Pamedic Spotlight｜Nuclear Drugs, China Poised for Take-off

Nuclear drugs, also called radiopharmaceuticals and nuclide drugs, are pharmaceutical preparations consisting of radioisotopes paired with molecular reagents specialized in locating specific organs and tissues, used for imaging diagnosis and clinical treatment.

1.Classification of Nuclear Drugs

Nuclear drugs can be categorized into diagnostic and therapeutic nuclide drugs according to their use.

Diagnostic nuclear drugs include drugs for organ imaging and drugs for function determination. Combined with SPECT or PET, they can study the function and metabolic process of drugs in the living body at the molecular level, realizing rapid, non-destructive and real-time imaging of physiological and pathological processes, and providing a means of early diagnosis and timely treatment in the real sense.

Therapeutic nuclear drugs are radioactive drugs that patients take orally or by injection to make them highly concentrated on diseased tissues, using the rays emitted by the nuclides to produce a localized biological effect of ionizing radiation to inhibit or destroy the diseased tissues. Currently, the drugs are used in the treatment of thyroid diseases, tumor treatment and so on.

2.Market Size for Nuclear Drugs

The global nuclear drugs market size shows a booming development trend. According to Medraysintell, the global nuclear drug market size was approximately USD 6 billion in 2019, with diagnostic drugs dominating the market. With more and more therapeutic drugs coming to the market, the global nuclear drug market size is expected to reach about $30 billion by 2030.

Against this global backdrop, China's nuclear drug market is rapidly emerging. According to Frost & Sullivan, the compound annual growth rate of nuclear drugs is second only to that of biologics, and its growth trend is ahead of other drug types.

Despite the rapid growth of China's nuclear drug market, its share in the global market is only 6%. Based on the data that China had about 4.5 million new cancer patients in 2020 and 18F-FDG PET/CT used for cancer diagnosis are less than 1 million times in 2020, China's nuclear drug market has huge demand space. Meanwhile, the scale of the nuclear drug industry will continue to expand under policy support. The nuclear drug industry is expected to reach a market size of 16.2 billion yuan in 2025. It is expected that the installed capacity of PET/CT and SPECT/CT will continue to grow at an annual rate of 12% in the next 10 years.

3.Barriers to the Nuclear Drug Industry

At present, China's nuclear drug industry faces multiple barriers, which is manifested in the following aspects:

Raw Material "Strangling"

Medical isotopes are the main raw material for nuclear drugs, but most medical isotopes rely on imports. While some isotopes such as 131I and 177Lu are able to be produced domestically, other isotopes are mostly still dependent on imports from overseas suppliers. And overseas suppliers often prefer to work with existing customers rather than establish new business relationships, which increases the instability of the supply chain. Stable supply of medical isotope raw materials has therefore become a major challenge for new entrants to the nuclear medicine industry.

High Technical Barriers

The production of radioisotopes requires large nuclear reactors or cyclotrons, the construction and operation of which require complex technologies and strict regulations. The manufacture of radiopharmaceuticals involves complex nuclear technology, including radiotracer and radiation detection techniques. In addition, manufacturers need to have qualified radiation protection equipment and technicians. All of the above limitations constitute extremely high technical barriers.

Tight Regulation

The specificity and strictness of the regulatory system are also one of the challenges facing the nuclear medicine industry. The nuclear drug industry is highly regulated in China and involves very complex and strict laws and regulations. In addition to conventional pharmaceutical regulations, the nuclear drug industry needs to comply with numerous special requirements, such as the Measures for the Administration of Radioactive Pharmaceuticals.

Short Half-life Time——Restrictive Time Limit of the Delivery

Isotopes commonly used in nuclear medicine diagnosis, such as 99mTc (half-life of 6 hours) and 18F (half-life of less than 2 hours), have a short half-life, which puts forward extremely high requirements for logistics and distribution.

4.Development Trend of Nuclear Medicine in China

Policy is one of the most important driving forces for the development of the nuclear medicine industry. The Chinese government has issued a number of policies related to nuclear drugs, aiming at solving the problem of raw material supply, promoting the industry's innovation and development, and thus improving the independent production capacity of nuclear drugs. Meanwhile, technological innovation is also an important engine for the development of the industry, and the popularization of new targeted radioligand therapies and PET-CT technology will further promote the development of the nuclear drug industry as well.

Policy-driven: The government has circulated a series of policies to support the development of the nuclear medicine industry, such as the Medium- and Long-Term Development Plan for Medical Isotopes (2021-2035), which aims at reducing dependence on imported radioisotopes and accelerating the independent production capacity of domestic medical isotopes.

Technology-driven:As targeted radioligand therapy and diagnostic integration develops, the efficacy of innovative nuclear drugs for the treatment of tumors has been gradually remarkable. Novel nuclear drugs such as 177Lu-Dotatate have been approved by the FDA for the treatment of gastroenteropancreatic neuroendocrine tumors. The PRRT group showed a 79% reduction in the risk of tumor progression or death compared to long-acting octreotide and the European Society of Neuroendocrinology has raised it to a first-line treatment option in its guidelines.

Popularization of PET-CT Technology: The popularization of PET-CT technology has also promoted the development of the nuclear medicine industry. PET-CT, as an advanced imaging technology, has been widely used in clinical medicine, especially in cancer diagnosis. The National Comprehensive Cancer Network (NCCN) has applied PET-CT in the diagnosis of a wide range of cancers, including 36 types of cancers, such as breast cancer, non-small cell lung cancer, colon cancer, rectal cancer, esophageal cancer and gastric cancer, etc. In October 2018, the National Healthcare Commission issued the Circular on the Release of the Large-scale Medical Equipment Configuration Planning for the Years 2018-2020, which requires that by the the end of 2020, PET-CT national planning configuration 710 units, a total of 377 new units. Under the policy, PET-CT equipment volume will imcrease year by year, pulling nuclear medicine diagnosis of the number of cases increased significantly, and thus promoting the application of diagnostic and therapeutic nuclear medicine.

5. About Future

In the future, the nuclear drug industry is expected to make new progress in several directions, including new targets, new ligands, new radioisotopes and combination therapies.

New Targets: Researchers are developing radiopharmaceuticals against a variety of new biological targets, such as CXCR4, FAP3, and NTR1, as well as CCK2-R, GRP-R, and integron receptors.

New Ligands: In addition to traditional peptides and small molecules, monoclonal antibodies and nanoantibodies are expected to fulfill their advantages as targeting ligands. For example, nano-antibodies are characterized by small size, high solubility and good tissue penetration, etc. Bicycle Therapeutics' bicyclic peptide technology introduces chemical modifications into peptides, thus making bicyclic peptide molecules combine the characteristics of antibodies, small molecules and peptides, providing a ligand with high affinity, selectivity and permeability for the development of radiopharmaceuticals with precise targeting of tumor antigens.

New Radioisotopes: Expand the range of therapeutic radioisotopes by making greater use of alpha-particle therapy, which takes effect in tissues over a shorter distance than beta rays, precisely killing the targeted cancer cells without harming surrounding healthy tissues.

Combination Therapy:Utilizing synergistic combination therapeutic pathways, such as combining radiopharmaceuticals with immune checkpoint inhibitors, "synthetic lethal" drugs that inhibit DNA repair, etc., to enhance the clinical effects of radiopharmaceuticals.

Restricted by the high requirements of diagnostic equipment, nuclide raw materials supply, technical level, China's nuclear drug innovation is still in the primary stage, with fewer companies devoted to the development of innovative nuclear drugs. However, with the advancement of science and technology, the support of policies, and the concerted efforts of the industry, China's nuclear drug innovation will usher in an accelerated development of the time, and the market will also continue to expand. As an emerging high-tech enterprise in isotope research, production and supply, Pamedic Holdings will continue to plough deep into the field of radiotherapy and promote the rapid development of the industry ecology.