China's First BNCT Boron Drug Granted IND Approval with Treatment Cost as Low as RMB 100,000

Recently, the official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration announced thatNeuboron (Xiamen) Biopharmaceutical Co., Ltd., a subsidiary of Neuboron Medical, has independently developed the Class 2 new drug “Boron [for Injection]”¹⁰B]falun” (abbreviated as “BPA”) has received approval for its clinical trial application (Acceptance No.: CXHL2301125), becoming the first BNCT boron drug in China and the second globally to enter registration-based clinical trials (Boron Neutron Capture Therapy, BNCT).

In March 2020, the world’s first BNCT device and the first boron drug, Steboronine, were approved for marketing in Japan for the treatment of unresectable locally advanced or locally recurrent head and neck cancer.In addition, hundreds of clinical trials have been conducted for brain tumors, malignant melanoma, lung cancer, pleural mesothelioma, liver cancer, and breast cancer, yielding favorable cure rates.

Neuboron’s self-developed domestic BPA is a broad-spectrum boron-containing drug transported via the L-amino acid transporter system (LAT-1), intended for the treatment of recurrent malignant head and neck tumors. Compared with similar products already marketed in Japan, its formulation and manufacturing process have been optimized, and the adoption of a lyophilized dosage form facilitates personalized clinical use, thereby improving compliance and accessibility in clinical practice.

BNCT utilizes thermal/epithermal neutrons with boron-containing drugs enriched in the tumor site¹⁰Boron undergoes a neutron capture reaction, producing alpha particles and 7Li nuclei, thereby precisely killing tumor cells.

Compared with conventional radiotherapy and other advanced techniques such as proton and heavy-ion therapy, Boron Neutron Capture Therapy (BNCT) offers several advantages, including short treatment duration (30–60 minutes per session, with cure achievable in as few as 1–2 sessions), precise targeting, minimal side effects, favorable clinical efficacy, and controllable costs (domestic manufacturers can effectively keep the treatment cost at approximately RMB 100,000). It is hailed as the “fifth modality” of cancer treatment, following surgery, conventional radiotherapy, anticancer drugs, and immunotherapy.

However, from a clinical perspective, BNCT has not yet been widely adopted in clinical practice. Some small-sample clinical studies suggest that BNCT can achieve superior efficacy compared to conventional radiotherapy for certain specific patient populations. Mechanistically, the indications for BNCT primarily depend on the characteristics of the neutron beam irradiation system used (flux and range) and the degree of boron drug accumulation within the tumor. Drugs used for BNCT must exhibit good targeting capability, meaning they should accumulate in tumor tissue while showing minimal distribution in normal tissues and rapid clearance.

Currently, clinical research on BNCT is primarily focused on the treatment of locally recurrent tumors. Clinical study results using boron-containing drugs (BPA and BSH) and irradiation systems (reactors and AB-BNCT) indicate thatBNCT demonstrates prominent advantages in the treatment of central nervous system tumors, head and neck tumors, and malignant melanoma of the skin and mucosa.

Over the past few decades, the development of BNCT has been constrained by the difficulty in obtaining neutron beams from nuclear reactors. With the emergence and maturation of accelerator-based neutron source technologies over the last decade, the potential of BNCT is gradually being realized.

In March 2020, the accelerator-based BNCT system at Minami Tohoku Hospital in Japan was approved for market launch due to its outstanding clinical performance in the indication of head and neck cancer, and it was included in Japan’s national health insurance reimbursement scheme in June of the same year.

China also started early and developed rapidly in the field of BNCT radiotherapy. In the 1990s, China began technical research on BNCT.

In 2009, Zhou Yongmao, an academician of the Chinese Academy of Engineering and an expert in nuclear reactor engineering, led the construction of a neutron irradiator based on a micro nuclear reactor and successfully treated multiple patients with melanoma. In 2014, the world’s first dedicated BNCT nuclear reactor neutron source facility (IHNI-1), designed and built under the leadership of Academicians Zhou Yongmao and Wang Zhongcheng, successfully conducted clinical trials of reactor-based BNCT for cutaneous melanoma.

On the industrial front, domestic anti-cancer boron drugs have also seen a string of good news in recent years.

In 2019, Neuboron Therapy System Ltd. completed the production of multiple batches of high-boron-enriched active pharmaceutical ingredients (APIs) and multiple batches of pilot-scale formulations. Relevant non-clinical studies further demonstrated that domestically produced BPA combined with neutron irradiation achieved a tumor inhibition rate of over 85%, suggesting that BNCT exhibits favorable efficacy in both head and neck cancer and glioma models.

In 2021, Chongqing Gaojin Biotechnology Co., Ltd. announced that it had successfully developed the first boronophenylalanine (BPA) boron drug targeting malignant tumors such as melanoma, brain cancer, and glioma, based on the non-radioactive isotope boron-10. Through Boron Neutron Capture Therapy (BNCT), a variety of specific cancers can be cured in as little as 30 minutes. Public information indicates that Gaojin Biotechnology’s product is the first anti-cancer boron drug in China to complete pilot-scale testing.

Currently, Argentina, Belgium, China, Finland, Israel, Italy, Japan, South Korea, Russia, Spain, and the United Kingdom are all actively developing AB-BNCT projects., research teams in several countries have conducted multiple clinical studies on BNCT for solid tumors using reactor neutron sources, demonstrating its significant therapeutic advantages in treating intracranial malignant tumors, head and neck cancers, and cutaneous and mucosal malignant melanomas.

Among them, Japan currently has the largest number of AB-BNCT projects, with a total of 10 BNCT centers in the planning and operational stages.In fact, due to factors such as high R&D costs and intellectual property fees, the prices of original foreign boron drugs are exorbitant. In Japan, even after being included in national health insurance, the cost of BNCT treatment remains as high as 300,000 RMB.

If China’s BNCT clinical equipment rapidly enters the market, the treatment cost for cancer patients is expected to drop to RMB 100,000–150,000, representing a reduction of more than half compared with the cost in Japan. In fact, the development of BNCT in China has reached a stage where clinical research and industrialization are proceeding in parallel, with an increasing number of enterprises and medical institutions beginning to focus on and engage in BNCT-related projects.

According to publicly available data,Currently, there are more than 10 BNCT projects in China that are either operational, under construction, or planned.Including: IHNI (Kaibaite), Xiamen Hongai Hospital, Qilu Hospital of Shandong University, Gaoxin Campus of Taian Central Hospital in Shandong Province, Borong BNCT Project, CNNC Changsha Cancer Hospital, Union Hospital Affiliated to Fujian Medical University (Mazu Health City), Dongguan Hospital Affiliated to Southern Medical University, Pengbo Boao Boron Neutron Hospital, BNCT Nuclear Medicine and Health Industry Demonstration Project, and Guangdong Medical University Songshan Lake Science City.

Notably, in the Xiamen region, Neuboron Therapy System Ltd. collaborated with Xiamen Hongai Hospital to commence construction of China’s first accelerator-based BNCT tumor treatment center—the largest single facility of its kind globally and the most comprehensively equipped—in 2019. The project was successfully completed in February 2021. On October 9, 2022, the center initiated safety studies on the first cohort of clinical oncology patients, marking the first use of accelerator-based BNCT technology within a hospital setting in China.China has also become the second country in the world, after Japan, to possess accelerator-based BNCT technology and operational capabilities.

In addition to Neuboron, other key players in the research, development, and industrialization of boron-based drugs in China include HEC Research Institute, Gaojin Biopharma, Dongcheng Pharmaceutical, Gaobo Biotech, and Poly Pharm.

Not only is the boron-based drug industry experiencing robust growth, but overall, the radiopharmaceutical sector appears to have remained resilient against the recent capital winter. Instead, the entire industry has been revitalized by the approvals of Lutathera and Pluvicto. Companies such as Grand Pharma, Hengrui Medicine, Sinotau Pharmaceuticals, and Hexin Pharmaceuticals are demonstrating strong momentum, further accelerating the pace of radiopharmaceutical R&D and financing. The introduction of landmark policies, including the Medium- and Long-Term Development Plan for Medical Isotopes (2021–2035) and the Technical Guidelines for Clinical Evaluation of Radiopharmaceuticals for Internal Therapy, has also sent highly positive signals to the market.

Radiopharmaceuticals have demonstrated their advantages to the market, including precise targeting, potent cytotoxicity, limited off-target damage, and integrated theranostic capabilities, gradually emerging as the next major wave of innovation in oncology treatment. According to statistics from VCBeat Research Institute, there are 75 radiopharmaceutical pipelines under development in China, while nearly 7,000 pipelines abroad have entered clinical trials, indicating that innovative radiopharmaceutical R&D is entering a period of high productivity. Let us look forward to the rapid fruition of advancements in the radiopharmaceutical field to meet the substantial unmet clinical needs.

References:

1. Boron Neutron Capture Therapy (BNCT) 《China’s First! Neuboron’s Domestically Produced Boron Drug Approved for IND Clinical Trials》

2. Dongguan Releases “Latest News! Cancer’s ‘Fifth Therapy’ Set to Enter Clinical Trials in Dongguan Next Year!”

3. YAOZHI: “Nuclear Explosion” Within Tumor Cells: Global Analysis of Boron Neutron Capture Therapy in Development