)
Critical for growth – higher pricing, faster uptake. U.S.-first commercial focus with separate organizational unit. Risk: Medicare pricing reforms (IRA impact).
🇪🇺 Europe (~30%)
Strong traditional presence, particularly Germany, UK, Switzerland. Slower growth due to price controls. Must launch in smaller EU countries faster for full exclusivity under new legislation.
🇨🇳 China & Emerging
China is top-5 market with rapid growth for Entresto, Cosentyx, Kesimpta. Risk: NRDL negotiations demand steep discounts. Accept lower margins for volume and growth.
🤝 M&A and Licensing Strategies
Novartis has signaled openness to "bolt-on" acquisitions (roughly $2–5B) to strengthen its pipeline. With ~$16B free cash flow, the company has firepower for several deals without stressing the balance sheet.
📈 2026 Scenario Forecasts
🎯 Upside Case
Pipeline delivers on all cylinders. Remibrutinib, ianalumab, pelacarsen all approved and launching successfully. Pluvicto doubles with new indications.
Operating margins stay ~40%
⚖️ Base Case
2026 is a transition year – sales dip slightly or stay flat as Entresto erosion hits. New products ramping but may not fully offset billions lost.
Valley in 2025-26, re-acceleration 2027
⚠️ Downside Case
Major pipeline setbacks – pelacarsen fails or safety issues delay remibrutinib. LOEs not compensated, forcing cost-cutting.
Emergency acquisitions may be needed
💡 Actionable Insights
Key takeaways for regulatory affairs teams, competitive intelligence professionals, and pharma executives seeking to learn from Novartis' playbook.
⚖️ For Regulatory Affairs Professionals
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Proactive Engagement: Novartis' success with Itvisma (lifting FDA hold) and Vanrafia (no REMS) demonstrates the value of addressing regulatory concerns head-on with robust data. Use FDA's Breakthrough or PRIME pathways when applicable.
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Manufacturing Readiness: Having additional manufacturing sites pre-approved can be a lifesaver. Conduct rigorous pre-approval inspections (mock audits), especially for novel modalities like radioligands.
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Policy Tracking: Track EU pharmaceutical legislation revisions on data exclusivity and U.S. FDA guidance on AI in clinical trials. Scenario-plan how drugs would fare if selected for Medicare negotiation.
🔍 For Competitive Intelligence Teams
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Monitor Pipeline Readouts: Build a detailed competitor catalyst calendar for 2025-2026 – Lilly's PNT2001 data, BMS/RayzeBio Phase 3 in NETs, Merck's BTK trial readouts. Anticipate competitive launches 1-2 years out.
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Biosimilar Intelligence: Track which companies are developing biosimilars for Xolair (2025) and Cosentyx (2029), their progress, pricing approaches, and quality profiles. Understand patent litigation globally.
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Benchmark Patent Cliff Strategies: Analyze how BMS, Merck, Pfizer are responding to their own cliffs. Novartis chose pipeline-driven renewal with selective bolt-ons – assess which approach works best industry-wide.
🏆 For Pharma Executives
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Partnership Opportunities: If you have a promising asset in Novartis' focus areas (oncology, immunology, cardio-renal, neuroscience, gene therapy), 2025-2026 is prime time to engage. Their need to offset LOEs means they may pay a premium for assets that can contribute by ~2027.
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Therapeutic Focus: Novartis pruned to 5 core therapeutic areas. Being best in a niche can be more valuable than broad but shallow. Consider narrowing focus like Novartis did.
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Lifecycle Management: Novartis shows how to extend product life – new indications/formulations, patent settlements (Kisqali to 2031). Plan indication expansions early, obtain patents on new uses.
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Cross-Functional Coordination: Consider a "Patent Cliff SWAT team" – use CI to predict competitor timing, have Regulatory get new drugs approved by key dates, align sales force realignment with LOE timing.
🎯 Conclusion
Novartis in 2026 is poised to emerge from its patent cliff trough by leaning on its rich pipeline and sharpened strategic focus. The company's own outlook suggests confidence – expecting to "grow through" the LOE phase while improving margins simultaneously.
If Novartis executes well, by end of 2026 we could be calling it a successful case of big pharma reinvention. If it stumbles, it will serve as a cautionary tale of how patent cliffs can still bite even the best-prepared companies.
Given the data and Novartis' track record, cautious optimism is warranted – they likely have just enough in the tank to fuel growth through 2028, though it may be a close race with the patent cliff clock.