The Battle for IL-17A Therapeutics: How Domestic Players Are Breaking Import Monopolies

The IL-17A Targeted Therapy Market Enters an Era of Fierce Competition—Hengrui Pharma’s Funakizumab Gains Approval for a New Indication, Becoming Another Sharp Weapon for Domestic Drugs in the Field of Ankylosing Spondylitis. Among the five IL-17A monoclonal antibodies already marketed in China, imported drugs hold three positions, but domestic counterparts represented by GENRIX BIO, Hengrui Pharma, and Junshi Biosciences are launching a counteroffensive with higher affinity and superior clinical data. From psoriasis to ankylosing spondylitis, and from imitation to innovation, this battle of targeted therapies is not only a contest of technical prowess but also a life-or-death race for market positioning. As IL-17A biosimilars flood into Phase III clinical trials, can domestic drugs break through the encirclement amidst intense “involution”?

In the field of autoimmune disease treatment, IL-17A-targeted therapies have become an important therapeutic approach. Currently, five IL-17A monoclonal antibodies have been approved in China, forming a competitive landscape characterized by three imported drugs and two domestically produced ones. These five agents are secukinumab (Novartis), ixekizumab (Eli Lilly), and bimekizumab (UCB) as the imported products, along with sesukimab (GENRIX BIO) and funakizumab (Hengrui Pharma) as the domestically produced options. Notably, bimekizumab potently and selectively neutralizes both IL-17A and IL-17F, whereas the other four agents target only IL-17A.

In this fiercely competitive market, domestic pharmaceutical companies such as GENRIX BIO, Hengrui Pharma, and Junshi Biosciences are leveraging ultra-high-affinity antibodies as a strategic approach to break the monopoly held by imported drugs. Taking Hengrui Pharma’s funakizumab as an example, this recombinant humanized IgG1 subtype monoclonal antibody against IL-17A retains only 0.8% murine-derived components, thereby enhancing affinity for IL-17A while reducing immunogenicity. Compared with the already approved secukinumab and ixekizumab, funakizumab demonstrates higher affinity for IL-17A and a stronger capacity to block the IL-17A/IL-17R interaction, conferring potential advantages in therapeutic efficacy.

Among the breakthrough contenders in the domestic IL-17A targeted therapy landscape, GENRIX BIO’s secukinumab biosimilar (Sailiqimab) is also a force to be reckoned with. As the first domestically approved IL-17A monoclonal antibody, Sailiqimab has adopted a differentiated technical pathway—achieving low immunogenicity through fully humanized design and enhancing antibody stability via high-density glycosylation modification technology. Unlike Hengrui Pharma’s funakizumab, GENRIX BIO has entered the market with a strategy focused on “pricing + differentiation in indications.” Sailiqimab is priced 30%–40% lower than imported drugs and has rapidly captured the grassroots market by prioritizing the psoriasis indication. Furthermore, Sailiqimab received approval in January for the treatment of ankylosing spondylitis (radiographic axial spondyloarthritis), and its application of the IL-17A target in lupus nephritis is currently under exploration.

However, the challenges facing selicrelimab are equally evident. On one hand, its technological highlights are centered on glycosylation modification, and its clinical differentiation advantages have not yet been fully demonstrated; on the other hand, facing catch-up competition from latecomers such as Hengrui Pharma and Junshi Biosciences, GENRIX BIO needs to implement a combination strategy in commercialization efficiency and national reimbursement drug list (NRDL) access.

As flagship products of major international pharmaceutical companies, secukinumab and ixekizumab have established a solid market foundation. Since its approval in 2014, secukinumab has been widely used in numerous countries and regions worldwide, covering multiple indications including psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and pustular psoriasis. In 2023, the drug’s global sales reached $4.98 billion, with first-half 2024 global sales amounting to $2.852 billion, representing a 23% year-on-year increase, which underscores its significant market influence. Ixekizumab has also demonstrated strong performance, achieving impressive sales of $2.76 billion in 2023. Leveraging their first-mover advantage, both drugs have garnered high levels of recognition and trust among physicians and patients.

However, imported drugs are not invulnerable. With the rise of domestically produced pharmaceuticals in China, imported drugs face numerous challenges. In terms of pricing, Chinese-made drugs may have a cost-control advantage, allowing them to enter the market at more affordable prices and thereby disrupting the pricing structure of imported drugs. Regarding distribution channels, domestic pharmaceutical companies possess a deeper understanding of the Chinese market, enabling them to develop precise marketing strategies tailored to the needs and characteristics of local patients, thus offering greater flexibility in channel expansion. Furthermore, in terms of product attributes, the high-affinity advantage of certain domestic drugs, such as funakizumab, may attract increasing attention from both patients and physicians, gradually capturing market share from imported drugs.

Hengrui Pharma’s funakizumab has drawn significant attention for its performance in the treatment of ankylosing spondylitis. In its Phase III clinical trial evaluating the treatment of active ankylosing spondylitis, funakizumab demonstrated excellent efficacy data. At Week 16, the ASAS20 response rate in the 120 mg group reached 65.6%, the ASAS40 response rate was 46.3%, and the ASAS5/6 response rate was 55.4%. These figures were all significantly superior to those observed in the placebo group, with therapeutic benefits continuing to improve through Week 32. As early as Week 2, the ASAS20 response rate in the funakizumab 120 mg group had already surpassed that of the placebo group, reaching 34.0%. Meanwhile, substantial improvements were also seen compared to placebo in total back pain VAS scores, morning stiffness, and inflammatory markers.

These impressive data are underpinned by robust technological support. As a recombinant humanized IgG1 subtype monoclonal antibody targeting IL-17A, funakizumab retains only 0.8% murine-derived components. This unique design enhances its affinity for IL-17A while effectively reducing immunogenicity. Compared with the approved agents secukinumab and ixekizumab, funakizumab demonstrates higher affinity for IL-17A, enabling more effective blockade of the IL-17A/IL-17R signaling pathway, thereby suppressing inflammatory responses and alleviating symptoms in patients with ankylosing spondylitis.

From psoriasis to ankylosing spondylitis, Hengrui Pharma has taken significant steps in its multi-indication layout for IL-17A targeted therapies. This strategy bears similarities to the “Keytruda myth.” Since its launch in 2014, Keytruda (pembrolizumab) has gained approval for 40 indications worldwide, thanks to its remarkable efficacy in treating various types of cancer, becoming a representative drug in the field of tumor immunotherapy. Its sales reached as high as $29.4 billion in 2024. By expanding the indications for funakizumab, Hengrui aims to achieve similar market influence and clinical value.

In the field of psoriasis treatment, funalikizumab has been approved for adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, providing a new therapeutic option and breaking the long-standing monopoly held by similar imported drugs. The recent breakthrough in the indication for ankylosing spondylitis has further enriched its product portfolio. In the future, funalikizumab will also undergo Phase III clinical studies for psoriatic arthritis and moderate-to-severe chronic plaque psoriasis in children and adolescents. If these studies prove successful, funalikizumab will cover a broader range of autoimmune diseases, forming a comprehensive treatment system. This will not only benefit more patients but also secure greater competitive advantages for Hengrui Pharma in the IL-17A targeted therapy market, enhancing its brand influence and market share, and writing its own “legend” in the field of autoimmune disease treatment.

The Development History of IL-17A Monoclonal Antibodies: A Fascinating Chronicle of Technological Evolution, Marked by Three Generations of Advancements, Each Building on Its Predecessor with Breakthrough Innovations and Enhanced Performance.

First-generation IL-17A monoclonal antibodies are represented by secukinumab, which selectively blocks IL-17A. As the world’s first fully human IL-17A inhibitor, the development of secukinumab marked a significant advancement in antibody technology. The emergence of Medarex mice in 1999 made it possible to produce fully human antibodies using transgenic mice. In 2001, researchers injected human IL-17A into these transgenic mice, isolated B cells capable of producing human antibodies from the immunized mice, and then employed classical hybridoma technology to screen for hybridomas that produced specific antibodies. Following isolation and purification, secukinumab was successfully developed.

This fully humanized design demonstrates low immunogenicity and a favorable safety profile in clinical applications. In the CLEAR study on psoriasis treatment, secukinumab achieved the highest PASI response rates when used early in biologic-naïve patients. The PURE registry study also indicated that early use of secukinumab resulted in higher skin clearance rates. Regarding the treatment of ankylosing spondylitis, the MEASURE study series demonstrated that secukinumab alleviated back pain within one week, morning stiffness and fatigue within four weeks, and rapidly and significantly reduced disease activity by 16 weeks. The therapeutic efficacy was sustained for four years, and in extension studies, nearly 80% of patients experienced sustained relief of symptoms and signs over five years of treatment.

Bimekizumab, a representative second-generation IL-17A monoclonal antibody, achieves dual-target inhibition of IL-17A and IL-17F. By selectively binding to human IL-17A, IL-17F, and the heterodimer IL-17A/F cytokines, bimekizumab inhibits their interaction with the IL-17 receptor complex, thereby blocking inflammatory responses. In the pivotal Phase III BEMOBILE trial for axial spondyloarthritis, bimekizumab demonstrated significant efficacy, with marked relief in pain and morning stiffness observed within one week of the first dose. After 16 weeks, nearly half of the patients achieved significant disease remission criteria, and this proportion increased to approximately 60% at 52 weeks. MAIC studies (indirect comparisons) have shown that bimekizumab offers superior efficacy compared to existing commonly used biologic therapies for patients with ankylosing spondylitis. Inflammatory markers were significantly reduced within two weeks of treatment, and inflammation levels decreased by approximately 60% after 16 weeks. Furthermore, it significantly improves spinal inflammation and structural damage, holding promise for further controlling disease progression.

A representative third-generation IL-17A monoclonal antibody is funakizumab, which is characterized by ultra-high affinity and low immunogenicity. Funakizumab is a recombinant humanized IgG1 anti-IL-17A monoclonal antibody independently developed by Hengrui Pharma, retaining only 0.8% murine-derived components. This unique design enhances its affinity for IL-17A while reducing immunogenicity.

In the race to develop IL-17A-targeted therapies, competition among biosimilars has become intensely fierce. Taking secukinumab biosimilars as an example, multiple candidates, including Bio-Thera Solutions’ BAT2306 and CSPC Pharmaceutical Group’s CMAB015, have entered Phase III clinical trials. BAT2306 has advanced rapidly, completing global Phase III clinical studies, with market launch anticipated as early as 2025. On December 17, 2024, Bio-Thera Solutions signed a licensing, manufacturing, supply, and commercialization agreement with Stein, granting Stein exclusive rights to commercialize BAT2306 in Brazil and other Latin American markets. This transaction includes a $1.2 million upfront payment, cumulative milestone payments of up to $6.8 million, and double-digit percentage royalties on net sales, underscoring Bio-Thera’s proactive expansion in its biosimilar portfolio.

As more companies flock into this biosimilar track, competition intensifies continuously, and profit margins are severely squeezed. On one hand, high R&D costs are a factor that cannot be ignored. Although the development of biosimilars may involve shorter cycles and lower costs compared to innovative drugs, substantial capital investment is still required for clinical trials, optimization of manufacturing processes, and other aspects. Taking Bio-Thera Solutions as an example, its total investment in six Phase III clinical projects in 2023 reached RMB 415.1925 million, accounting for 65.54% of the company’s total annual R&D expenditure, with BAT2306 (secukinumab) alone consuming RMB 128.8377 million. On the other hand, market competition pressures constrain product pricing. As numerous biosimilars enter the market, price wars become almost inevitable in the race for market share. The originator drug secukinumab has already secured a certain market share in China, and with the rise of domestically produced innovative drugs, market competition has become more diversified. It is not easy for biosimilars to gain a price advantage, which further compresses profit margins.

The development trajectories of innovative drugs and biosimilars targeting the same molecule present a stark contrast. Innovative drugs, such as Hengrui Pharma’s funakizumab, command higher pricing and profit margins in the market by leveraging their unique technological advantages and innovative design concepts. In contrast, biosimilars, being essentially copies of originator biologics, face significant challenges in product differentiation and are largely confined to competing on price and cost. The implementation of medical insurance cost-containment measures and centralized volume-based procurement (VBP) policies has further exerted substantial downward pressure on biosimilar prices, thereby squeezing their profit margins. In this competitive landscape, biosimilar manufacturers must continuously optimize production processes and reduce costs while ensuring product quality, alongside strengthening marketing efforts and channel development, to secure a share of the market.

In the future pharmaceutical market, IL-17A-targeted therapies will face new challenges and opportunities, with the potential to break through in three key areas and open up broader avenues for development.

In terms of indication expansion, IL-17A targeted therapies are currently primarily used for autoimmune diseases, such as psoriasis and ankylosing spondylitis. However, with advancing research, they have demonstrated significant potential in the treatment of rare diseases. Taking hidradenitis suppurativa as an example, this is a relatively rare chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses, and sinus tracts, which severely impair patients' quality of life. Novartis’s secukinumab has made progress in the treatment of hidradenitis suppurativa and has received marketing approval from the European Commission. Research into IL-17A targeted therapies for other rare diseases, such as lupus nephritis and thyroid eye disease, is also steadily advancing; GENRIX BIO’s sarilumab biosimilar (Sai Li Qi Dan Kang) has entered Phase II clinical trials.

For lupus nephritis, current treatment options are limited. The introduction of IL-17A-targeted therapies may provide patients with new treatment choices, potentially improving renal function and slowing disease progression. In thyroid eye disease, blocking the IL-17A signaling pathway could alleviate ocular inflammation and relieve symptoms such as exophthalmos and diplopia. Achieving breakthroughs in these rare disease areas would allow IL-17A-targeted drugs to fill gaps in clinical treatment, bringing hope to more patients while also expanding their market potential and enhancing product value.

The revolution in drug administration routes is also a key direction for the future development of IL-17A-targeted therapies. Currently, IL-17A monoclonal antibodies are primarily available as injectable formulations. Whether administered via subcutaneous or intravenous injection, they pose significant inconveniences to patients. Frequent injections not only increase patient discomfort but may also trigger local adverse reactions at the injection site, such as redness, swelling, pain, and infection, thereby causing considerable disruption to patients’ daily lives and work.

The development of oral IL-17A-targeted therapies has become a key objective for numerous pharmaceutical companies. Oral formulations offer significant advantages, including ease of use and improved patient adherence, as patients can self-administer medication in their daily lives without frequent visits to hospitals or clinics for injections, thereby greatly enhancing treatment convenience and continuity. Currently, several pharmaceutical companies have made progress in the development of oral IL-17A modulators. For instance, Denmark’s LEO Pharma has achieved results in the discovery process of an oral PPI modulator targeting IL-17A (cpd23). However, the development of oral formulations faces many challenges, such as drug stability, bioavailability, and gastrointestinal absorption. As a protein, IL-17A is prone to degradation in the gastrointestinal environment; therefore, ensuring its stability and effective absorption within the gastrointestinal tract is a critical hurdle in developing oral formulations. If these technical challenges can be successfully overcome, oral IL-17A-targeted therapies will disrupt the current injection-dominated landscape and emerge as new market favorites.

In the global competitive landscape, Chinese-made IL-17A targeted therapies face significant challenges from the patent cliff as they expand overseas. Taking Novartis’s secukinumab as an example, its core patent in China was granted in 2012 and is set to expire in 2025, while the patent protection for ixekizumab will also expire in 2026. Following these expirations, a surge of biosimilars will enter the market, intensifying competition. To establish a foothold in the international market, Chinese pharmaceutical companies must adopt effective strategies to navigate the patent cliff. On one hand, companies can strengthen independent R&D by leveraging innovative technologies and unique designs to develop differentiated products, thereby avoiding patent conflicts with originator drugs. On the other hand, active international cooperation serves as a crucial pathway. Companies can collaborate with foreign research institutions and pharmaceutical firms to jointly conduct clinical trials and share R&D outcomes, utilizing partners’ resources and distribution channels to accelerate product internationalization. Additionally, mechanisms such as cross-licensing agreements can facilitate cooperation with originator companies, enabling entry into the international market within a legal framework. This approach will enhance the global competitiveness of Chinese-made drugs and achieve a strategic leap from domestic to international markets.

Confronted with the market monopoly of imported drugs and the fierce competition from biosimilars, the true test may only just be beginning. As the advantage in clinical data needs to translate into physicians’ prescribing habits, and as technological breakthroughs encounter price suppression during national reimbursement negotiations, the breakout of domestically produced drugs is destined to be a protracted struggle. In the future, whoever first masters oral formulations and secures global indications will occupy the high ground in the “red ocean” of IL-17A targets. The endgame of this battle may well redefine the value coordinate system for China’s innovative pharmaceuticals.