Frost & Sullivan releases the 'Report on the Current State and Development Trends of the Modified Novel Drug Industry' (with full text available for download)

Improved new drugs in China fall under category 2 of registration classification, requiring that they have not been marketed domestically or internationally. They refer to drugs that are optimized based on known active ingredients, with improvements in structure, dosage form, formulation process, route of administration, indications, etc., and possess significant clinical advantages. The NMPA classifies improved new drugs into four categories: 2.1 improvements in active ingredients, 2.2 new dosage forms and routes of administration, 2.3 new compound preparations, and 2.4 new indications.

Improved new drugs have unique advantages in terms of clinical demand and drug research and development. Improved new drugs are upgrades and improvements on already marketed drugs, emphasizing 'efficacy'. Compared with the original drugs, they have obvious clinical advantages such as enhanced efficacy, reduced side effects, and improved patient medication compliance.In drug research and development, improved new drugs possess significant advantages such as low cost, high returns, and a long lifespan.

According to data from the Biotechnology Innovation Organization, compared with new molecular entities, the success rate of improved research and development is 2.3 times higher. The costs and time of developing improved new drugs are significantly lower than those of new molecular entities. Compared with generic drugs, improved new drugs have higher professional barriers, a longer market exclusivity period, and a significantly extended lifespan.

The Report provides an in-depth analysis of all approved and investigational chemical-modified new drugs classified into categories 2.1, 2.2, and 2.3 (most drugs classified as category 2.4 are new indications for existing drugs of category 1; the relevant data statistics in the Report do not include those for category 2.4). This article will focus on elaborating on new dosage forms and routes of administration for category 2.2 drugs, with more detailed content available in the full report.

As of August 2022, the National Medical Products Administration (NMPA) has approved 24 new chemical improvement drugs classified as Class 2.1, 2.2, and 2.3. In 2021, the improvement drug era saw a harvest, with a total of 14 drugs receiving NMPA marketing approval. Overall, the therapeutic areas are concentrated in anti-infection, anti-tumor, and mental disorders. In terms of registration classification, Class 2.2 accounts for the largest proportion, followed by Class 2.1 and 2.3, mainly due to the difficulty in screening suitable active pharmaceutical ingredients for Class 2.1 drugs by altering their structures. It requires that there be differences in efficacy or toxic and side effects between the active pharmaceutical ingredient itself and its isomers, which need to be confirmed through clinical trials; Class 2.3 new compound preparations are not simply '1+1=2', facing challenges such as high barriers to preparation process technology and difficult impurity component analysis.

As of August 2022, the National Medical Products Administration (NMPA) has approved 18 new improved drugs of Class 2.2, mainly focusing on dosage form improvements for major varieties such as olanzapine, montelukast, entecavir, paclitaxel, and risperidone. In terms of dosage forms, oral film-coated preparations are predominant, mainly because the BE (Bioequivalence) experiment is only required for these, resulting in a shorter development cycle. In addition, there are also innovative dosage forms for injections among the approved drugs, such as microspheres and liposomes.

As of August 2022, 107 chemically modified new drugs are in clinical trial stages. In terms of registration classification, new dosage forms of Class 2.2 are the mainstream, while those that modify structure or are new compound preparations of Class 2.1 and 2.3 are relatively less common. In terms of therapeutic areas, they are mainly concentrated in neurological diseases. Among the 31 neurological drugs, 15 are pain-related products. This is mainly due to the higher compliance and safety requirements for medication among patients in the field of neurological diseases, making them more receptive to chemically modified new drugs.

As of August 2022, there are 77 ongoing Phase 2.2 improved new drug studies. In terms of dosage forms, common injections, sustained-release/controlled-release tablets, and oral liquid preparations account for a relatively large proportion.

From clinical trials, it is observed that unlike half of the approved improved new drugs which only require a bioequivalence (BE) trial, only two drugs in development are undergoing BE trials, both of which are oral film-coated formulations. Since the results of BE trials do not necessarily prove that a drug has clinical advantages, the difficulty of supporting the marketing of improved new drugs solely through BE trials in the future will increase.

In terms of therapeutic areas, nervous system drugs account for the largest proportion, mainly used for pain relief, sedation, and Parkinson's disease; followed by anti-tumor drugs. There have been many improvements in dosage forms for chemotherapy drugs such as paclitaxel, docetaxel, and irinotecan, as well as for nausea and vomiting caused by chemotherapy, such as the liposomal formulation of palonosetron hydrochloride from Lipomed Pharmaceuticals. In addition, eye medications also account for a significant portion, such as atropine.

The number of chronic disease patients in China continues to climb, leading to an increase in demand for improved new drugs. Driven by technological innovation and favorable policies, the market size of improved innovative drugs in China increased from 261.39 billion yuan to 323.99 billion yuan from 2016 to 2020, with a compound annual growth rate of 5.5%. It is estimated that by 2025, the market size of improved innovative drugs in China will reach 561.29 billion yuan, with a compound annual growth rate of 11.6%. By 2030, it will reach 795.17 billion yuan, with a compound annual growth rate of 7.2%.

The market for improved innovative drugs consists of innovative formulation drugs and other improved innovative drugs. From 2016 to 2020, the scale of China's innovative formulation market increased from 98.37 billion yuan to 132.67 billion yuan, with a compound annual growth rate of 7.8%. It is expected that the growth rate of the innovative formulation market will exceed that of the overall improved innovative drug market, reaching 245.88 billion yuan by 2025, with a compound annual growth rate of 13.1%. By 2030, the market scale will reach 373.33 billion yuan, with an annual compound growth rate of 8.7%.

With the continuous updating and improvement of pharmaceutical formulation technology and processes, many traditional drug dosage forms can no longer fully meet the requirements of patients with special diseases. For example, in common conditions such as diabetes and schizophrenia, patients need to take medication regularly for a long time. Traditional pharmaceutical formulations require patients to take the medication multiple times a day or weekly, which can lead to risks such as missed doses and refusal to take the medication.

Innovative formulations disperse drugs in a specially structured system, thereby changing the pharmacokinetic characteristics and tissue distribution of the drug within the body. This improves drug safety and stability, achieving reductions in toxic and side effects, frequency of dosing, and utilization efficiency. Compared to traditional dosage forms, they have more clinical advantages. Based on the difference in administration routes, innovative formulations can be divided into major categories such as oral administration, oral mucosal administration, injection administration, inhalation administration, local administration, etc.

The Report analyzes the advantages and research and development challenges of sustained-release dosage forms, oral film coatings, microspheres, microcrystals, liposomes, nanoparticles, implants, and inhalation preparations. It also provides examples of corresponding blockbuster products. For more detailed content, please refer to the complete report.

In addition, the Report lists some global listed innovative drug companies, aiming to clarify the investment value of the innovative drug space and provide an overview of financing for Chinese companies focusing on this sector.

Lipint PharmaceuticalAn innovative new drug R&D enterprise centered on innovative formulation technology, it possesses four core technical platforms with independent patented technologies: an innovative oral mucosal delivery system technology platform, a gas microsphere technology platform, a sustained and controlled release formulation technology platform, and a solubility-enhancing technology platform for poorly soluble drugs. The company focuses on unmet clinical patient needs in the fields of neurological diseases and cardiovascular and cerebrovascular diseases, and has developed 9 new drug products based on these technical platforms.

Zhengzheng Medicine:The enterprise focuses on pharmaceutical R&D, concentrating on high-end improved formulations based on DDS starting from clinical value. Currently headquartered in Shanghai Jiading, with wholly-owned subsidiaries in Zibo and Jinan, Shandong Province. Among them, Zibo and Shanghai Jiading have built laboratories of 1,800 square meters and 8,200 square meters respectively (including pilot workshops, high-end formulation laboratories, and high-activity drug laboratories). They also have clinical operation, registration, and marketing teams deployed globally, dedicated to providing compliant and efficient R&D and application services for improved new drugs for domestic and overseas enterprises.

Overseas Medicine: Established in December 2011, with its headquarters located in Guangzhou, Overseas Medicine has wholly-owned subsidiaries in Taizhou and San Diego, USA. Overseas Medicine is an international innovative new drug research and development company centered on proprietary platform technology, driven by the need to meet unmet clinical needs. Its main business is to develop new drugs suitable for the US NDA/505(b)(2), Chinese Class II chemical drugs, and global markets using independent innovation and general-purpose sustained and controlled-release platform technologies.