List of Excipients in Branded Drug STELARA

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STELARA Excipient Strategy, Formulation Patents, Biosimilar Risk and Commercial Opportunities

Last updated: September 24, 2026

STELARA (ustekinumab) is a monoclonal antibody marketed by Janssen Biotech for plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. Its commercial formulation uses a conventional biologic excipient system: sucrose for tonicity and stabilization, histidine-based buffering, polysorbate 80 for interfacial protection, and water for injection. The principal commercial opportunity is not a novel excipient replacement. It is the development of biosimilar, device-enabled, preservative-free, high-concentration, manufacturing-efficient and geographic-market formulations that satisfy the FDA and other regulators' comparability standards.

Janssen reported STELARA sales of approximately $10.9 billion in 2023, making the product one of the largest biologic revenue pools exposed to biosimilar erosion.[1] FDA approval of the first ustekinumab biosimilar, Wezlana (ustekinumab-auub), confirmed that the market has moved from patent protection toward launch execution and payer access.[2]

What excipients are used in the STELARA formulation?

The US STELARA formulation contains sucrose, L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80 and water for injection.[3]

Product presentation	Ustekinumab strength	Key excipients	Administration
Pre-filled syringe	45 mg/0.5 mL	Sucrose, histidine, histidine hydrochloride, polysorbate 80	Subcutaneous
Pre-filled syringe	90 mg/1.0 mL	Sucrose, histidine, histidine hydrochloride, polysorbate 80	Subcutaneous
Single-dose vial	45 mg/0.5 mL	Sucrose, histidine, histidine hydrochloride, polysorbate 80	Subcutaneous
Single-dose vial	130 mg/26 mL	Sucrose, histidine, histidine hydrochloride, polysorbate 80	Intravenous infusion

The product is a preservative-free aqueous solution. The formulation has a mildly acidic pH, generally reported in the range of approximately 5.5 to 6.5 depending on presentation and product documentation.[3,4]

What function does each STELARA excipient perform?

Excipient	Primary technical role	Commercial relevance
Sucrose	Stabilizes the antibody during freezing, thawing, storage and shipment; contributes to tonicity	Creates demand for pharmaceutical-grade sucrose and supports formulation similarity
Histidine	Provides buffering capacity near the product's target pH	Reduces pH-driven aggregation and degradation
Histidine hydrochloride monohydrate	Complements the histidine buffer system	Helps control pH and ionic conditions
Polysorbate 80	Limits adsorption and aggregation at air-liquid and container-liquid interfaces	Creates a major control point for peroxide, hydrolysis and degradation impurities
Water for injection	Solvent and carrier	Requires control of bioburden, endotoxin and particulate quality

The formulation is strategically conservative. It uses widely accepted biologic excipients with established regulatory histories. That reduces formulation risk but limits the ability to obtain strong composition-of-matter protection around the excipient combination alone.

How strong is the STELARA excipient and formulation patent estate?

The core commercial protection for STELARA has historically come from the ustekinumab molecule and antibody-related patent rights, not from a highly differentiated excipient platform. Biologic products are not listed in the FDA Orange Book. Relevant US patent and exclusivity information is reviewed through the Purple Book, patent litigation records and biologics license documentation.[5]

The principal commercial risks are:

1. Biosimilar approval under the 351(k) pathway.
2. Expiration or settlement of antibody and method-of-use patents.
3. Design-around of formulation claims.
4. Patent litigation involving dosing regimens, indications, devices or manufacturing processes.
5. Substitution pressure from lower-cost infliximab, adalimumab and other biologics in inflammatory disease.

An excipient claim covering sucrose, histidine buffer and polysorbate 80 would generally face weak validity and enforcement prospects if the combination is conventional and predictable. Stronger claim strategies would require measurable technical advantages, such as improved high-concentration stability, reduced subvisible particles, reduced oxidation, lower polysorbate degradation, longer refrigerated shelf life or improved delivery-device compatibility.

What formulation patents could protect a STELARA follow-on product?

Commercially useful formulation claims may cover:

• A defined protein concentration and pH range.
• Specific sucrose-to-protein ratios.
• Reduced polysorbate concentration.
• Alternative surfactants, such as polysorbate 20 or poloxamers.
• Low-peroxide or stabilized polysorbate systems.
• Arginine, trehalose, methionine or other stabilizers.
• High-concentration subcutaneous formulations.
• Room-temperature storage or extended excursion stability.
• Reduced aggregation after agitation, shipping or autoinjector delivery.
• Compatibility with siliconized syringes, elastomeric closures or wearable injectors.
• Lyophilized or reconstituted presentations.

The strongest formulation portfolios combine composition claims with analytical specifications and process controls. A claim directed only to a familiar excipient combination is easier to challenge and design around.

When does STELARA lose exclusivity and when can generics or biosimilars launch?

STELARA does not face conventional small-molecule generic entry. Its competitive threat comes from biosimilars and potentially interchangeable biosimilars.

Milestone	Date or status
FDA approval of STELARA	September 2009
Twelve-year US reference-product exclusivity	Expired in 2021
First FDA-approved ustekinumab biosimilar	Wezlana, October 2024
First US commercial biosimilar launch	Scheduled under settlement arrangements beginning in 2025
Traditional small-molecule Orange Book generic pathway	Not applicable
Principal regulatory pathway	FDA 351(k) biosimilar pathway

FDA approved Wezlana, manufactured by Amgen, as a biosimilar to STELARA for the same major disease areas covered by the reference product, subject to product-specific labeling and regulatory requirements.[2]

What is the Orange Book status of STELARA?

STELARA is not an Orange Book-listed small-molecule product. The Orange Book does not provide the primary patent framework for therapeutic biologics. Biosimilar developers evaluate the Purple Book, biologics patent disclosures, the Biologics Price Competition and Innovation Act patent-exchange process, and litigation under the Hatch-Waxman-like patent dispute framework applicable to biologics.[5,6]

Which companies are challenging STELARA's market position?

Amgen is the clearest identified commercial entrant through Wezlana. Other major biologics manufacturers and biosimilar specialists have pursued ustekinumab programs or settlement-based launch strategies in different jurisdictions.

Company	Product or program	Strategic position
Janssen Biotech	STELARA	Reference product and patent holder
Amgen	Wezlana, ustekinumab-auub	FDA-approved biosimilar; major US competitor
Sandoz	Ustekinumab biosimilar program	Global biosimilar competition
Celltrion	Ustekinumab biosimilar program	Manufacturing scale and immunology commercial infrastructure
Samsung Bioepis	Ustekinumab biosimilar program	Large-scale biologics development and regional licensing potential
Teva and other regional developers	Ustekinumab programs or partnerships	Potential price competition and local-market entry

The number of approved products and commercial launch dates varies by jurisdiction. The competitive effect will depend on interchangeability, payer contracting, channel access, supply reliability and net pricing rather than approval count alone.

What excipient opportunities exist for STELARA biosimilars?

The highest-value opportunity is a differentiated formulation that reduces total cost of ownership without creating a clinically meaningful difference from STELARA.

High-concentration subcutaneous formulations

A higher-concentration product could reduce injection volume and support autoinjectors, on-body delivery systems or less painful administration. The principal technical barriers are viscosity, aggregation, particle formation, syringeability and device-force requirements.

A developer could pursue:

• Ustekinumab concentrations above the reference product's marketed subcutaneous concentration.
• Reduced injection volume.
• Compatibility with 1 mL or 2.25 mL prefilled syringes.
• Autoinjector or wearable delivery.
• Longer room-temperature stability.
• Reduced injection-site discomfort.

These changes may create new formulation and device patents, but they also increase analytical and clinical bridging requirements.

Surfactant replacement or optimization

Polysorbate 80 can degrade through hydrolysis and oxidation, generating free fatty acids, peroxides and particles. A biosimilar developer could evaluate polysorbate 20, poloxamer 188 or a low-peroxide polysorbate 80 grade. The commercial advantage would be strongest if the alternative reduces particle formation or improves storage robustness without changing immunogenicity risk.

Surfactant changes require careful assessment of:

• Protein aggregation.
• Subvisible and visible particles.
• Oxidative degradation.
• Container interaction.
• Silicone oil compatibility.
• Freeze-thaw stability.
• Comparability of degradation pathways.

The replacement of polysorbate 80 is technically attractive but carries more regulatory risk than optimizing its grade, concentration or manufacturing controls.

Alternative sugar and amino-acid systems

Trehalose may replace sucrose in some biologic formulations, while methionine can provide oxidative protection and arginine can influence solubility and aggregation. These systems may support new patent claims, but they must demonstrate a material performance advantage over the reference formulation.

A practical development strategy is to screen:

1. Sucrose versus trehalose.
2. Histidine versus phosphate or acetate buffers.
3. Polysorbate 80 versus polysorbate 20 or poloxamer 188.
4. Methionine or other antioxidants.
5. Different pH and ionic-strength windows.

The commercial target should be a narrower, evidence-supported formulation rather than a broad list of conventional excipients.

What manufacturing and IP barriers affect STELARA biosimilars?

Ustekinumab manufacturing creates barriers beyond the final formulation. Critical issues include:

• Stable high-yield Chinese hamster ovary cell lines.
• Control of glycosylation and charge variants.
• Removal of aggregates and process-related impurities.
• Viral clearance.
• Control of host-cell proteins and residual DNA.
• Consistent potency against interleukin-12 and interleukin-23 pathways.
• Long-term stability under refrigerated and shipping conditions.
• Container-closure integrity.
• Scale-up without changes in critical quality attributes.

A biosimilar applicant must establish high similarity through structural, functional, analytical and, where required, clinical evidence. Excipients are only one part of the comparability package. A formulation that differs from STELARA may remain approvable, but the developer must show that the difference does not affect safety, purity or potency.

Manufacturing patents may be stronger than basic excipient claims if they cover a specific cell-culture process, purification sequence, impurity-control method or high-concentration fill-finish process. These patents can create licensing opportunities for contract development and manufacturing organizations.

What licensing deals and commercial structures are likely?

The main licensing opportunities include:

• Regional commercialization rights for ustekinumab biosimilars.
• Device partnerships for autoinjectors and wearable injectors.
• Excipient supply agreements with biologics-grade material suppliers.
• Contract manufacturing for drug substance or drug product.
• Co-development of high-concentration or low-volume presentations.
• Distribution arrangements in markets with rapid biosimilar substitution.
• Portfolio transactions combining ustekinumab with other immunology biosimilars.

Reference-product settlements can materially affect launch timing. Janssen has entered into agreements with biosimilar developers that determine permitted US entry dates and other commercial terms. The exact economics and launch conditions depend on each agreement and may not be fully public.[7]

What revenue exposure does STELARA face from biosimilars?

STELARA's revenue exposure is unusually large because the product has substantial sales in chronic, high-cost indications. The erosion pattern will likely differ by segment:

Segment	Biosimilar substitution risk	Key commercial driver
Dermatology	Moderate to high	Payer formulary placement and self-injection convenience
Psoriatic arthritis	Moderate	Prescriber loyalty and treatment sequencing
Crohn's disease	High	Hospital and specialty-pharmacy contracting
Ulcerative colitis	High	Net price and comparative effectiveness
Intravenous induction	Moderate	Infusion-center economics and procurement
Subcutaneous maintenance	High	Device, adherence and patient support

Janssen can defend share through contracting, service programs, indication-specific evidence and device convenience. Biosimilar companies can compete through lower net price, broader distributor access, interchangeable status and supply guarantees.

What generic launch scenarios exist for STELARA?

Three commercial scenarios are most relevant.

Early multi-biosimilar competition

Several products launch within a short period. Net prices decline rapidly, payer formularies narrow and supply reliability becomes a decisive differentiator.

Staged entry led by one major biosimilar

A first entrant obtains preferred access and captures meaningful share before later entrants arrive. The first entrant can sustain higher pricing if it has interchangeable status, strong distribution and a differentiated device.

Limited substitution with reference-product retention

STELARA maintains substantial share because of prescriber preference, patient stability, contracting or device advantages. In this scenario, biosimilars compete mainly through new starts and price-sensitive accounts.

For excipient suppliers, the third scenario still supports commercial opportunity because every biosimilar developer must qualify raw materials, establish supply continuity and meet biologic-grade quality specifications.

How does STELARA compare with competing biologic patent estates?

STELARA's commercial profile differs from Humira and other immunology biologics.

Product	Active ingredient	Primary competition	Formulation opportunity
STELARA	Ustekinumab	Ustekinumab biosimilars; IL-17, IL-23 and TNF competitors	High-concentration SC, devices, surfactant optimization
Humira	Adalimumab	Multiple adalimumab biosimilars	High-concentration and citrate-free formulations already established
Skyrizi	Risankizumab	Future IL-23 biosimilars and immunology competitors	Device and dosing convenience
Tremfya	Guselkumab	Future IL-23 biosimilars	Low-volume delivery and maintenance convenience
Entyvio	Vedolizumab	Vedolizumab biosimilars	IV-to-SC conversion, device and stability

STELARA's broad mechanism, four major indications and established subcutaneous maintenance regimen create a large target for biosimilar manufacturers. Its conventional excipient system also gives developers multiple ways to produce a comparable or differentiated product without relying on a highly unusual excipient technology.

Key Takeaways

• STELARA uses sucrose, histidine, histidine hydrochloride, polysorbate 80 and water for injection.
• The excipient system is conventional, stable and commercially reproducible.
• The strongest formulation opportunities involve high concentration, low injection volume, device compatibility, improved surfactant stability and extended storage.
• Basic excipient-combination claims are likely weaker than claims covering measurable stability or delivery advantages.
• FDA-approved biosimilar competition has begun with Amgen's Wezlana.
• The relevant US framework is the Purple Book and the 351(k) pathway, not the Orange Book.
• Ustekinumab's large revenue base supports opportunities in biosimilars, excipients, fill-finish, devices, manufacturing and regional licensing.
• The main barriers are analytical similarity, manufacturing consistency, immunogenicity control, patent settlements and payer access.

FAQs

What is the main excipient opportunity for a STELARA biosimilar?

The most practical opportunity is a high-concentration subcutaneous formulation with lower injection volume and compatibility with an autoinjector or wearable device.

Can a company patent sucrose and polysorbate 80 in a ustekinumab product?

A broad claim covering conventional sucrose and polysorbate 80 use would likely be difficult to sustain without a demonstrated technical effect. Narrow claims tied to concentration, pH, stability, particle control or device compatibility have stronger commercial potential.

Is STELARA protected by Orange Book patents?

No. STELARA is a biologic. Its US regulatory and patent analysis relies on the Purple Book, biologics patent disclosures, FDA records and patent litigation proceedings.

What is the biggest manufacturing barrier for ustekinumab biosimilars?

The primary barrier is consistent production of a highly similar antibody with controlled glycosylation, charge variants, aggregates, potency and impurity profiles at commercial scale.

Will biosimilars eliminate STELARA revenue?

Biosimilars are likely to reduce net pricing and market share, but the degree of erosion will depend on launch timing, interchangeability, payer contracting, device differentiation, prescriber behavior and supply reliability.

References

1. Johnson & Johnson. (2024). 2023 annual report.
2. U.S. Food and Drug Administration. (2024). FDA approves first interchangeable biosimilar to Stelara.
3. U.S. Food and Drug Administration. (2024). STELARA prescribing information. Janssen Biotech, Inc.
4. European Medicines Agency. (2024). Stelara: EPAR product information.
5. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products.
6. Biologics Price Competition and Innovation Act, Pub. L. No. 111-148, §§ 7001-7003, 124 Stat. 119 (2010).
7. Johnson & Johnson. (2024). Janssen announces settlement agreements relating to ustekinumab biosimilar litigation.