Before the exclusive interview with the first financial reporter, Wang Jinhu had just received a consultation from a mother of a child.
Wang Jinhu is the deputy director of the Hematology and Oncology Center at the Children's Hospital Affiliated to Zhejiang University School of Medicine, and the mother is looking for relief for her tumor-stricken child.
The larottinib inhibitor needed by this patient has not yet been approved in China.
Recently, affected by the epidemic in Hong Kong, the only channel for purchasing medicines has been blocked.
After taking off-label medication for 23 days, the child's tumor shrank significantly, but now the mother is in trouble due to problems with dosage forms and drug purchase channels.
In Wang Jinhu's view, this situation is not uncommon in the field of children's oncology.
Malignant tumors have become the second leading cause of death in children.
Compared with adult tumors, pediatric tumors are more diverse and more complex.
At present, there is a serious shortage of children's oncology drugs, and due to the difficulty and long period of clinical research, the development of related drugs faces multiple challenges.
Lack of targeted drugs
How many types of malignant tumors are there in children?
Yuan Xiaojun, chief physician of the Department of Pediatric Hematology and Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, mentioned dozens of types, including common leukemia, lymphoma, neuroblastoma, etc.
In 2019, the authoritative medical journal "The Lancet Oncology" released the first report assessing the global disease burden of childhood and adolescent cancers. 6th largest cancer burden.
The situation in China is not optimistic.
The regions with the highest global childhood cancer burden in 2017 were Asia and Oceania.
India has the highest burden of childhood cancer, and China ranks second globally.
There are 30,000-40,000 children with cancer in China every year, but there is no consensus on this public data, and there are too many children who have not been diagnosed and counted.
On the type distribution of childhood tumors, Yuan Xiaojun shared a set of data: leukemia accounts for more than 30% of childhood tumors, brain tumors account for about 20%, and neuroblastoma accounts for 7%-8%.
The causes of children's tumors are different from those of adults. Most children's tumors are more sensitive to traditional chemotherapy drugs. Combined with surgery, radiotherapy and other treatment methods, the overall prognosis of children's tumors is better than that of adults.
However, treatment effects vary widely between countries.
Judging from the cure rate, the cure rate of childhood tumors in developed countries in Europe and the United States has reached 80%, and the cure rate in resource-poor regions such as Africa and India is only 20%.
"The cure rate of childhood tumors in China is increasing year by year. The current overall treatment status and treatment situation of childhood tumors in China are at the middle level in the world. The cure rate of some tumors is very close to the international advanced level, but there are still about 20%-30% of childhood malignant tumors. However, conventional treatments are not very effective, and even with all current conventional treatments such as chemotherapy, surgery, and radiotherapy, the lives of these children cannot be saved, so targeted drugs are urgently needed to help.”
Yuan Xiaojun used the neuroblastoma known as the "King of Childhood Cancer" as an example. The long-term survival rate of low-risk patients is over 90%, and some patients with stage IVs can recover without treatment, but the long-term survival rate of high-risk patients is less than 30%.
In reality, when more than 70% of children with neuroblastoma go to the doctor, the tumor is already in stage III or IV, which is a "late stage" tumor.
She believes that the main reason for the large gap between the overall treatment level of neuroblastoma in China and abroad is the lack of targeted drugs to treat this cancer king.
Fortunately, from 2022, Chinese children with neuroblastoma have been able to use special targeted drugs, but the development of drugs for other high-risk and recurrent childhood tumors is still imminent.
"Surgery alone cannot solve all problems. In many cases, tumor drugs may be more important than surgery. Some researchers have found that children's tumors have their own driving mechanisms, and the overlap rate of mutation genes driven by adult tumors is very low, so many targeted Targeted drugs and small-molecule drugs discovered by adult targets cannot be directly applied to children." Wang Jinhu once mentioned.
At present, there are three pediatric oncology drugs used in the Boao Lecheng Pioneer Zone in Hainan. Datuximab β has been approved for marketing in 2021, selumetinib is used for neurofibromatosis type 1, and nasituximab is used for the treatment of neurofibromatosis type 1. Children 1 year and older and adults with relapsed or refractory bone marrow high-risk neuroblastoma.
The GD2 monoclonal antibody introduced by BeiGene has also passed the research in the Boao Lecheng Pilot Zone, and was finally approved for clinical application.
According to the data from Wisdom Buds, there are about 3,300 patents related to children's oncology drugs in the world, and the United States has the highest technology intensity.
In recent years, China's R&D has grown rapidly, ranking second.
Where does business power come from?
Pharmaceutical companies often lack commercial incentives to develop children's oncology drugs.
The number of children's drug research is small, mainly because the number of mutations in children's tumors is much less than that in adults, which is more costly and time-consuming in research and development.
Clinical research on children's drugs in the United States generally takes 8 to 14 years to produce results, and the ultra-long period puts great pressure on enterprises.
Even global big pharmaceutical companies such as Novartis will be discouraged.
"Research on children's tumors is seriously insufficient. In the past 30 years, the new drugs developed for children's tumors in the world are only single digits. GD2 antibody is a very rare example." Li Zhizhong, secretary general of Shiyu Children's Public Welfare Foundation, in a speech in 2021 Said: "I worked at Novartis for a few years. I once wanted to make a children's oncology drug, but was quickly rejected by the boss, saying that this has no market value."
The GD2 antibody mentioned in Li Zhizhong is a specific drug for the treatment of neuroblastoma.
At the end of 2020, the pharmaceutical company Y-mAbs Therapeutics' monoclonal antibody targeting GD2 was approved by the FDA, becoming the third GD2 antibody drug approved in the world.
Y-mAbs Therapeutics is a small company founded in 2015.
"Many drugs are considered to have no market value in the early stages of development, until a small company makes it and is bought by a large company at a price of billions." Li Zhizhong said: "So, whether there is a market value depends purely on whether it is done or not. It has market value when it is made.”
In 2021, domestic pharmaceutical company BeiGene introduced GD2 mAb.
You must know that BeiGene has not been in the field of children's oncology for a long time. Due to the uncertain commercialization prospects, the introduction of this drug once caused controversy within the company.
"We have just begun to enter the field of children's oncology. First, we found that there was a demand, and then we realized the introduction of GD2 monoclonal antibody. The process of introduction was not so smooth." Liu Yan, vice president of BeiGene, said in an interview with China Business News. : "After all, as a commercial company, from the point of view of profit, the introduction of such drugs is indeed not to make money."
At present, in the field of children's oncology, BeiGene has two related products, one is GD2 monoclonal antibody and the other is CD3-CD19 bispecific antibody for the treatment of acute lymphoblastic leukemia.
In recent years, China has issued a number of guidelines and has begun to pay attention to the research and development of children's oncology drugs. However, due to the lack of specific incentives, companies are still lacking in the research and development of children's oncology drugs, and relevant clinical trials are even less.
In Wang Jinhu's view, clinical trials of children's oncology drugs need to take into account more complex contents, including ethics and informed consent, oral drug dosage forms, etc.
For example, adult capsule preparations cannot be swallowed by children aged 1-2 years, and new dosage forms need to be developed, which increases the cost.
Therefore, in the actual operation of clinical trials, due to the particularity of the age of the child population, the expected efficiency of the enterprise may be affected.
The beginning of domestic pharmaceutical companies
"Policies have not yet directly helped pharmaceutical companies. If companies develop new drugs for children's tumors, there is no clear path on how to improve efficiency and reduce costs." Li Zhizhong commented.
Some countries have begun to encourage refractory or relapsed childhood cancer patients to participate in clinical trials.
Wang Jinhu told Yicai.com that if there are multiple drugs from multiple pharmaceutical companies expanding children's indications or developing new drugs for children on the platform of the Clinical Medical Center, children will have more opportunities to participate in clinical trials of new drugs.
Assuming that the positive rate of a target in children's tumors is 1%, there are 20 drugs in clinical trials, and children have a 20% chance of participating in clinical trials of new drugs.
He believes that China also needs more large-scale and high-level research centers as platforms to cooperate with pharmaceutical companies and R&D units.
In this way, patients are more concentrated, which can improve the efficiency of clinical trials and reduce the difficulty of operation.
Of course, the establishment of a relatively mature platform for pediatric clinical trials needs to be guided by active policies.
"Drugs can enter clinical trials, of course, success is very good, even if they are unsuccessful, they will leave very important data, which will lay the foundation for future children's recovery and future children's growth." Li Zhizhong said.
Based on the difficulty of children's clinical research, the use of real-world data, that is, related diagnosis and treatment data, to supplement research on children's oncology drugs is expected to shorten the drug development cycle.
Gao Ying, senior medical director of Zerokrypton Technology, believes that the process of generating real world evidence (RWE) from real world data (RWD) is conducive to the development of children's oncology drugs and helps improve the efficiency of research and development, including positive changes in research cycle and research costs.
"The biggest difficulty lies in the quality of real-world data. To maximize the value of existing data, it is necessary to transform medical-level data into research-level data through data governance."
In recent years, many domestic pharmaceutical companies have begun to try to develop in the field of children's oncology.
Junshi Bio, Betta Pharmaceuticals, Chia Tai Tianqing, Hengrui Pharmaceuticals, Qilu Pharmaceuticals, Fosun Pharmaceuticals, etc. are all actively involved.
Wang Jinhu said that in addition to traditional large pharmaceutical companies, there are many emerging small and medium-sized pharmaceutical companies in China that have begun to pay attention to and invest in the development of children's oncology drugs.
"Either introduction or transformation, more and more work is being carried out. With the efforts of many parties, China will gradually form a good research and development atmosphere, and finally realize that the corresponding problems will be found, and corresponding drugs will be available."