The Golden Age of Subcutaneous Biologics (2025–2035)
- Tribridge BioCapital Research Team
- Jan 15
- 14 min read
Updated: Jan 24
Summary
The global biologics market is heading toward a US$1 trillion valuation by 2035, led by the rapid rise of subcutaneous (SC) antibody administration. Growing from $60B to $233B (~14.5% CAGR), SC delivery is replacing traditional intravenous (IV) infusion as the industry standard. This "Golden Age" allows Big Pharma to combat “patent cliffs” by “resetting the clock” on exclusivity through SC reformulations of multi-billion-dollar franchises.
The shift relies on two technological pillars: enzymatic permeation enhancement (using hyaluronidase to reduce tissue viscosity) and ultra-high concentration formulation. Platforms like Halozyme’s ENHANZE® and Alteogen’s ALT-B4 now enable the delivery of large-volume biologics in minutes rather than hours. This has triggered a "hockeystick" adoption curve for oncology anchors like Keytruda, Opdivo, and Darzalex.
Economically, this creates a convenience flywheel that reclaims clinic "chair time," boosts patient throughput, and cuts systemic waste. Regionally, the Asia-Pacific region, led by South Korean firms like Alteogen and Celltrion, is challenging Western monopolies with innovative "Bio-betters."
By 2035, SC platforms will be the essential foundation for next-generation medicines like bispecifics and ADCs, offering investors a decade-long runway of high-margin growth through the most significant biologics revenue migration in history
Disclaimer: This report is intended for informational and strategic discussion purposes only. Market sizes and forecasts (2025-2035) are synthesized from publicly available research summaries and proprietary modeling; they are sensitive to market-definition scope. Readers should perform independent due diligence and channel checks before making capital allocation decisions
Part I.
The Trillion-Dollar Biologics Market and subcutaneous (SC) Enabling Technologies
By 2035, the biologics landscape will reach a $1 trillion milestone, defined by the rapid obsolescence of traditional IV infusion. Subcutaneous (SC) delivery is spearheading this expansion, with a projected 14.5% CAGR that will more than triple its market size to $233B. This “Golden Age” is not merely a growth phase, but a structural replacement of the IV standard with more efficient, high-margin SC platforms.
A. The Golden Age of SC Biologics
For decades, IV infusion was the default route for administering therapeutic proteins, largely because achieving clinical efficacy often required high doses delivered in substantial volumes. Recently, a rapid shift toward SC administration is reshaping clinical workflows, patient experience, and market competitiveness. This report reviews the global migration from IV to SC delivery between 2005 and 2035. Our analysis focuses on enabling platforms, revenue dynamics, and the health-economic implications that are creating new investment opportunities across the SC value chain.
The SC antibody biologics market is entering a high-growth phase, powered by advanced delivery technologies and large-scale IV to SC conversions by major biopharmaceutical companies. We expect adoption to continue broadening as small- and mid-sized, commercially focused biopharma entities enter this high-value sector through strategic partnerships and innovative formulation development.
While early SC enabling technology emerged in 2005, the pivotal wave of SC antibody biologics approvals accelerated after 2017, leading to the unprecedented pace seen today. This 'Hockey-Stick' momentum, an explosive upswing in regulatory milestones, signals that SC delivery has successfully cleared long-standing technical and regulatory hurdles. Big Pharma is decisively validating this IV to SC shift by transitioning its highest-value franchises (e.g., Keytruda, Darzalex, and Opdivo) to SC formats. This strategy allows originators to defend against looming patent cliffs and 'reset the clock' on market exclusivity, as detailed in Figure 1 and Table 1, the industry is now entering a phase of rapid, massive-scale conversion.
B. Platform Pillars: Enzymes and Concentration
The SC market is built on "platform economics", enabling technologies that act as essential infrastructure for the entire industry. The transition from IV to SC delivery for antibody biologics is not merely a packaging change; it is a complex bioengineering challenge. The subcutaneous tissue (hypodermis) consists of a collagenous extracellular matrix filled with hyaluronic acid (hyaluronan), a glycosaminoglycan that creates a viscous, gel-like barrier to fluid flow. This physiological constraint limited SC injection volumes to 1.5-2.0 mL. Rapid injection of larger volumes into this space causes painful tissue distortion, backpressure, and leakage. To bypass these limitations and deliver 10 - 20 mL volumes required for oncology antibodies, the industry relies on two primary technological pillars: enzymatic permeation enhancement and ultra-high concentration formulation.
B1. Human hyaluronidase based Large-Volume Subcutaneous (LVSC) delivery
The dominant technology enabling Large-Volume Subcutaneous (LVSC) delivery is the use of recombinant human hyaluronidase. This enzyme temporarily depolymerizes the hyaluronan in the SC space, reducing the viscosity of the extracellular matrix and increasing the hydraulic conductivity of the tissue. This allows for the rapid dispersion and absorption of co-administered antibody biologics in volumes exceeding 10 mL, within 3 to 5 minutes. The depolymerization of the hyaluronan is repairable, with the hyaluronan barrier reconstituting within 24 to 48 hours.
The competitive landscape for this technology is currently defined by three major global players (Table 2), each leveraging unique enzymatic variants and business models as detailed in the analysis below.
Halozyme Therapeutics is the undisputed market leader with its ENHANZE® drug delivery technology. The company uses a proprietary enzyme, rHuPH20 (PH20), which is co-formulated with partner biologics. Halozyme operates on a high margin licensing model, securing royalties on the net sales of commercialized products. The company has successfully partnered with major pharmaceutical entities including Roche, Bristol Myers Squibb (BMS), J&J, and Takeda. Halozyme projected its royalty revenues to approach $1B by 2027, driven by "Wave 3" product launches such as Tecentriq SC and Opdivo SC. The ENHANZE platform is validated by regulatory approvals across the globe, solidifying its position as the standard for LVSC enablement.
Alteogen, a South Korean biotechnology firm, has emerged as the primary challenger to Halozyme’s monopoly with its ALT-B4 technology. ALT-B4 is a novel human hyaluronidase variant that Alteogen claims possesses superior thermal stability and lower immunogenicity compared to the wild-type rHuPH20. Alteogen secured a landmark exclusive agreement with Merck (MSD) to develop the SC version of Keytruda (pembrolizumab), the world's best-selling oncology drug. This partnership is strategically critical, as Keytruda SC is expected to act as a defensive bulwark for Merck against the patent expiration of the IV formulation in 2028. Additionally. In early 2025, Alteogen also signed a licensing deal with AstraZeneca for multiple oncology assets, further validating its technology stack.
Beyond Halozyme and Alteogen, Shanghai Bao Pharmaceuticals (HKEX: 2659.HK) has emerged as a key player in the LVSC enablement space. The company, which listed on the Hong Kong Stock Exchange in December 2025 with a market capitalization exceeding US$3B, focuses on enzymatic permeation enhancement to facilitate the delivery of high-dose biologics via its flagship asset KJ017 (HYSORPTASE®), a clinical-stage recombinant human hyaluronidase.
B2. Ultra-Concentration Delivery
For biologics that cannot or do not use hyaluronidase, the alternative strategy is to increase the concentration of the protein in the formulation to reduce the total injection volume to a manageable 1-3 mL. However, increasing protein concentration (often >150 mg/mL) leads to exponential increases in viscosity, known as the "crowding effect," which can make the solution impossible to inject through a fine-gauge needle. These ultra-concentration technologies are critical for the "non-enzyme" segment of the market, particularly for therapies targeting autoimmune diseases where patients self-administer medications at home using autoinjectors, and where the volume limit of 2.25 mL (standard pre-filled syringe capacity) is a hard constraint. Table 3 summarizes the key players and distinct technological approaches currently overcoming the 'crowding effect' to enable ultra-high concentration subcutaneous delivery.
Elektrofi developed the Hypercon™ technology that can achieve protein concentrations up to 500 mg/mL through microparticle-based suspensions, drastically shrinking injection volumes to enable convenient, self-administered SC formats like prefilled syringes. In late 2025, Halozyme acquired Elektrofi for $900M to integrate its Hypercon™ ultra-high-concentration platform as a complementary tool alongside ENHANZE® for large-dose SC delivery.
Lindy Biosciences overcomes the volume limitations of SC delivery using Microglassification™ technology to create stable, high-density protein microbeads that achieve concentrations >400 mg/mL. In October 2024, the company partnered with Lifecore Biomedical to scale this platform for commercial manufacturing, signaling its readiness for clinical-stage application.
UK-based Arecor uses a different method called the Arestat™ platform. Instead of using enzymes to open space in the body, they use a special mix of ingredients (called excipients) to keep proteins stable and "thin" in a liquid.
Part II.
The subcutaneous (SC) Evolution: Commercial Validation and Healthcare Economic Value
A. Commercial Mega-Blockbuster Validation
Proven performance from industry leaders demonstrates that when SC options are available, the market (patients and providers) shifts almost immediately.
In oncology, SC delivery serves as a critical driver of clinical efficiency by addressing the dual challenges of institutional capacity and patient "time toxicity". The transition of high-volume antibody biologics including Darzalex (J&J), Herceptin (Genentech), Tecentriq Hybreza (Genentech), and Opdivo Qvantig (BMS) from infusions to rapid injections allows facilities to maximize patient throughput without expanding physical infrastructure. Darzalex (J&J) Franchise sales reached $10.448B in the first 3 quarters of 2025. The SC formulation, Darzalex Faspro, is now the primary revenue driver in the U.S., transforming a 7-hour infusion into a 3-minute injection. Phesgo (Roche) achieved 54% sales growth in the first 3 quarters of 2025. Global conversion from intravenous (IV) to this SC fixed-dose combination has effectively defended the franchise against IV biosimilar competition. This evolution is supported by the dominance of fully human monoclonal antibodies; their superior safety profiles have established SC administration as the contemporary standard for both hematologic malignancies and maintenance immunotherapy.
In the immunology area, SC administration is the established benchmark for managing chronic inflammatory conditions such as rheumatoid arthritis (RA) and Crohn’s disease using low-volume/ultra-concentration technologies. While market leaders like Humira and Skyrizi (AbbVie) maintain high revenues through pre-filled syringes and self-administered autoinjectors, the sector is increasingly defined by the emergence of "bio-betters." Innovations such as Zymfentra (Celltrion), the first SC formulation of infliximab (Pfizer), represent a paradigm shift by migrating traditional IV therapies from medical to pharmacy benefits. This transition enhances patient autonomy and allows for home-based remission management, providing a strategic defense against biosimilar erosion through superior convenience.
In the neurology segment, SC delivery serves as a vital frontier for mitigating the physical and logistical burdens associated with Multiple Sclerosis (MS) and General Myasthenia Gravis (gMG). Modern formulations, such as Ocrevus Zunovo for MS treatment (Genentech), have condensed intensive, bi-annual infusions into ten-minute injections, providing a potent competitive alternative to monthly self-administered therapies like Kesimpta (Novartis). Vyvgart Hytrulo for gMG treatment (Argenx) utilizes Halozyme’s technology to deliver a large volume of Efgartigimod. The SC option is crucial for this patient population, as muscle weakness can make travel to infusion centers particularly burdensome. The approval for CIDP further broadens the SC footprint in rare neurological diseases. Vyvgart Sales nearly doubled year-over-year to $2.86B in the first 3 quarters of 2025. This momentum is further fueled by the "convenience flywheel" of at-home self-injection.
B. FDA Consideration: PK-Based Bridging and Non-Inferiority
The transition of an existing IV therapeutic to a SC format is governed by regulatory requirements designed to ensure that the new route of administration is as safe and effective as the original. The primary mechanism for this transition is the pharmacokinetic (PK)-based clinical bridging study.
A PK bridging study allows drug developers to bypass the most time-consuming and expensive stages of traditional drug development, specifically the Phase 2 (Dose-Finding) and Large-Scale Phase 3 (Efficacy) trials. Since the "active ingredient" has already been proven effective in its original IV form, regulators do not require the company to prove the drug "cures the disease" all over again. Instead of enrolling thousands of patients to measure clinical outcomes, such as tumor reduction or muscle strength improvement, the study only needs a small "pivotal" group to demonstrate that the SC version reaches the same concentrations in the bloodstream as the approved IV version.
By shifting the focus from clinical efficacy to pharmacokinetic metrics, the bridging pathway significantly reduces development duration and complexity, as shown in Table 4.
Because the clinical efficacy is already established, the focus shifts entirely to Safety and Pharmacokinetics. While traditional efficacy trials are skipped, the developer must still conduct abbreviated trials to monitor for injection-site reactions and immunogenicity (ensuring the body doesn't develop a new immune response to the skin-based delivery). By utilizing mathematical metrics like C-trough and AUC to prove "non-inferiority," a transition that would normally take five to seven years can be compressed into a fraction of that time. This allows a manufacturer to bring a more efficient delivery method to market using existing data as the foundation. For example, Darzalex Faspro, the COLUMBA trial served as the pivotal study, demonstrating that the SC formulation was non-inferior to the IV version in terms of overall response rate and trough concentrations, while also providing a superior safety profile regarding infusion-related reactions (IRRs).
C. Healthcare Economic Value
The economic case for SC biologics is a study in contrasts. It offers unambiguous efficiency savings for healthcare systems and quality-of-life improvements for patients, but it presents a financial challenge for providers in fee-for-service models.
Workflow & Pharmacy Efficiency Rigorous "Time and Motion" studies have quantified the operational benefits of SC administration. These metrics are the primary selling point for hospital administrators and payers. SC formulations streamline the technical labor of medication management by eliminating the complexities of the IV compounding process. Because these products are fixed-dose and ready-to-use, they require no reconstitution or weight-based dilution, which reduced pharmacy preparation time for Phesgo by 78.2 minutes. This simplified workflow minimizes the risk of compounding errors and allows the pharmacy to respond more dynamically to patient arrivals. By removing the need for labor-intensive admixture, healthcare systems can optimize pharmacy staff allocation and significantly reduce the "prep-to-bedside" lag time common in traditional oncology and immunology clinics.
Operational Capacity & Throughput The shift from IV to SC administration significantly expands facility capacity by reclaiming "chair time" and increasing patient turnover. Data from the ADEPT trial sub-study reveals that Phesgo SC reduces patient chair time from 84.3 minutes to 22.5 minutes. The impact is even more dramatic for Darzalex, where SC administration achieves a 97% reduction in chair time (from a median 7-hour infusion to only minutes). For hospital administrators, these metrics represent a direct increase in throughput, allowing more patients to be treated per day without the capital expense of adding more infusion chairs or physical space.
D. System-Wide Cost Savings
From a payer and health system perspective, SC antibody biologics offer direct cost advantages on waste elimination and system-wide savings.
Wastage Elimination IV drugs dosed by body weight (mg/kg) often result in "vial wastage" where the remainder of a single-use vial is discarded. Fixed-dose SC formulations eliminate this wastage entirely. Studies indicate potential savings of 93% to 100% in wastage costs, translating to thousands of Euros/Dollars per patient over a full treatment course.
System-Wide Savings A systematic review estimated that transitioning to SC trastuzumab/pertuzumab could save the US healthcare system ~$10,138 per patient in administration-related costs.
Part III.
The Future Outlook: "Bio-Betters" and Next-Gen Modalities
A. The Era of Subcutaneous (SC) Dominance (2025-2035)
The growth runway for SC therapeutics extends well into the next decade as the technology evolves from a lifecycle tactic into a true clinical advancement. As the market matures toward 2035, the strategic focus will shift from "proof of concept" to widespread "standard of care" adoption.
A1. The "Next Wave" of Mega-Blockbusters
The immediate future of the oncology market, spanning 2025 to 2028, is being defined by a massive strategic pivot toward SC formulations in the PD-1/PD-L1 inhibitor products. This transition is headlined by the launch of Keytruda Qlex (pembrolizumab and berahyaluronidase alfa), which utilizes Alteogen’s hyaluronidase technology to deliver a treatment that previously required a lengthy infusion in just one to two minutes. With Keytruda currently generating over $30B in annual revenue and accounting for nearly half of Merck’s total earnings, this SC rollout is a defensive maneuver of unprecedented scale. By aiming to convert 30% to 40% of its market share to the SC version before the 2028 patent expiration of the intravenous (IV) molecule, Merck is attempting to secure its franchise dominance and cushion the financial impact of the impending "patent cliff."
Bristol Myers Squibb (BMS) is executing a similarly aggressive lifecycle management strategy with the launch of Opdivo Qvantig (nivolumab and hyaluronidase-nvhy). As the first SC PD-1 inhibitor approved in major markets in the EU, Opdivo SC is designed to transform a multi-billion-dollar revenue stream by shifting a significant portion of its $10B IV injectable franchise to the more convenient injection format. BMS has explicitly targeted a conversion rate of 30% to 40% of its U.S. volume to the SC formulation, emphasizing benefits of a 3- to 5-minute administration time and reduced burden on infusion center capacity. These strategic shifts by both Merck and BMS represent a broader industry trend where the "backbone" therapies of modern oncology are being re-engineered to maintain market exclusivity and patient loyalty well into the next decade.
A2. The Rise of “Bio-Betters”
By 2030, the "originator monopoly" on SC formulations is expected to fracture as the industry moves toward Bio-betters, such as Celltrion’s Zymfentra. As the first SC formulation of infliximab, Zymfentra proves that biosimilar developers now possess the technical capability to innovate beyond simple replication, offering superior convenience through at-home care. This shift effectively moves the competitive landscape from traditional medical benefits toward more accessible pharmacy benefits, allowing these products to compete directly with originators on clinical delivery and patient lifestyle rather than just price.
As patents on hyaluronidase delivery technologies expire or are circumvented, and high-concentration formulation IP becomes more accessible, a wave of "SC Biosimilars" will emerge to challenge established market shares. These next-generation products will not only match the efficacy of originators but will also prioritize launch timing and patient-centric benefits. This evolution signifies a broader trend where technical expertise in SC delivery becomes the primary battleground, forcing originators to defend their power against more agile competitors who can offer the same therapeutic outcomes in a more convenient, localized format.
B. Next-gen Modalities
The SC revolution is expanding beyond monoclonal antibodies into more complex modalities like bispecific antibodies and antibody-drug conjugates (ADCs). For bispecifics, SC delivery is a strategic shift that can mitigate intense systemic side effects, such as cytokine release syndrome, by providing a slower, controlled absorption through the lymphatic system. This improves the safety profile and reduces the need for prolonged inpatient monitoring while maintaining therapeutic efficacy.
In the realm of ADCs, SC platforms address the pharmacokinetic challenges of delivering highly potent, toxic payloads. Utilizing technologies like hyaluronidase to facilitate volume absorption allows for more flexible dosing and shifts care from the clinic to the home. By streamlining administration for these multi-functional molecules, the SC platform is establishing itself as the essential foundation for the next generation of patient-centric oncology and immunology biologics.
C. Regional Market Dynamics
The global adoption of SC antibody biologics is not uniform. It is shaped by regional healthcare infrastructure, reimbursement policies, and the strategic priorities of local pharmaceutical champions.
By the end of 2024, North America maintains a dominant share of the global SC revenue (45–50%), a position underpinned by high reimbursement rates for biologics and the rapid clinical uptake of premium-priced formulations like Phesgo and Darzalex Faspro. The region's market dynamics are further complicated by the Inflation Reduction Act (IRA); while the legislation aims to negotiate prices for high-spend drugs, switching to an SC "new formulation" can effectively reset negotiation timelines or differentiate a product sufficiently to maintain favorable formulary status.
Asia-Pacific innovators like Alteogen and Celltrion are no longer just followers; they are directly challenging Western monopolies. In contrast to traditional Western dominance, the Asia-Pacific region has emerged as the industry's primary innovation hub and growth engine, with South Korea establishing itself as the global epicenter for SC delivery technology. Asia-Pacific is unequivocally the fastest-growing region, projected to exhibit the highest CAGR through 2035. Home to primary challengers like Alteogen and biosimilar leaders like Celltrion, this concentration of technical expertise is driving a wave of licensing deals that rivals traditional Western hubs, particularly in markets like China where SC efficiency helps bypass critical hospital infusion bottlenecks.
Meanwhile, Europe serves as the primary biosimilar battleground, characterized by a unique tension between originators and developers. While originators historically used patent-protected SC reformulations to "evergreen" their products and prevent switching to cheap IV biosimilars, the entry of "Bio-betters" and SC biosimilars is now challenging this defense strategy on its own turf, forcing a shift in how market share is retained in tender-based systems.
Part IV.
Conclusion
The SC biologics market has entered a Golden Age, evolving from a niche tactic into a mandatory commercial playbook for the world's largest drug franchises. Driven by the convergence of high-concentration science and validated enzyme platforms, this shift is the primary defense for big pharma against the impending "patent cliff." For investors, this represents a massive opportunity as the biologics sector scales toward a US$1T valuation by 2035.
The oncology sector has reached a critical inflection point, with the recent approvals of Opdivo Qvantig and Keytruda Qlex validating SC delivery for the industry’s highest-revenue anchors. By slashing administration from hour-long infusions to 2-minute injections, these products create a commercial flywheel that will define Biopharma profitability for the next decade. This mechanism simultaneously increases clinic throughput, improves patient adherence, and protects flagship assets from biosimilar competition.
Ultimately, the next decade will witness the largest migration of antibody biologics revenue from IV to SC in history. This transition reshapes the entire value chain, from delivery-tech providers like Halozyme and Alteogen to global originators. Investors are looking at a decade-long runway of high-margin growth as the industry systematically re-engineers how complex medicine is delivered and financed.
Acknowledgement
We would like to express our deepest gratitude to the dedicated team at Tribridge BioCapital for their collaborative spirit and technical rigor in bringing this report to fruition.
Core Research and Authorship
Dr. Hua Xu (Ph.D. in Physiology from the University of Arizona): A veteran in biomedical research who spearheaded the scientific foundation and clinical data strategy for this analysis. Through rigorous oversight, Dr. Xu ensured the report’s accuracy.
Dr. Sherry Ying Li (Ph.D. in Molecular Biology from Yale University): A former researcher at Bristol Myers Squibb (BMS) and Roche. She led the analysis of oncology and immunology market dynamics, providing the expert framework for the report's clinical data and strategic market insights. Through rigorous oversight, Dr. Li ensured the report’s accuracy.
Kai Zhao: A technical specialist with a background in advanced biotechnology and data synthesis, Kai was instrumental in the construction of Tribridge BioCapital knowledge base.
Henry Qiu: As the lead for AI-assisted workflows, Henry constructed the internal Knowledge Base and established Prompt Engineering SOPs for the subject matter experts.
Hesen Huang: As one of research analysts who received M.S. in Applied Mathematics from Northeastern University, Hesen is responsible for following tasks: Report Embellishment; Data Analysis and Visualization; AI-assisted Research & Review.
Mengdie Zhao: A contributor with a Master’s degree from Georgetown University, Mengdie supported market research and competitive landscape analysis.
Alyssa Li: A financial analyst with a Master’s degree in Economics from Northeastern University, specializing in financial modeling and investor relations. Alyssa served as a content advisor for this analysis, overseeing the selection of market-critical data.