Boston Scientific and Hengrui Medical Forge Ahead in the Oncology Interventional Market through Pharma-Device Integration

Boston Scientific and Hengrui Medicine are leaders in the global medical device and pharmaceutical sectors, respectively, with keen insights into global trends in oncology therapies. In recent years, the tumor embolization microsphere sector has garnered simultaneous favor from both of these industry giants.

In 2019, Boston Scientific completed its $4.2 billion acquisition of BTG, a company specializing in interventional medicine, and launched drug-eluting small-particle microspheres in the Chinese market; Hengrui Medicine introduced Callisphere polyvinyl alcohol embolic microspheres, with this single product generating over RMB 600 million in revenue in 2019.

Leading companies bullish on tumor embolization microspheres include not only Boston Scientific and Hengrui Medicine. In 2018, CDH Investments partnered with Grand Pharma to acquire Sirtex, an Australian manufacturer of microspheres for interventional vascular therapy of liver cancer, for AUD 1.9 billion. In 2019, Varian acquired Hangzhou Alicon Pharmaceutical Technology (Alicon), a company specializing in embolization therapy. Keruichi, a domestic developer of interventional embolization microspheres, completed a C-round financing worth hundreds of millions of RMB in December 2020, co-led by Hillhouse Capital and Yusheng Venture.

What Makes Tumor Embolization Microspheres So Appealing That Pharmaceutical and Medical Device Giants Keep Betting on Them?

Tumor interventional embolization therapy is one of the three major subfields of interventional oncology, with the other two being ablation therapy and radiation therapy. As a drug-device combination product, interventional embolization microspheres face high R&D barriers, resulting in limited market participation. Meanwhile, unmet therapeutic needs persist across major global markets, making it a blue-ocean market.

How Does Interventional Embolization Therapy "Strangle" Tumors? Who Are the Players in This Blue-Ocean Market? What Will Be the Key Growth Drivers for the Future Tumor Interventional Therapy Market? VCBeat (WeChat ID: vcbeat) has compiled an overview of this field.

The principle of interventional embolization therapy for tumors is rather “aggressive”: it involves occluding the tumor’s blood-supplying vessels with embolic materials, thereby inducing ischemic necrosis of the tumor tissue. In the treatment of primary liver cancer, interventional embolization therapy holds an unshakable position. Beyond simply “blocking off the tumor,” drug-eluting embolic microspheres can be loaded with anticancer agents or combined with drug-conjugated microparticles or microspheres to achieve chemoembolization, thereby delivering a “dual-pronged” therapeutic effect.

Transarterial Chemoembolization (TACE) is the preferred first-line treatment for intermediate- to advanced-stage hepatocellular carcinoma. Since its inception 30 years ago, the technique has been continuously refined and improved, achieving widespread application globally.

During TACE, after inserting a microcatheter into the target feeding artery of the tumor, the physician injects an appropriate amount of embolic agent at a controlled rate to occlude the target artery, thereby inducing ischemic necrosis of the tumor tissue.

TACE technology has undergone more than 30 years of development, evolving into① Conventional Transarterial Chemoembolization (c-TACE); ② Drug-Eluting Bead Transarterial Chemoembolization (D-TACE); ③ Transarterial Radioembolization (TARE) — the three major techniques.

c-TACEConventional transcatheter arterial embolization primarily employs embolic agents such as ultra-liquefied iodized oil, gelatin sponge particles, polyvinyl alcohol (PVA) particles, and blank microspheres. Typically, one or more cytotoxic drugs (including doxorubicin and epirubicin) are mixed with iodized oil, followed by occlusion of the tumor-feeding arteries using embolic agents. The therapeutic mechanism mainly involves blocking the blood supply to the tumor, thereby inducing ischemic necrosis.

c-TACE was discovered by Professor Yamada of Japan during over a decade of hepatic angiography and chemotherapy infusion for liver cancer. He observed that angiography and chemotherapy infusion occasionally caused accidental embolization of the hepatic artery, leading to interruption or reduction of tumor blood supply, followed by tumor necrosis and shrinkage, without any complications or adverse reactions in patients.

Since its invention in 1978, c-TACE has been in use for over 40 years, yet this therapy still suffers from numerous shortcomings.

During c-TACE treatment, lipiodol must be emulsified for embolization. When gelatin sponge particles or PVA particles are used as embolic agents, precise embolization cannot be achieved. Furthermore, due to inter-operator variability, c-TACE exhibits poor reproducibility and high variability, resulting in heterogeneous and unquantifiable embolization. With the application of blank microspheres as a new generation of embolic materials, precise embolization of target vessels can be realized, thereby achieving precision and uniformity in c-TACE.

Just as coronary stents have evolved from bare-metal stents to drug-eluting stents, the field of TACE has seen the emergence of drug-eluting bead embolization (D-TACE) alongside conventional TACE (c-TACE).

D-TACEThe most significant difference from conventional c-TACE lies in the embolic agents used. D-TACE utilizes drug-eluting microspheres capable of adsorbing and carrying chemotherapeutic drugs. Unlike c-TACE, D-TACE exerts a dual mechanism in eradicating cancer cells: it not only embolizes the hepatic arteries supplying the tumor but also enables high-concentration, targeted delivery of chemotherapy directly into the tumor for an extended duration, thereby achieving a synergistic clinical effect greater than the sum of its parts (1+1>2).

Che Haibo, founder of KeraChi, explained to VCBeat: “We can simply understand D-TACE as the precise delivery of chemotherapy drugs to the vicinity of tumors using drug-eluting microspheres, thereby achieving precise local administration. The drugs exert a sustained and prolonged effect on the tumor through controlled release. Due to the long-acting, slow-release properties of drug-eluting microspheres, systemic blood drug concentrations remain low, resulting in reduced toxic side effects and greater patient benefit. This is also a concrete manifestation of the trend toward precision targeted therapy in oncology.”

From a health economics perspective, D-TACE can also reduce the financial burden on patients. Due to the high rates of recurrence and metastasis in liver cancer, patients undergoing c-TACE require an average of 3–4 treatment sessions over their course of therapy, with each session costing approximately RMB 25,000. Although D-TACE costs around RMB 45,000 per session, it is associated with fewer adverse effects, better tolerability, and greater precision. Consequently, fewer treatments are needed compared to c-TACE, with an average of only 1–2 sessions required.

However, the limited variety of drugs currently available for D-TACE necessitates the development of broad-spectrum drug-eluting microspheres for other conditions beyond liver cancer, such as lung cancer.

In recent years, a third type has also emerged in the field of TACETransarterial Radioembolization (TARE). D-TACE delivers precise chemotherapy near the tumor, while TARE delivers precise radiotherapy near the tumor.

Similar to TACE, TARE is administered via catheter through the hepatic artery. However, the interventional material used in TARE consists of microspheres embedded with radioactive isotopes. The implantation procedure mirrors that of D-TACE; once the radioactive microspheres are precisely delivered to the vicinity of the tumor, they emit short-range, high-dose beta radiation to destroy tumor cells. Nevertheless, as the radiation source in TARE comprises radioactive particles with a specific half-life, it imposes stringent requirements on facility construction, transportation, storage, and surgical procedures. Currently, no TARE products have been approved for market entry in China.

Boston Scientific has launched TheraSphere Y-90 radioactive microspheres in this field, while Grand Pharma offers SIR-Spheres Yttrium [90Y] resin microspheres, acquired from Sirtex.

Tumor treatment modalities are diverse; what is the potential market size for TACE?

Liver cancer, the primary indication for TACE, is a major global health burden. According to estimates from the American Cancer Society, more than 800,000 people worldwide are diagnosed with liver cancer each year. TACE is a cornerstone technique in the treatment of liver cancer. According to Data Bridge Market Research, the market size for embolic microspheres used in TACE is projected to reach $3.40456 billion by 2028, while the overall market for TACE applications is expected to exceed $10 billion.

Currently, the domestic TACE market is characterized by high growth, high barriers to entry, and few participants.

The high growth is primarily driven by the large base of liver cancer patients in China. Transarterial chemoembolization (TACE) is a core treatment modality for liver cancer. China accounts for approximately half of the global liver cancer patient population, with its incidence rate representing about 45% of the global total. The “Standard for Diagnosis and Treatment of Primary Liver Cancer (2019 Edition)” issued by the National Health Commission recommends TACE for liver cancer indications ranging from stage Ib to stage IIIb, covering a substantial proportion of cases.

However, the efficacy of mainstream treatment methods currently available in China is limited, and the number of therapeutic options is also fewer than that in developed countries.

High barriers to entry are primarily reflected in R&D. As a drug-device combination product, TACE products present significant challenges in both research and manufacturing, involving complex material synthesis technologies and chemical reaction systems. Industrial-scale production requires interdisciplinary R&D capabilities integrating pharmaceuticals and medical devices.

In particular, for drug-eluting microspheres used in D-TACE, a balance between rigidity and elasticity is required in terms of physical properties. The microspheres are implanted via injection through a microcatheter. During injection, the microspheres are delivered to the lesion site in a compressed state; upon reaching the target area, they must rapidly rebound to their spherical shape, allowing close packing between individual microspheres to effectively occlude the pathological blood vessels.

In addition to stringent physical property requirements, ideal drug-loaded microspheres should exhibit rapid drug loading and stable sustained release. The sustained, slow-release profile of these microspheres over an extended period is essential to effectively reduce systemic blood drug concentrations and minimize toxic side effects.

The high entry barriers in the drug-loaded microsphere industry have also resulted in a limited number of market participants. Few companies have mastered the industrialization technology for drug-loaded microspheres.

In traditional c-TACE, companies with commercialized products in China include Hangzhou Alicon Pharmaceutical Technology (Alicon), Hengrui Medicine, and Merit Medical.

Alicon has been acquired by Varian, and its polyvinyl alcohol (PVA) particle embolic agents and gelatin sponge particle embolic agents were both launched in the Chinese market in 2006. Hengrui Medicine and Merit Medical offer blank PVA microspheres.

In the field of D-TACE, the major players in China include Hengrui Medicine, Boston Scientific, Merit Medical, and Claret Medical.

Hengrui Medicine’s interventional embolization microspheres are primarily developed by its subsidiary, Suzhou Hengrui Jialisheng. Its D-TACE product is mainly the CalliSpheres® Drug-Eluting Embolic Microspheres, which are indicated for embolization therapy of hypervascular solid organ malignancies.

Boston Scientific’s D-TACE was acquired from BTG. Its core product is the Drug Delivery Embolisation System, which was launched in China in 2019 for embolization of feeding vessels in hypervascular malignant tumors.

Merit Medical, founded in 1987 and headquartered in South Jordan, Utah, has HepaSphere Microspheres as its drug-eluting microsphere product for interventional embolization listed in China.

Founded in late 2015, CareRay specializes in vascular interventional medical devices and has secured hundreds of millions of yuan in investment from institutions such as Hillhouse Capital, Yuansheng Venture Capital, and LYFE. In the field of drug-eluting microspheres, CareRay has developed DiaSphere® drug-eluting microspheres. In terms of physical properties, their strength and elasticity surpass those of existing marketed products. Regarding drug-loading performance, they enable rapid loading of multiple drugs, exhibit high drug adsorption capacity, and ensure stable drug release concentrations. Laboratory data demonstrate superior drug absorption and release rates compared to similar products. This facilitates sustained drug release at tumor sites, achieving precise chemotherapy.

VCBeat has learned that Kereis is one of the few companies globally to have established a comprehensive product portfolio in the field of transarterial chemoembolization (TACE). As a young company, why did Kereis choose to focus on the TACE sector?

Keruichi was founded by a seasoned team in the medical device industry; its founder, Che Haibo, was formerly a clinician at Anzhen Hospital.

At its inception, Corazon focused on the vascular intervention sector, which is divided into cardiovascular intervention, neurointervention, peripheral intervention, and oncology intervention. Among these four major sectors, Che Haibo, leveraging his extensive clinical experience, identified through an evidence-based “therapy reading” approach that oncology intervention in China was still in its introduction phase. There was a significant unmet need among both physicians and patients, and the technology was undergoing rapid development.

The field of interventional oncology encompasses both device-based and embolic products, with Keruichi simultaneously initiating the industrialization of both categories. Currently, Keruichi boasts a comprehensive and robust product portfolio in the TACE domain. It not only provides physicians with integrated solutions but also strategically positions itself for the future by developing broad-spectrum drug-eluting microspheres and radiopaque microspheres. Furthermore, the company has proactively proposed the concept of “Transarterial Immunoembolization (TAICE)” and has begun exploring and laying the groundwork for this approach.

In the treatment of hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) has become the primary therapeutic modality, with HCC management gradually evolving toward TACE-centered combined locoregional and systemic therapy. Looking ahead, as one of the key interventions in oncologic interventional therapy, what are the remaining growth drivers for the TACE market?

The primary growth driver is the further increase in the penetration rate of TACE for liver cancer treatment.The rising global incidence of liver cancer will drive the expansion of the TACE treatment market. A study published in JAMA Oncology in December 2017 indicated that the global incidence of liver cancer increased by 75% between 1990 and 2015. In China, the current penetration rate of TACE procedures is approximately 50%. With improved awareness and enhanced market education, the penetration rate of TACE is projected to rise to 70%-80% in the future.

The second major growth driver is market expansion fueled by the emergence of novel therapies and technologies., currently, emerging technologies including D-TACE and TARE account for only about 10% of the TACE market; as these new technologies gain broader acceptance, they will further drive growth in interventional oncology embolization therapies.

The third major growth driver stems from the trend toward comprehensive minimally invasive interventional approaches in clinical treatment, along with the expansion of TACE applications to a broader range of indications.Beyond liver cancer, the application of TACE is expected to expand across all solid organ tumors, including breast cancer, lung cancer, and uterine fibroids, as well as in non-oncological conditions such as hyperthyroidism, hypersplenism, and benign prostatic hyperplasia.

However, it is worth noting that to enable broader clinical applications of TACE technology, the development of broad-spectrum drug-eluting microspheres is still required.

Che Haibo, founder of KeraChi, stated: “Currently, microspheres are primarily combined with doxorubicin, an anthracycline chemotherapy agent that demonstrates strong efficacy in treating liver cancer but shows limited effectiveness against lung cancer. Therefore, there is a need for drugs with greater clinical utility for lung cancer treatment. The current preference for anthracyclines in microsphere formulations stems from the fact that microsphere surfaces carry a negative charge, while doxorubicin carries a positive charge, resulting in high drug-loading adsorption rates. However, to meet the needs of other cancer types requiring different chemotherapeutic agents, it is essential to develop broader-spectrum drug-loaded microspheres, thereby expanding their applicability across a wider range of clinical scenarios.”

The fourth major driver of market growth stems from the combination of TACE with immunotherapy and targeted therapy.In recent years, with continuous advances in molecular biology, novel agents in targeted therapy and immunotherapy have emerged successively, ushering hepatocellular carcinoma (HCC) treatment into the era of systemic therapy. Combination therapy involving multiple modalities has become a consensus in the field. The integration of transarterial chemoembolization (TACE) with immunotherapy and targeted drug therapy represents a major trend.

In-depth research and exploration of tumor vascular interventional embolization therapy will remain one of the key themes in medical technology for a considerable period to come. Nevertheless, this therapeutic approach continues to present both opportunities and challenges; significant efforts are still required to expand its technical applicability to a broader range of diseases and to achieve greater precision in treatment.