Insights Into the Oncology Landscape in China

Significant increases in incidence rates have made cancer a high priority in China. Despite major government reforms to reduce cancer burdens, problems remain. To fulfill its agenda in cancer innovation, China is embracing new frontiers and opportunities.

Assessing the Oncology burden in China

China has the largest number of cancer patients globally - Around 4.3 million new cancer cases were reported in 2018; the numbers are expected to grow to 6.7 million by 2040. There is an urgent and continued demand for better cancer treatment strategies in China.

China has approximately 50% of the global gastric cancer, hepatocellular carcinoma, and esophageal cancer cases. Lung cancer is the major cause of cancer mortality in China, with an overall five-year survival rate of 36%. Late diagnosis is a key factor responsible for exacerbating the disease; approximately 55 % of patients in China are diagnosed with hepatocellular carcinoma in the later stage of the disease. China also exhibits a unique epidemiological and patient profile. For instance, the EGFR mutation frequencies in Chinese patients with lung adenocarcinoma are higher than those reported in USA/European patients.

China’s oncology market represents 37% of all lung cancer, 44% of stomach cancer, and 52% of liver cancer patients globally. Though significant advances have been made in basic research and improved access to care, there are many challenges. Much more needs to be done to accelerate the growth of innovation in cancer therapy. Late diagnosis, low biomarker testing rates, and varying treatment quality are some of the hurdles which China faces. Most patients in China are diagnosed at a later stage of the disease and have limited access to an early screening. Local governments and pharma companies are working on early-screening programs for some cancers. The adoption rate of cancer-biomarker testing varies across different hospital tiers in China. In the top 500 hospitals, the testing rate for mutations such as EGFR and HER2 can reach up to 80 to 95 %; however, due to high costs and constrained availability, the next-generation sequencing testing rate is only 15 %. Treatment capacities, capabilities, and standards also vary across different classes of hospitals.

The hurdles in the road to innovation

1. The lack of new molecular entities

As high expenses and risk are involved in discovering new molecular entities, most Chinese biopharma companies avoid the gamble and focus on follow-on drugs with best-in-class potential. These strategies, although practical, might not promote innovative drug development in the long-term.

There is a severe lack of new molecular entities in phase 1 studies. The majority of the investigational new drugs or type 1 innovative drugs by the National Center for Drug Evaluation are drugs modified from existing molecular entities.

2. Lack of well-equipped study sites and severe inequality in the geographical distribution of studies

Despite the increase in phase 1 studies, there has been a scarcity of fully equipped study sites in China. There is also an imbalance in the geographical distribution of studies done across the country - 73% of the phase I studies were done in Beijing, Shanghai, or Guangzhou, the largest cities in China. Inequality in the distribution of phase 1 study sites also indicates the disparities in medical resources among different regions in China.

3. Repetitive study designs in phase 1 trials

The utilization of repetitive study designs in phase 1 trials is another loophole. The majority of the phase 1 trials in China replicate the studies done abroad and fail to include characteristics of the Chinese population. Also, most of the studies sponsored by multinational companies are pharmacokinetics or pharmacodynamic studies that assess the pharmacokinetics and pharmacodynamics profile of the Chinese population.

The role of China’s drug regulatory reform in reshaping the biopharmaceutical industry

“Drug lag” is recognized as a major issue responsible for the scarcity of innovative drugs in China. A lengthy drug review process, lack of locally developed innovative drugs, strict regulations in the clinical trial application, and import drug registration - all have hampered drug innovation. To tackle this issue, the Chinese Government issued major regulatory reforms since 2017. The reform includes fast-track clinical paths and priority review for accelerated approval, the National Reimbursement Drug List (NRDL) inclusion for reimbursement, and China’s Healthy China 2030 reform. In 2018, just a year after the regulatory reform, China witnessed a 102% increase in the number of phase 1 trials and an 85% increase in the number of phase 1 agents. The number of first-in-human studies also increased from 9% to 15% in the same year. Apart from the growth in phase 1 trials, phase 1 study sites also increased significantly and showed a more balanced geographic distribution.

With respect to treatment approaches, Immuno-Oncology (IO) therapy outstripped targeted therapy as the most popular strategy in anticancer drug R&D. The volume of immuno-oncology trials in China has increased rapidly in recent years. Immuno-oncology accounted for one-quarter of the oncology trials initiated in China during 2018-2019. Cancer cell therapy and bispecific antibody are the fastest-growing sectors. 

Reforms taken by CFDA to spur innovations

1. From strict entry, tolerant exit, to tolerant entry, strict exit

To foster a more innovation-friendly ecosystem, the China Food and Drug Administration (CFDA) modified their clinical trial regulatory policy from a strict entry, tolerant exit, to tolerant entry, strict exit. Instead of overemphasizing the approval of clinical trial applications, the current policies pay more attention to the quality control of trials and post-marketing pharmacovigilance.

2. A stricter definition of innovative drugs and a four-color light strategy

Another approach taken by the CFDA to deal with the drug lag was readjusting the regulations on drug registration of imported drugs. As per the new regulations, which came into force on Oct 10, 2017, synchronized phase 1 studies of import drugs and data from clinical trials conducted abroad can now be utilized to support local registration. Furthermore, a stricter definition of innovative drugs and a four-color light strategy have been introduced to prioritize drug reviews based on how innovative they are.

In the four-color light strategy,

· No-light drugs (highest priority) are innovative drugs that are not listed in any other country in the world;

· Green-light drugs are urgently needed drugs that are listed in other countries, but not in China;

· Yellow-light drugs are generic drugs with alternatives in China;

· Red-light drugs (unlikely to be approved) are drugs for indications that are in the restricted catalogs

Chinese Phase 1 Oncology Trial consortium 

The Chinese Phase 1 Oncology Trial consortium was founded in June 2017. The consortium focuses on facilitating cooperation between study sites, sponsors, and contract research organizations and provides a platform for sharing experience and expertise. For studies targeting less rare cancer mutations, the consortium assists in patient recruitment by referring patients with specific mutations to corresponding clinical sites.

The consortium has enabled Chinese biopharmaceutical companies to shift their focus from generic drugs to innovative drug R&D, almost tripling the number of investigational new drug filings at the center. It has also promoted novel study designs. 

Staying at the forefront

The oncology market in China is large - New frontiers and opportunities exist. Opportunities exist for pharmaceutical companies to deepen partnerships with AI and digital companies and healthcare data integrators. Many pharmaceutical companies and API manufacturing companies have started to work with local data companies on tasks from market-insight generation and patient recruitment to prospective-study development.

The high incidence of cancer in China, coupled with reforms supported by the National Medical Products Administration (NMPA), has paved the way to create a favorable environment for new biotechs focused on oncology and improved quality in oncology research.

References

· China - Global Cancer Observatory. 2018. Available at: https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf. Accessed on: 23 September 2020.

· Zhao S, Zhao H, Lv C, et al. Anticancer drug R&D landscape in China. J Hematol Oncol. 2020;13(1):51.

· Zhao S, Lv C, Gong J, et al. Challenges in anticancer drug R&D in China. Lancet Oncol. 2019;20(2):183-186.

· Wu DW, Huang HY, Tang Y, et al. Clinical development of immuno-oncology in China. Lancet Oncol. 2020;21(8):1013-1016.

· Li N, Huang HY, Wu DW, et al. Changes in clinical trials of cancer drugs in mainland China over the decade 2009-18: a systematic review. Lancet Oncol. 2019;20(11):e619-e626.

· https://www.lek.com/insights/ei/opportunities-and-patient-insights-china-oncology-market

· Managing China’s growing oncology burden.2020. McKinsey and company. Available at: https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/managing-chinas-growing-oncology-burden. Accessed on: 23 September 2020. 

About the Author:

Neeta Ratanghayra is a freelance medical writer, who creates quality medical content for Pharma and healthcare industries. A Master’s degree in Pharmacy and a strong passion for writing made her venture into the world of medical writing. She believes that effective content forms the media through which innovations and developments in pharma/healthcare can be communicated to the world."