ll

Leading Edge

Commentary
Challenges and opportunities in oncology
drug development and clinical research in China
Feng Wang,1,2,4 Dan-Yun Ruan,2,3,4 and Rui-Hua Xu1,2,*
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong

Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou 510060, P.R. China
2Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou

510060, P.R. China

3Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong

Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou 510060, P.R. China
4These authors contributed equally

*Correspondence: [email protected]
https://doi.org/10.1016/j.cell.2024.02.040

As one of the world’s most populous countries, China bears a heavy burden and a broad spectrum of can-
cers, including unique types, providing a unique environment for drug research and development. In recent
years, China has leapt forward in oncology drug development and clinical trials, presenting new opportunities
and challenges.

Introduction Comparing the number of pivotal clin- 10 new anti-cancer drugs from 10 phar-
Cancer is a major threat to human health. ical trials for innovative drugs in China, maceutical companies showed that the
In particular, China faces a substantial the United States (US), Europe, and median time to develop a new product
burden, with the highest numbers of new Japan from 2016 to 2023 reveals that was 7.3 years (range: 5.8–15.2 years),
cases (4.57 million) and deaths (3 million) China has surpassed Europe since 2020 with a median cost of $648.0 million
accounting for 23.7% and 30%, respec- and has exceeded the US in 2023 (range: $157.3 million–$1.95 billion).5
tively, of the world’s total population.1 (Figure 1B). From 2011 to 2020, the num- Based on commercial considerations,
Hence, the increasing prevalence of can- ber of phase I clinical trials in mainland many biopharmaceutical companies in
cer in China has created a pressing de- China slightly increased, with the number China have opted for ‘‘me-too’’ or ‘‘fast-
mand for effective therapeutic solutions. of trials increasing rapidly beginning in follow’’ drugs that are less risky and faster
China’s pharmaceutical industry is 2018.4 China has accounted for nearly to develop. This strategy, to some extent,
now entering a new phase of drug inno- one-third of global clinical trial activities, directly contributes to the target duplica-
vation and has become the world’s sec- with the proportion showing a rising trend tion and overlap of indications. Figures
ond-largest pharmaceutical market in in recent years (Figure 1C). Specifically, 2A and 2B show the distributions of the
terms of drug research and development China’s share of oncology trials has risen top 10 targets and oncology targets under
(R&D) pipelines and the number of new significantly (Figure 1D). development by pharmaceutical enter-
products.2 Over the past decade, clinical China is rapidly ascending to a leading prises in China and the US. In oncology
development and regulatory reviews in position in R&D investment and clinical pipelines, the most numerous drug types
China have changed significantly, with research worldwide, but there is still a include CD19 and PD-1/PD-L1 mono-
reforms aimed at encouraging the devel- gap in the innovation capacity of the phar- clonal antibodies and targeted therapies
opment of innovative drugs, especially maceutical sector compared with that of for EGFR or HER2. According to the top
for rare, serious, or life-threatening dis- developed countries in Europe and the 10 target concentration rate, China’s
eases, to ensure that patients have ac- US. In the following sections, we discuss drug targets are more likely to focus on
cess to timely treatment.3 Figure 1A the current challenges and existing prob- popular targets. Among all therapeutic
shows the number of investigational lems of oncology drug research and targets, China’s approved targets ac-
new drug (IND) applications and new development in China, as well as im- counted for the highest proportion
drug applications (NDAs) for innovative provements and opportunities, the under- compared to the US and the rest of the
drugs in China from 2018 to 2022. The standing of which will help accelerate the world. Notably, 70% of the world’s new
first submission of IND applications has development of anti-cancer therapeutics targets in drug development have no
shown a year-over-year increasing trend; and benefit cancer patients worldwide. products entering the clinical stage in
among them, approximately 80% are China (Figure 2C). These findings indicate
domestically produced. Notably, the Challenges that drug development in China still fo-
number of NDA approvals remains rela- Homogeneity of new targets cuses on fully validated targets and that
tively small, and the main therapeutic The challenges of new drug R&D include the exploration of new targets needs to
category approved for the first IND appli- high costs, long development cycles, be improved. One main reason is related
cation is oncology. and low success rates. An evaluation of to economic factors: developing products

1578 Cell 187, March 28, 2024 ª 2024 Elsevier Inc.

 ll
Commentary

with mature targets may involve less risk,

and the technical requirements may be
relatively low. Race, epidemiology, and
indications also affect the target distribu-
tion. For example, among the top 10 can-
cers in China, the domestic incidences of
gastric cancer, liver cancer, esophageal
cancer, and cervical cancer are signifi-
cantly greater than those in the US, which
means that drugs for the treatment of
these cancer types may have very
different market prospects. Additionally,
their indications may be prioritized when
companies are conducting clinical stu-
dies. The purpose of drug R&D is to
meet the medical needs of patients, and
the homogeneity of targets may, to a
certain extent, reduce the cost of treat-
ment. However, due to the heterogeneity
of tumors, more innovative and differenti-
ated therapies are needed to benefit more
patients.
Insufficient collaboration between
the bedside, science, and
pharmaceutical industries
As of 1 July 2021, among 2,251 domestic
investigational agents across all therapeu-
tic areas in China, only 418 (18.6%) were
first-in-class (FIC) agents, of which
oncology accounted for more than half
(55%) of the agents.6 This reflects a lack
of FIC anti-cancer drugs in China. The
term ‘‘first-in-class’’ refers to original inno-
vation through the use of new and unique
mechanisms of action. The development
of FIC drugs relies on innovative molecular
target discovery and novel agent design.
Bedside-to-bench translational studies,
which focus on translating findings from
clinical observations back to basic sci-
ence, play a crucial role in bridging the
gap between clinical practice and labora-
tory research. However, some challenges
hinder the progress of bedside-to-bench
translational studies in China. These limi-
tations include the lack of communication
and collaboration between clinicians and
basic scientists as well as limited bioma-
rker exploration by pharmaceutical com-
panies. Clinicians usually have a heavy
workload and time constraints and may
Figure 1. Current status of innovative drug applications and clinical trials in China not have the expertise to communicate
(A) The number of innovative new drug IND and NDA applications from 2018 to 2022 according to the
CDE’s 2022 Annual Drug Evaluation Report.
(B) Comparison of the number of pivotal trials conducted for innovative drugs in China, the United States,
Europe, and Japan from 2016 to 2023, according to the region in which trials were carried out (chemical (D) The number and China’s share of global
drugs and biological drugs only). Pivotal trials refer to the key trials conducted for drug registration. Data oncology trials from 2016 to 2023. Data from
from TrialCube database on Pharmcube. PharmaGo database on Pharmcube.
(C) The number and China’s share of global clinical trials from 2016 to 2023. Data from PharmaGo IND, Investigational New Drug; NDA, New Drug
database on Pharmcube. Application; CDE, Center for Drug Evaluation.

Cell 187, March 28, 2024 1579

 ll
Commentary

effectively with scientists. Similarly, scien- Drug R&D Power Ranking, the total R&D China to identify and develop new FIC
tists are experiencing publication pressure investment of the top 10 local companies drugs for cancer treatment and improve
and limited access to clinical data or pa- is as high as 45.378 billion yuan ($6.394 the market environment.
tient samples to validate their findings. In billion), a 16-fold difference. One crucial Improvement of the regulatory
addition, ethical considerations and regu- factor is that companies have not environment
latory policies may also impose limitations achieved good business returns. Globally, The Chinese government has imple-
on accessing patient data. Most anti-can- the top 10 pharmaceutical companies mented policies and initiatives to support
cer drugs developed in China are derived have more than half of the products listed the growth of the pharmaceutical industry
from industry, and the contributions from on the market, and the cash flow gener- and promote innovative clinical research.
academia are relatively small.7 At present, ated by these products will further The ‘‘Three-year Action Plan for Cancer
assessments of Chinese universities and strengthen the competitive advantage of Prevention and Treatment in China
institutes have focused mainly on papers, enterprises, where there is still a yawning (2015–2017)’’ issued in September 2015
patents, and research funds; thus, aca- gap between Chinese companies. More- clearly encouraged oncological clinical
demic institutions are more inclined to pro- over, many pharmaceutical manufac- research. A series of regulatory reform
duce theoretical knowledge. This is less turers in China are small-scale enter- measures for drug supervision and man-
conducive to economic and social real- prises. The homogeneity of products agement have also been introduced. In
ity-oriented innovation breakthroughs. intensifies competition between com- addition, since 2017, China has been the
Another problem is that China has plenty panies, and progress in domestic R&D eighth regulatory member of the Inter-
of doctors but still lacks systematically also proposes greater requirements for national Conference on Harmonization
trained clinician-scientists who are well- quality and efficiency. These reasons (ICH), transforming its pharmaceutical
versed in research. In recent years, some make it difficult for companies to support regulatory authorities and industry and
of China’s top colleges and universities R&D with sufficient financial resources research institutions to adhere to the inter-
have begun training programs for clini- and to pursue new drug discovery. nationally accepted ICH Guidelines. The
cian-scientists, such as the ‘‘Tsinghua Regional disparities in medical National Medical Products Administration
University Medical Experimental Class’’ resources (NMPA), formerly known as the China
and the ‘‘Zhi-Guang Program of Sun Yat- China has a large and well-compliant pa- Food and Drug Administration (CFDA),
Sen University Cancer Center.’’ tient population and a large health care has made significant improvements to
Weak international system, which could be advantageous the clinical trial agency accreditation sys-
competitiveness of domestic for conducting clinical trials; however, tem, such as eliminating some unneces-
enterprises the specialized staff and experienced sary and lengthy certification processes
Compared with US and some European and well-equipped study sites that can for new trials registered by medical facil-
companies, most Chinese pharmaceu- administer high-quality clinical trials are ities and shifting its focus toward ensuring
tical companies are still in the early stages still very limited, with serious inequalities better quality control in clinical trials and
of new drug development, and the R&D in geographical distribution. A major postmarketing pharmacovigilance. IND
capabilities of pharmaceutical enterprises reason is that medical resources are and NDA processes have been optimized.
need to be strengthened. China lacks en- mainly distributed in economically devel- A very substantial change is the approval
terprises with international influence. As oped eastern coastal cities and densely time for a clinical trial application (CTA).
the pharmaceutical invention index and populated middle regions. In 2017, China In the past, CTA approval took approxi-
pharmaceutical innovation index were re- had 180 phase I trials, which were mately 10 months to 2 years, compared
ported (from IDEA_Pharma) in 2020, completed by 18 facility sites. A total of to the US (30 days) and European Union
Jiangsu Hengrui Pharmaceuticals Co., 132 (73%) of these studies were per- (60–105 days) approval times. In 2018,
Ltd. was listed for the first time, ranking formed in Beijing, Shanghai, or Guangz- the 60 working day investigational new
13th and 15th, respectively. This was the hou, the three largest cities in China.8 drug filing system was adopted, greatly
first time that Chinese pharmaceutical This geographical difference highlights shortening the time frame.8 Since 2022,
companies had been included in the in- the regional disparity of medical re- more than 100 drug R&D guidelines and
dex. In the latest list from 2023, BeiGene sources in clinical research in China. consultation drafts have been released
Ltd. was the only Chinese company to by the NMPA that regulate clinical trials
enter the top ten, ranking seventh in the Opportunities in oncology and rare diseases, including
pharmaceutical invention index list. The Chinese pharmaceutical industry has guidance on emerging therapeutics such
Pharm Exec’s 2023 Global Biopharma- experienced significant growth and devel- as gene therapy, cell therapy, oncolytic vi-
ceutical Industry Top 50 list based on opment over the last few decades. With a rus therapy, etc. Recently, the National
sales data for prescription drugs in the large domestic market and abundant clin- Natural Science Foundation of China has
2022 fiscal year lists only four Chinese ical resources, China has become an also announced that they are going to
pharmaceutical companies, the top attractive destination for pharmaceutical fund clinical projects and investigator-
ranking being Sino-Biopharmaceutical at companies to invest in research, develop- initiated trials. These policies have accel-
rank 39. The total investment of the top ment, and manufacturing. Ongoing efforts erated the process of drug marketing
10 companies in the world is $101.676 are being made by the government, insti- and are associated with a significant in-
billion. According to the 2023 China tutions, and pharmaceutical companies in crease in anti-cancer drug trials.

1580 Cell 187, March 28, 2024

 ll
Commentary

Figure 2. Target distribution of innovative drugs

(A) Top 10 drug targets and the target concentration rate in China and the United States.
(B) Top 10 oncology drug targets and the target concentration rates in China and the United States.
(C) Proportion of approved drug targets being studied in China, the United State, and globally. Drug research and development status of global innovative drug
targets in China. Data from NextPharma database on Pharmcube.

Increasing capacity for clinical to ASCO meetings, with the keyword This illustrates how China’s growing
research ‘‘China’’ occurring 350 times in the 2022 oncology burden is both a challenge and
China has progressively aligned their clin- ASCO agenda. Concurrently, more thera- an opportunity for clinical drug research.
ical research environment with global peutic agents and regimens developed in The large number of patient resources is
benchmarks. The number of oncology ar- China have been applied worldwide in conducive to the rapid development of
ticles published by Chinese principal in- clinical practice. The US FDA approved clinical trials, especially for some unique
vestigators from hospitals or academics zanubrutinib (BRUKINSA) for the treat- types of cancers that are more prevalent
in top journals is growing. Increasing ment of mantle cell lymphoma in 2019, in China than in the rest of the world,
numbers of Chinese drug originals have the first new chemical entity discovered such as esophageal squamous cell carci-
received international recognition. In in China to receive initial international noma, liver cancer, nasopharyngeal can-
2011, China-originated innovations first approval. In 2023, four Chinese original cer, gallbladder cancer, etc. Over the
appeared in American Society of Clinical anti-tumor drugs were approved over- years, China’s healthcare system has
Oncology (ASCO) meetings. Since then, seas: tislelizumab (TEVIMBRA) approved made great achievements in improving
more Chinese studies have made exciting by the European Medicines Agency healthcare services and strengthening
clinical progress in the oncology space. In (EMA), and avapritinib (AYVAKIT), toripali- medical infrastructure, and the disparities
2022, Chinese pharma contributed 19 oral mab-tpzi (LOQTORZ) and fruquintinib in cancer diagnosis and treatment be-
presentations and more than 70 posters (FRUZAQLA) approved by the US FDA. tween China and the US have gradually

Cell 187, March 28, 2024 1581

 ll
Commentary

narrowed. An increasing number of Chi- tries, but this method requires strong ca- ising biopharmaceutical markets. Given
nese physicians have shown a highly pos- pabilities and has a greater risk. The sec- the continuously rising demand for new
itive attitude toward clinical research and ond method is cooperating with large oncology therapeutic agents, it is worth-
translational medicine.9 In addition, the international pharmaceutical companies while to think about how to further support
improved ability to evaluate biomarkers to bring local drug products to the global oncology clinical research and new drug
and its relatively low cost in China market and conducting clinical trials led R&D. For example, cooperation between
have facilitated translational biomarker by Chinese principal investigators. No basic science and clinical medicine
research accompanied by clinical trials. matter what form it takes, clinical trials should be strengthened, and a platform
This is extremely important because the play a vital role. As demonstrated, several of translational medicine should be estab-
number of targeted therapies and immu- new drugs developed in China have lished in institution-based hospitals. By
notherapies requiring biomarker assess- recently been approved by the FDA. training physician-scientists who can
ment for patient selection in clinical trials Notably, the approval of toripalimab is integrate scientific research and medical
is increasing. All these provide a big op- based on the findings of JUPITER-02, practice, in addition to becoming doctors,
portunity to lead clinical trials and develop a clinical trial conducted in a Chinese- they can also be competent in leadership
new agents in China. dominated Asian population.14 The re- roles in academic institutions, biotech-
Although the number of global FIC sults from the phase 3 FRESCO-2 and nology companies, and pharmaceutical
drugs in China is still small, the mode of FRESCO trials support the approval of companies. The collaboration between
drug development is changing from fruquintinib, and the FRESCO trial was a innovators should be promoted to form
‘‘me-too’’ to FIC, and the proportion of multicenter, placebo-controlled trial con- diversified business cooperation models
advanced technology-based innovative ducted in China.15 among academies, research institutes,
agents is also increasing. We are encour- Licensing is another crucial aspect of and enterprises; policy guidance for orig-
aged by the growing collaboration and expanding into larger markets: through inal innovation; special fund support; and
communication between clinicians and licensing agreements, companies can encouragement of research and develop-
scientists. Government funding and sup- obtain new products, technologies, and ment of FIC drugs and support for small
port for translational research initiatives intellectual property. Before 2015, obtain- innovative bio-enterprises. We believe
can help address the problems faced by ing new products in China was mainly that these collaborative endeavors will
both clinicians and scientists. A growing based on license-in because pharmaceu- enable more China-originated drugs to
number of clinicians are trained scientifi- tical companies had weak independent integrate into the global market, actively
cally and are realizing the importance of R&D capabilities and introduced new participate in cancer therapeutics, and
incorporating translational research de- foreign drugs for clinical development. keep contributing Chinese wisdom and
signs into clinical trials. In multiple cohorts However, with the improvements in strength to medical science.
of a phase 1/2 study of the domestic drug domestic R&D capabilities and the regula-
toripalimab, biomarker testing for patients tory environment, China’s license-out ACKNOWLEDGMENTS
was prospectively designed and incorpo- products have gradually increased in
rated into the protocol, which greatly recent years. Licensing new drugs over- This work was supported by the National Natural
contributed to the discovery of predic- seas to expand global markets has Science Foundation of China (82321003 to R.-
tive biomarkers and resistance mecha- become an optimal choice for domestic H.X.); CAMS Innovation Fund for Medical Sciences
(CIFMS) (2019-I2M-5-036 to R.-H.X); the Scie-
nisms.10–13 These acts have led to a pharmaceutical companies. There are
nce and Technology Program of Guangzhou
tremendous increase in the number of do- continuous breakthroughs in the number (202206080011 to F.W.); and the Fundamental
mestic pharmaceutical companies and of large deals. For instance, in 2023, Research Funds for the Central Universities, Sun
the development of new drugs. The Chi- KYM Biosciences entered into a collabo- Yat-sen University (22yklj06 to F.W.). We thank
nese pharmaceutical industry is poised ration and license agreement with Astra- Zhi-Min Yang and Yuan-Yuan Song of the Center
for continued growth and development, Zeneca for its potential FIC antibody for Drug Evaluation, China National Medical Prod-
ucts Administration, Beijing, China, who provided
with increasing investment in research drug conjugate targeting Claudin 18.2,
information and assisted in carrying out this work.
and development, expanding interna- CMG901, for an upfront payment of $63 We thank Junshi and PharmCube for their collabo-
tional collaborations, and a focus on inno- million with potential development and ration in providing us with the authority and data
vation and technological advancement. sales-related milestone payments of up support of the Pharmcube database. We thank
Pharmaceutical companies to $1.1 billion. Cases like this give local Dr. Hao-Xiang Wu for the data cleansing and
expanding into larger markets pharmaceutical companies more encour- data processing.
In the past five years, new anti-cancer agement and confidence to increase
drugs marketed in China have been up- future investment, which may further pro- DECLARATION OF INTERESTS
dated at a rapid pace; moreover, domes- mote the development of innovative anti-
tic enterprises are actively promoting new cancer drugs in China. R.-H.X. reports receiving speaker honoraria from
products in overseas markets in two main Bristol Myers Squibb, Roche, MerckSerono,
Hutchison, Hengrui, Junshi, Qilu, CPPC, and Hen-
ways. The first is to carry out international Conclusion
lius and participates on advisory boards for Astel-
multi-center clinical trials and then use Today, China is an important player in the las, MSD, AstraZeneca, Junshi, Hengrui, BeiGene,
these data to acquire NDA applications field of oncology clinical research and is Innovent, CPPC, and Keymed. All other authors
in drug administration of developed coun- considered one of the world’s most prom- declare no competing interests.

1582 Cell 187, March 28, 2024

 ll
Commentary
REFERENCES 553–554. https://doi.org/10.1038/d41573-022- geal Carcinoma: A Phase II Clinical Trial
00058-6. (POLARIS-02). J. Clin. Oncol. 39, 704–712.
1. Qi, J., Li, M., Wang, L., Hu, Y., Liu, W., Long, Z., https://doi.org/10.1200/JCO.20.02712.
7. Li, G., Qin, Y., Xie, C., Wu, Y.L., and Chen, X.
Zhou, Z., Yin, P., and Zhou, M. (2023). National
(2021). Trends in oncology drug innovation in 12. Wang, Z.X., Cui, C., Yao, J., Zhang, Y., Li, M.,
and subnational trends in cancer burden in
China. Nat. Rev. Drug Discov. 20, 15–16. Feng, J., Yang, S., Fan, Y., Shi, J., Zhang, X.,
China, 2005-20: an analysis of national mortal-
https://doi.org/10.1038/d41573-020- et al. (2022). Toripalimab plus chemotherapy
ity surveillance data. Lancet Public Health 8,
00195-w. in treatment-naı̈ve, advanced esophageal
e943–e955. https://doi.org/10.1016/S2468-
8. Zhao, S., Lv, C., Gong, J., Wenfeng, F., Hu, X., squamous cell carcinoma (JUPITER-06): A
2667(23)00211-6.
Ba, Y., Xiaoyuan, C., Zhimin, Y., Shen, L., and multi-center phase 3 trial. Cancer Cell 40,
2. Kong, L., Li, Q., Kaitin, K.I., and Shao, L. 277–288.e273. https://doi.org/10.1016/j.ccell.
Zhang, L.; Chinese Phase 1 Oncology trial
(2023). Innovation in the Chinese pharma- 2022.02.007.
Consortium (2019). Challenges in anticancer
ceutical industry. Nat. Rev. Drug Discov.
drug R&D in China. Lancet Oncol. 20, 183– 13. Chen, Y.X., Wang, Z.X., Jin, Y., Zhao, Q., Liu,
22, 12–13. https://doi.org/10.1038/d41573-
186. https://doi.org/10.1016/S1470-2045(18) Z.X., Zuo, Z.X., Ju, H.Q., Cui, C., Yao, J.,
022-00167-2.
30865-9. Zhang, Y., et al. (2023). An immunogenic and
3. Liu, Y., Zhang, N., Xie, C., Jiang, Y., Qin, Y.,
9. Meina, L., Wenya, Y., Feng, Y., Tao, D., and oncogenic feature-based classification for
Zhou, L., Fan, Y., Ren, L., Yin, C., Yang, H.,
Lulu, Z. (2019). Awareness of and attitudes to- chemotherapy plus PD-1 blockade in
et al. (2022). Evolution of drug regulations
ward translational medicine among health advanced esophageal squamous cell carci-
and regulatory innovation for anticancer drugs
personnel in hospitals in Shanghai, China. noma. Cancer Cell 41, 919–932.e5. https://
in China. Acta Pharm. Sin. B 12, 4365–4377.
J. Int. Med. Res. 47, 438–452. https://doi.org/ doi.org/10.1016/j.ccell.2023.03.016.
https://doi.org/10.1016/j.apsb.2022.08.004.
10.1177/0300060518809242. 14. Mai, H.Q., Chen, Q.Y., Chen, D., Hu, C., Yang,
4. Chen, C., Lou, N., Zheng, X., Wang, S., Chen,
H., and Han, X. (2021). Trends of Phase I Clin- 10. Wang, F., Wei, X.L., Wang, F.H., Xu, N., Shen, K., Wen, J., Li, J., Shi, Y., Jin, F., Xu, R., et al.
ical Trials of New Drugs in Mainland China L., Dai, G.H., Yuan, X.L., Chen, Y., Yang, S.J., (2023). Toripalimab Plus Chemotherapy for
Over the Past 10 Years (2011-2020). Front. Shi, J.H., et al. (2019). Safety, efficacy and tu- Recurrent or Metastatic Nasopharyngeal Car-
Med. 8, 777698. https://doi.org/10.3389/ mor mutational burden as a biomarker of cinoma: The JUPITER-02 Randomized Clinical
fmed.2021.777698. overall survival benefit in chemo-refractory Trial. JAMA 330, 1961–1970. https://doi.org/
5. Prasad, V., and Mailankody, S. (2017). gastric cancer treated with toripalimab, a 10.1001/jama.2023.20181.
Research and Development Spending to Bring PD-1 antibody in phase Ib/II clinical trial
15. Li, J., Qin, S., Xu, R.H., Shen, L., Xu, J., Bai,
a Single Cancer Drug to Market and Revenues NCT02915432. Ann. Oncol. 30, 1479–1486.
Y., Yang, L., Deng, Y., Chen, Z.D., Zhong,
After Approval. JAMA Intern. Med. 177, 1569– https://doi.org/10.1093/annonc/mdz197.
H., et al. (2018). Effect of Fruquintinib vs Pla-
1575. https://doi.org/10.1001/jamainternmed. 11. Wang, F.H., Wei, X.L., Feng, J., Li, Q., Xu, N., cebo on Overall Survival in Patients With Pre-
2017.3601. Hu, X.C., Liao, W., Jiang, Y., Lin, X.Y., Zhang, viously Treated Metastatic Colorectal Can-
6. Li, G., Liu, Y., Hu, H., Yuan, S., Zhou, L., and Q.Y., et al. (2021). Efficacy, Safety, and Correl- cer: The FRESCO Randomized Clinical Trial.
Chen, X. (2022). Evolution of innovative drug ative Biomarkers of Toripalimab in Previously JAMA 319, 2486–2496. https://doi.org/10.
R&D in China. Nat. Rev. Drug Discov. 21, Treated Recurrent or Metastatic Nasopharyn- 1001/jama.2018.7855.

Cell 187, March 28, 2024 1583