Almost unsurprisingly, when products can move from the laboratory to the clinic, genetic testing companies have chosen to cooperate with pharmaceutical companies to run diagnosis and treatment through, and to quickly achieve the clinical penetration of innovative diagnosis and treatment solutions in a closed-loop approach.
According to the incomplete statistics of the arterial network, since entering 2020, in clinical trials, commercialization and other links, genetic testing companies and pharmaceutical companies have cooperated more than 10 times. At the end of November, Yuewei Gene will have just been approved to list the microsatellite unstable gene detection kit (hereinafter referred to as "MSI kit") Yue iKang and its supporting instruments and analysis software authorized Chia Tai Tianqing, which has become the exclusive promoter of this product in the nationwide hospital system.
This cooperation is the first large-scale commercial cooperation of pan-cancer accompanying diagnostic reagents for tumor immuno-drugs such as PD-1/PD-L1, which represents that the overall solution for precision medicine of tumor immunology is maturing, and the rapid response of reading micro gene, which is rare in the industry, also reflects that genetic testing enterprises are maturing at the level of overall consideration of industrialization.
"As disease typing moves towards the molecular level, oncology drugs increasingly need to be involved with biomarkers in clinical applications." Chen Junjun, secretary of the board of directors of Yuewei Gene, told Arterial Network, "This is also an important reason why our cooperation with pharmaceutical companies can be hit right away. ”
The sinking need for genetic testing
The demand for genetic testing in the sinking market is being stimulated.
The first is the sudden increase in the demand for accompanying diagnostics. In recent years, biomarkers have become more closely associated with drugs, and the use of genetic testing to screen patients has become a key link before the use of innovative drugs for many major diseases. As drug development for diseases associated with a single biomarker gradually becomes saturated, pan-cancer drugs and corresponding concomitant diagnostic needs have become new growth points.
As of November 2021, the National Food and Medicines Administration (FDA) has approved three pan-cancer indications named after biomarkers, namely highly microsatellite instability/mismatch repair defect (MSI-H/dMMR) solid tumors, high tumor mutation burden (TMB-H) solid tumors, and NTRK-carrying fusion mutant solid tumors. Among them, MSI, a common clinical biomarker, has been successively written into the clinical diagnosis and treatment guidelines of more than a dozen cancer species.
The second is innovative drugs and the transformation of the accompanying diagnostic supply and demand model. Chen Qigang, head of Chia Tai Tianqing's screening and diagnosis business, pointed out, "In China, since the purchase of drugs in 2018, drug price reduction is an unstoppable trend. For example, the annual cost of tumor immunotherapy has been compressed from more than 600,000 to more than 30,000. ”
Precision medicine is a new medical concept and medical model that carries out fine classification and accurate diagnosis of diseases through diagnostic technology, so as to personalize and accurately treat diseases and specific patients, which is also the general trend of clinical treatment of tumors.
Behind the price reduction of drugs, the market for innovative drugs will sink. In the past, expensive innovative drugs often limited demand to large hospitals in large cities, and thus formed a centralized supply model along with diagnosis. With the continuous reduction of the price of drugs, the accessibility of innovative drugs continues to penetrate into primary medical institutions, and the demand for diagnosis has also sunk into the grass-roots market with scattered distribution, accelerating popularization.
In this context, the joint diagnosis and treatment has become a deeper consensus between pharmaceutical companies and genetic testing companies. "Concomitant diagnosis ultimately serves the treatment plan," Chen said, "in most scenarios, the combination of diagnosis and treatment is almost the only way." ”
Chen Qigang also pointed out that for pharmaceutical companies, the combination of tumor immunotherapy products and other drugs is a trend, the former will form a diversion for the latter, and the accompanying diagnosis of the upstream layout in advance can increase the flow of tumor drugs. In other words, behind the frequent hand-in-hand between genetic testing companies and drugs, both parties are exploring the possibility of complementary values and doing more with less than the concept of going through the whole process of diagnosis and treatment alone.
The details of the whole process are strictly controlled
In fact, the sinking market is both an opportunity and a challenge for genetic testing companies. "This means that we can no longer simply do product design based on the needs of large hospitals in first-tier cities," Chen Junjun pointed out, "In the sinking market, first of all, we must complete the equipment, followed by the use of automation means, so that doctors at different levels can get uniform, standardized interpretation results." ”
Due to the relative complexity of the technical principle itself, the fault tolerance rate of genetic testing at all stages from sample collection, data analysis to report interpretation is very low, which increases the difficulty of clinical product development and verification.
Therefore, unlike most IVD products on the market, which often appear in the form of a single product of the detection kit, the micro-gene selection from the perspective of product design to do a good job in the details of the whole process, based on the whole process of nucleic acid extraction, amplification detection, report analysis involved in the clinical pathology testing work, the MSI overall solution has been launched rarely in the industry, reducing the customer's own matching of related instruments and software links, thereby ensuring the stable output of the test results.
Image source: Courtesy of the interviewee
In China, Yuewei Gene is the first batch of teams to develop genetic testing products based on the PCR-CE platform, and the technology accumulation has exceeded 10 years. They have provided early MSI testing services for many medical institutions and enterprises, accumulated the largest amount of MSI testing in China, and are well versed in the clinical status and dilemma of PCR-CE platform and MSI testing.
"Although the installed capacity of the CE platform in China continues to grow, the total amount is still not very large, the awareness of end customers on such devices is not as deep as PCR, the clinical samples are diverse, involving a large number of control points, and CE itself is not like NGS, which can export high information with limited amounts, and the fault tolerance of downstream information analysis for upstream experiments is not high." Chen Junjun said that for MSI testing at this stage, only by providing a full-process clinical solution is enough to ensure the quality of testing.
At the same time, Yuewei Gene has established a stable technical service team and established 6 technical service centers in Xi'an, Wuhan, Guangzhou, Shanghai, Chengdu, Beijing and other cities to provide 7 * 24 hours of operation support. "In most cases, we can go to the site on the same day to help customers solve problems, which fully guarantees the high satisfaction of the client." Chen Junjun pointed out.
It is understood that the Yue Aikang, which was promoted in cooperation with Chia Tai Tianqing, took the lead in using all-single nucleotide sites in China, which is easier to interpret. MSI test results are mainly determined by identifying the crests of the locus parameters, which requires a high level of doctor experience.
MSI detection of the selected microsatellite sites have single nucleotides and double nucleotides two types, the earliest appeared in the official guidance document of the recommended site combination contains 2 single nucleotide sites, and 3 double nucleotide sites, but after repeated testing of the micro gene found that such site combination sensitivity is low, difficult to interpret, and single nucleotide sites are relatively easy to interpret, so that the operator experience dependence is less, easy to detect itself, the detection rate can be increased accordingly.
Chen Junjun explained to arterial network that choosing a new combination of sites is not an easy task, "This needs to go through the process of disassembling first and then combining." ”
In the first stage, researchers need to disassemble the clinical significance of each site, a step that can usually be supported by literature, clinical data, etc. Subsequently, the clinical significance of each site needs to be verified experimentally. "This is very challenging," Chen Junjun said, "because the clinical value of the fork site in various interference factors, sample types, and degradation states is very demanding on technical strength." "The second stage is the combined verification of the sites, which means repeated testing and adjustment," so in the process of kit development, we need to do repeated research, continuously optimize the equipment and software, and finally determine the product form. ”
How is 1+1 greater than 2?
"Clinical awareness of MSI testing is slowly becoming clear, and many hospitals have begun to do it." Chen Qigang pointed out. In his view, the clinical cognitive process of this MSI detection can be divided into two dimensions, the first is the recognition of MSI detection technology and the project itself, including clinical benefits, operational requirements, etc. After years of application and promotion, the clinical cognition of this dimension has been relatively mature, and almost all pathologists in China understand MSI detection. However, clinical awareness needs to be strengthened in the correlation verification dimensions of MSI detection and tumor immunotherapy, which is why MSI testing needs to be coordinated with pharmaceutical resources." ”
Specifically, in the cooperative promotion, pharmaceutical companies and genetic testing companies can open up the academic promotion capabilities of both sides. Among them, pharmaceutical companies have a strong academic promotion and control of clinical dynamics, which is exactly what genetic testing companies lack, which will cause information asymmetry and lead to missing the key needs of follow-up research and development. "Pharmaceutical companies are faced with the academic needs of the 'diagnosis and treatment system' proposed by the clinic, and usually do not have the technical and knowledge reserves of 'diagnosis'." Chen Qigang pointed out, "But this is exactly what genetic testing companies are good at." Therefore, the cooperation between the two sides is essentially the deep integration of the Know How process of the pharmaceutical company and the Know How process of the genetic testing company. ”
As a gene technology enterprise with many years of deep cultivation, Yuewei Gene has formed industry-leading capabilities in data mining and product transformation, "With the deepening of research, we have found more and more that only by combining our own gene technology capabilities with richer clinical samples and clinical data can we achieve the best transformation." Chen Junjun pointed out, "Therefore, cooperation with large pharmaceutical companies with rich medical resources such as Chia Tai Tianqing is a very critical step in the development process of Yuewei Gene." ”
GMP Lab (Source: Courtesy of respondent)
Admittedly, major advances in the industry often come from information asymmetries being broken. However, the cooperation between genetic testing companies and pharmaceutical companies, if you want to enter the ideal state, there are many control elements in advance and in the event. "We are constantly exploring and summarizing." Chen Qigang said.
The first is that the genetic testing company's own products must be excellent. In addition to relatively more "obvious" elements such as technological innovation, product design, and process transformation, production verification and quality control must also be in place. Taking Yuewei Gene as an example, in addition to the GMP-level clean production environment, the company has established a complete quality control system from raw materials to outbound products to strictly control product quality.
The second is the product pipeline of pharmaceutical companies, which can work well with genetic testing products. This synergy is reflected in all stages of product development, product registration, academic promotion and other stages of the productization of genetic testing technologies. For example, the complete clinical trial samples and data of pharmaceutical companies, the improvement of the registration system and the standardized management can help the genetic testing companies to obtain relatively smooth approval of accompanying diagnostic products. For another example, with the help of the academic promotion ability of pharmaceutical companies in the corresponding indications, the professional academic knowledge involved in genetic testing products can be accurately and comprehensively transmitted to clinical users, and while establishing good user relations, combing their own brands.
Finally, there is precise control of the details of cooperation, including the stability of the team, the clear agreement on the rights and obligations of both parties, and the conditions and nodes for the delivery of products and services. Chen Qigang pointed out that at present, pharmaceutical companies usually establish a special accompanying diagnostic business team, which requires both sides to maintain efficient and stable docking and jointly promote cooperation.
Chen Junjun stressed that the cooperation between Yuewei Gene and Chia Tai Tianqing's MSI reagent is only the starting point of strategic cooperation, and the two sides will carry out in-depth cooperation in data mining, product transformation, production quality control and other aspects in the field of genes in the future.
For example, in the patient recruitment process of new drug clinical trials, genetic testing companies can screen target groups through patient genome data to accelerate the process of clinical trials of pharmaceutical companies. According to statistics, after the inclusion of patient genomic data, the overall clinical trial success rate from Phase I clinical trial to drug approval is much higher than that of unused situations.
As the application of gene technology in the clinic continues to advance in depth, many diseases that were previously considered incurable have effective solutions, and drugs that were previously considered ineffective may also save some patients in specific situations. When this new technology is applied in a wider area, it is undoubtedly inseparable from the energy efficiency amplification brought about by the superposition of resources, and we look forward to genetic testing and pharmaceutical companies to spark in more dimensions.
*Cover Source: 123rf