January 29, 2020，Eli Lilly recently announced that the US Food and Drug Administration (FDA) has accepted new drug applications (NDA) for selpercatinib (LOXO-292) and granted priority review. That the drug is an oral RET kinase inhibitor used to treat patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC), RET mutant medullary thyroid carcinoma (MTC), and RET fusion-positive thyroid cancer. The FDA has designated the NDA's prescription drug user fee method (PDUFA) target date to be the third quarter of 2020.

Selpercatinib (LOXO-292) is a potent, oral, highly selective transfection rearrangement (RET) kinase inhibitor for the treatment of cancer patients with abnormal RET. The RET gene is a proto-oncogene that undergoes rearrangement during transfection, and hence its name. This gene encodes a cell membrane receptor tyrosine kinase, and its abnormality is a rare driver of many types of tumors.

This NDA is based on data from Phase I / II clinical study LIBRETTO-001. The study is the largest clinical study evaluating one kind RET inhibitor to treat RET altered cancer patients. The results showed that the ORR of selpercatinib in patients with RET-mutated medullary thyroid carcinoma (MTC) who had not previously received treatment (initial treatment) and had previously received treatment (treatment) were 59% and 56%, respectively. Previously published data on the NSCLC cohort showed that the ORR of selpercatinib in newly-treated and treated RET fusion-positive NSCLC patients were 85% and 68%, respectively; in addition, selpercatinib was the first RET that showed strong central nervous system (CNS) activity Inhibitor, CNS ORR is as high as 91%.

It is estimated that RET fusion exists in about 2% of non-small cell lung cancer (NSCLC), 10-20% of papillary thyroid cancer (PTC) and other types of thyroid cancer, and other cancers (such as colorectal cancer) subgroups; RET point mutations are present in approximately 60% of medullary thyroid carcinoma (MTC). RET fusion and RET point mutation cancers mainly rely on the activation of RET kinase to maintain their proliferation and survival. This dependence is often called "oncogene addiction", making these tumors highly sensitive to small molecule inhibitors targeting RET.

Selpercatinib is designed to inhibit natural RET signal transduction and the expected acquired drug resistance mechanism. The drug is currently in clinical development for patients with abnormal RET kinase in tumors.

In the United States, the FDA has granted selpercatinib a breakthrough drug qualification (BTD) for the treatment of three types of patients, specifically: (1) Patients with metastatic RET fusion-positive NSCLC who progressed after receiving platinum-containing chemotherapy and a PD-1 or PD-L1 tumor immunotherapy treatment and required systemic therapy (systemic therapy); (2) Patients with RET mutant medullary thyroid carcinoma (MTC) who have undergone prior treatment and have no acceptable alternative treatment options and require systematic treatment; (3 ) Patients with advanced RET fusion-positive thyroid cancer who have progressed after receiving other programs and have no acceptable alternative treatment programs and require systemic treatment.

In 2019, the FDA granted selpercatinib orphan drug status for the treatment of: RET fusion-positive NSCLC, RET fusion-positive, and RET mutant thyroid cancer, including poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, MTC, locally advanced or metastatic follicular or papillary thyroid cancer.

In December 2019, Lilly launched two phase III trials of selpercatinib: the LIBRETTO-431 trial was used to treat patients with newly treated RET fusion positive NSCLC, and LIBRETTO-531 was used to treat patients with newly treated RET mutation MTC. Each trial will recruit 400 patients.

Source: Lilly Receives FDA Priority Review for the Selpercatinib New Drug Application

Article link: http://news.bioon.com/article/6749731.html

February 23, 2020，Chugai, a Japanese pharmaceutical company controlled by Roche, recently announced that the Ministry of Health, Labor and Welfare (MHLW) has approved the targeted anticancer drug Alecensa（alectinib）150mg capsules a new indication for the treatment of relapsed or refractory ALK fusion gene positive anaplastic large cell lymphoma (ALK + ALCL). Previously, MHLW had granted Alecensa the orphan drug qualification for this indication.

The common treatment for ALCL is chemotherapy. However, for patients with ALCL who relapse after chemotherapy, there is no standard treatment, so the demand for new effective drugs is increasing. The approval of Alecensa's new indication will provide a new and important treatment option for patients with relapsed or refractory ALK + ALCL.

This approval is based on data from the ALC-ALCL study. This is a multi-center phase II study started in 2015 to evaluate the efficacy and safety of Alecensa in patients with relapsed or refractory ALK + ALCL. A total of 10 patients were enrolled in the study. The results showed that the overall remission rate (ORR) of Alecensa treatment was 80.0% (bilateral 90% CI: 56.15-95.91%). The incidence of adverse reactions was 100%. The most common adverse reactions included: maculopapular rash (40.0%, 4/10 cases), and upper respiratory tract infections, bronchitis, and increased blood alkaline phosphatase (30.0% each, 3/10 cases) ).

ALCL is a non-Hodgkin's lymphoma that originates from T cells in lymphocytes. It is one of the four subtypes of peripheral T cell lymphoma and belongs to malignant lymphoma. The degree of malignancy is classified as "moderate", and the disease progression needs to be observed monthly. In Japan, the proportion of ALCL in malignant lymphoma is 1.5% -2.0%, about half of which are reported as ALK positive. Considering the data from a global study, the 5-year survival rate of successful ALK + ALCL patients receiving chemotherapy is 60%, so relapsed and refractory cases are estimated to account for 40%.

Alecensa is a new small molecule tyrosine kinase inhibitor (TKI) that targets ALK, can cross the blood-brain barrier, and has strong efficacy against brain metastases. The drug has been approved: (1) Single-agent second-line treatment Patients with ALK-positive NSCLC who have received Xalkori (crizotinib) progression in the past; (2) single-agent first-line treatment of ALK-positive NSCLC patients; (3) single-agent treatment of patients with relapsed or refractory ALK-positive ALCL

It is worth mentioning that, in the National Comprehensive Cancer Network (NCCN) guidelines, in the treatment of ALK-positive metastatic NSCLC, Alecensa is the only first-line treatment plan (preferred) (Class 1).

In China, Alecensa was approved in August 2018 as a monotherapy for the treatment of patients with ALK-positive NSCLC. Lung cancer is the most common type of cancer and the leading cause of cancer death. NSCLC is the most common type of lung cancer, and ALK-positive NSCLC is a unique type, commonly seen in younger (median age 52 years) lung cancer populations with no history of smoking, especially in a specific type of NSCLC population called adenocarcinoma，approximately 5% of NSCLC are ALK positive.

Source of the original text: Chugai Obtains approval for Additional Indication of Alecensa for Recurrent or Refractory ALK Fusion Gene-Positive Anaplastic Large Cell Lymphoma

Article link: http://news.bioon.com/article/6750940.html

Introduction

In 2018, Huawei Cloud launched the world's first gene container service GCS (GeneContainer Service), which makes the calculation of gene sequencing data more economical, faster, and easier. After using GCS, it achieved the goal of reducing the efficiency of sequencing operation cycle.

In recent years, gene sequencing technology has been widely used in basic research and clinical applications. With the continuous development of technology and the continuous standardization of the sequencing market, China's gene sequencing market has grown significantly and entered a period of rapid development, which has become a global one of the strongholds of the NGS (next-generation sequencing) market. From 2007 to 2017, the market growth rate of the Chinese gene sequencing industry was higher than the global level, with an average annual compound growth rate of 47.5%; in 2017, the market size exceeded 7 billion yuan. According to the China Business Research Institute, this figure will exceed 15 billion yuan in 2022. As the technology used in gene sequencing matures, the next decade will be the "golden decade" in which the genome business model matures.

With the continuous integration of big data and life sciences, the life science industry is undergoing drastic changes, "precision medicine" becomes a reality, the processing of massive data generated by gene sequencing has become a new challenge, and it is imperative to gradually go to the cloud to become an era of digital life. Initiatives.

Understanding the pain point of gene industry, calculation is the key

At present, the focus of gene sequencing work has shifted from sequence reading to data processing, and the analysis and interpretation of genetic data is a key link related to the development of gene sequencing and precision medical applications. However, the current data analysis of gene sequencing also has many difficulties, such as: the inability to elastically match the computing power, the difficulty of improving the operating efficiency of the host, and the difficulty of achieving the sharing of massive data storage, etc., which have hindered the development of clinical applications to a certain extent.

The amount of genetic data continues to expand, and a large amount of data is scattered in different countries, cities, and hospitals, and lacks uniformity. Such scattered and free data is not conducive to precision medical research under the guidance of big data. Data integration and sharing is a difficulty that hinders the clinical transformation of gene sequencing data.

The current data lacks standardization. In many cases, even in the same hospital, due to different biological sequencing equipment, software and even processes, the data format will be very different. "When we put this data together, there will be systematic deviations." Industry practitioners said, "Standardization refers not only to molecular data, but also includes individual patient information, medication, and follow-up after recovery. These data information The unification and a certain degree of sharing need to be resolved. "

At this stage, the application of gene sequencing is still mainly concentrated in the two fields of non-invasive prenatal detection and tumor diagnosis and treatment. It has not been widely used in clinical practice. With the wider application, it has higher intensive computing and massive data processing capabilities. Claim.

Cloud computing is a powerful tool to solve the pain points of the genetic testing industry. With the advent of the 5G era, cloud computing will bring more possibilities to the gene sequencing industry while ensuring the calculation, storage and analysis of massive data.

What role does cloud technology play in the gene sequencing industry?

In the field of genetic testing, data analysis and processing of collected genetic samples requires a large amount of computing resources. Gene sequencing companies require huge amounts of computing power; life sciences research competitions have often become a competition in computing power. Large scientific achievements are usually based on huge data. Current medical tests such as prenatal testing and tumor testing also consume a lot of computing power. The demand for computing power of these gene sequencing is fluctuating. Often, Q4 consumes the most and Q1  consumes has the least. At the same time, the computing power required for the genomes of different organisms is also different. This will involve the expansion and contraction of the computing cluster. The traditional Offline computing clusters cannot be scaled up or down quickly. This is the convenience of using cloud computing.

For the gene sequencing industry, Huawei Cloud has customized a variety of highly integrated gene sequencing solutions for customers. Compared with the HPC high-performance computing cluster traditionally used in the industry, the gene container service has obvious advantages: resource scheduling is more flexible, computing can be scaled as needed, task flow is easy to customize, and containers are easier to maintain and upgrade.

Cloud computing helps rapid development of gene sequencing and technological innovation

Through the cooperation case between Huawei Cloud and BGI, we can clearly see that Huawei Cloud can reduce the operating cycle, improve the calculation efficiency and data storage capacity, shorten the reporting cycle, and ensure the calculation, storage and analysis of massive data. The gene sequencing industry is more likely to plug new wings into the gene sequencing industry, maximize the computing power, enable faster and more biological information analysis, expand application fields, and help the development of precision medicine.

For the gene sequencing industry, it has the best development opportunities, but it also faces huge challenges. This challenge is how to achieve faster sequencing, faster analysis, and more importantly, faster technological innovation. By combining cloud technology, New technologies such as artificial intelligence and 5G will bring new impetus to the industry. Only in this way can the company stand out from the competition, and the entire industry can adapt to the development speed of precision medicine, and benefit the future with technology.

Link: http://www.genegood.cn/a/news/101.html

In 2015, QIAGEN announced the official launch of the commercialization of the fully automated next-generation sequencing platform GeneReader NGS System, and launched the first complete next-generation sequencing (NGS) automation platform from sample preparation to data interpretation to accommodate  needs of different laboratories. Recently, QIAGEN announced that it had stopped the development of its next-generation sequencing platform GeneReader and established a long-term cooperation with illumina to develop next-generation sequencing IVD detection products.

On October 7, local time, QIAGEN announced a new direction for its NGS-related business: to establish a 15-year partnership with illumina to further expand the IVD test kit based on NGS technology in patient management (including concomitant diagnosis) application. At the same time, QIAGEN also lowered the company's third-quarter sales growth forecast, and announced that its CEO Peer Schatz will leave after 27 years of service and switch to the company's special consultant position.

Under the terms of this latest non-exclusive agreement, QIAGEN will have the right to develop and commercialize IVD kits for illumina's MiSeq Dx and NextSeq 550Dx systems. The agreement also granted QIAGEN the right to expand cooperation on illumina's future clinical diagnostic system. The partnership will also provide opportunities for QIAGEN to develop and promote illumina-based TruSight Oncology analysis methods in the future. Based on this cooperation, the two parties will first focus on tumor-related IVD kits to the market to support patient management. In the future, the cooperation may expand to more clinical diagnostic fields, such as cardiology, genetic diseases, infectious diseases, and inflammation and autoimmune diseases.

Francis deSouza, CEO of illumina, said: "We are committed to increasing clinical use cases resolved through genome sequencing to enable partners to provide IVD testing and concomitant diagnosis on illumina's Dx instruments. Our cooperation with QIAGEN will provide illumina's TSO 500 series provides more detection menu options, thereby accelerating the application of NGS in the management of cancer patients. "

"Our strong cooperation is an important milestone, marking the advancement of the use of NGS technology in clinical decision-making and our shared vision to use this powerful technology to improve the clinical outcomes of patients worldwide," QIAGEN CEO Peer Schatz say. "QIAGEN is very pleased with this groundbreaking partnership and hopes that this relationship can leverage our unique strengths and develop into a long-term and productive partnership. This partnership is a key step in our NGS strategy. The strategy will continue to include universal solutions for any sequencer, as well as the GeneReader NGS system, which is mainly suitable for smaller targeted gene kits. Through this partnership, we look forward to creating significant benefits for customers and both parties and letting QIAGEN to maximize the opportunities for us to create value as a company by providing solutions from sample preparation to data interpretation. "

Although the parties did not disclose the financial terms of the agreement, Tycho Peterson, an analyst from JPMorgan Chase, said in an analysis report that QIAGEN may pay illumina a platform access fee and achieve certain development, regulatory and commercialization milestones related payments. In addition, as part of restructuring of QIAGEN , the company will bear pre-tax restructuring costs of approximately US $ 260 million to US $ 265 million. About 75% of it, namely US $ 195 million to US $ 200 million, will be used to terminate non-cash projects related to NGS instrument development activities. According to QIAGEN, these are related to "software and tool development, licensing, partner company valuation, and other asset impairments."

In addition, it is unclear what impact the termination of GeneReader system development will have on the agreement between QIAGEN and Natera in 2018 to develop cfDNA prenatal screening methods based on GeneReader, but QIAGEN said it would discuss with Natera "how to continue relationship". QIAGEN company spokesman Thomas Theuringer also said that due to the stop of GeneReader system development, the number of layoffs has not been made public, although the company plans to create new job opportunities in other fields. But all locations involved in the development of NGS instruments will be affected, including QIAGEN ’s German headquarters and R & D center in Massachusetts.

In 2012, QIAGEN mastered the basic technology of its fully automated next-generation sequencing system GeneReader by acquiring Intelligent Biosystems (IBS). Since the instrument was released in 2015,QIAGEN has been committed to promoting and selling GeneReade. But the commercialization of the system is not going well. Illumina sued QIAGEN in 2016, claiming that the system violated its intellectual property rights. The lawsuit resulted in a US ban, which in turn stopped QIAGEN from selling all GeneReader systems in the United States. The lawsuit was settled in 2017, and QIAGEN used a new chemical to resume sales of GeneReader in the United States. For the Chinese market, in 2017, QIAGEN also co-founded a joint venture company,MAQGEN, with China ’s IVD industry leader Maccura Biology, to help introduce the GeneReader NGS system to the Chinese clinical and scientific research market, and to help realize the localization of QIAGEN gene sequencing products in China Change. So far, the adoption rate of the product is still low, with revenues in 2018 of no more than US $ 10 million to US $ 15 million. As early as July, QIAGEN announced that it would reorganize its Chinese joint venture because China's adoption of in vitro diagnostic technology was lower than expected. Some analysts said after the agreement was released that it may be a wise decision to suspend the development of GeneReader.

Jonathan Arnold, vice president and head of oncology and precision diagnosis of QIAGEN, said after the latest agreement was announced that the company will continue to provide "indefinite" support for current GeneReader customers, and the company will still sell the instrument. He also mentioned that GeneReader has created a good market for proprietary needs. "The continuing need for targeted sequencing still exists, so we still think it's very important to support our customers and the platform." But he added, "This platform is a RUO system and will never become an IVD system."

For future cooperation with illumina, QIAGEN spokesman Thomas Theuringer said that the release time of the new NGS Panel will depend on the regulatory approval process, but the first batch of products may be put on the market in 2022 or 2023. In addition, this partnership will bring illumina access to routine diagnostic laboratories and contribute to QIAGEN’s front-end sample preparation technology and back-end bioinformatics expertise, which will greatly benefit illumina and will further strengthen the leading position of illumina  in the field of next-generation sequencing. According to Thomas Theuringer, QIAGEN ’s current primary goal is to develop testing products for its pharmaceutical company partners and envision two types of pharmaceutical trading projects: one is to customize NGS Panel for specific clinical projects; the other is The project is a comprehensive cancer comprehensive analysis, "This will begin to move towards what I think is a general-purpose companion diagnostic method." It is reported that QIAGEN has started a dialogue with potential pharmaceutical partners on NGS detection methods.

In the long run, reducing the loss of its GeneReader and turning to higher-growth technology should help QIAGEN, but it may be difficult to control in the near future. The company's third-quarter sales increased by 3% and failed to meet its 4% to 5% growth target. The company blamed the decline on China's slowdown in growth. But the company said that its overall revenue will be within expectations.

At the same time as business restructuring in the NGS field,QIAGEN also plans to reallocate some resources. For example, the company plans to expand its activities in the QIAGEN business service centers in Poland and the Philippines. Thomas Theuringer said: "Our business is very concentrated. Now, we are working hard to move the operation closer to the business in response to our customers." Therefore, he added that the entire resource will be renewed globally distribution.

Reference materials:

1、QIAGEN Partners With Illumina on NGS IVD Kits; CEO Departing; Preliminary Q3 Revenue Growth Lowered

2、QIAGEN Nixes Sequencer Development, Sees New NGS Opportunities With Illumina Deal

3、Illumina and QIAGEN Partner to Deliver Sequencing-Based In-Vitro Diagnostic (IVD) Tests

Link: https://www.sohu.com/a/346142578_733985