Fosun Pharma's Half-Year R&D Investment Nears RMB 1.2 Billion as Its CAR-T Candidate FKC876 Poised to Become China’s First Approved Therapy

Recently, Fosun Pharma announced in a public notice that itsInvestment CompanyFosun Kite's CAR-T Product FKC876 Officially Receives Approval from the National Medical Products AdministrationClinical TrialApproved. The product is poised to become the first CAR-T cell therapy approved for marketing in China. In the first half of 2018, Fosun Pharma’s R&D investment reached RMB 1.188 billion, surpassing that of Hengrui Medicine. Five biologic drugs were in Phase III clinical trials, and a marketing application for rituximab was submitted, with approval imminent. During the reporting period, three blockbuster products from the company passed the consistency evaluation, and ten products were in the application stage, marking progress that outpaced most pharmaceutical enterprises.

On August 28, Fosun Pharma released its 2018 semi-annual report. The company achieved operating revenue of RMB 11.859 billion, representing a year-on-year increase of 41.97%. Net profit attributable to shareholders of the listed company amounted to RMB 1.561 billion, a year-on-year decrease of 7.61%. One of the primary reasons for the decline in net profit attributable to shareholders was the increased investment in innovative research and development and business layout.

During the reporting period, the Company’s R&D investment amounted to RMB 1.188 billion, representing a year-on-year increase of 89.82% compared to the same period last year. R&D expenses totaled RMB 709 million, a year-on-year increase of 53.69%. The pharmaceutical manufacturing and R&D business segment serves as both the cornerstone of the Company’s performance and the primary focus of its R&D investment. In the first half of 2018, the Company’s R&D investment in this segment reached RMB 1.064 billion, a year-on-year increase of 100.9%, while R&D expenses amounted to RMB 596 million, a year-on-year increase of 63.29%.

China’s First CAR-T Race: Fosun Pharma Overtakes as the Latecomer

CAR-T, or chimeric antigen receptor T-cell immunotherapy, is currentlyLeukemia, lymphoma,Melanoma, has demonstrated favorable anti- in the treatment of malignant tumors such as gliomasTumorEffect.Novartis, Kite and other companies are at the forefront of CAR-T product development. China has also seized this trend, leading to rapid advancements in CAR-T research and development within the country.

From the current progress of CAR-T product development by domestic pharmaceutical companies in China, CBio, PersonGen, Healikang, and Nanjing Legend are at the forefront. Since 2015, companies such as Galaxy Bio, Carsgen Therapeutics, and Hengrui Medicine have also made significant investments in CAR-T products, achieving varying degrees of progress.

According to data from Menet’s Global Drug R&D Database, Cytopeutics’ leading CAR-T products, including CBM-C30.1, CBM-C19.1, and CBM-EGFR.1, are all in Phase II clinical trials. BoShengJi’s CAR-T products, such as PCAR-019, anti-MUC1 CAR T-cell therapy, and CAR-pNK, are also in Phase II clinical trials. Meanwhile, emerging player CARsgen Therapeutics’ CAR-T products, including CSG-EGFR and CSG-CD19, are currently in Phase I clinical trials.

It can be seen that Fosun Pharma’s layout in CAR-T products was not early, but the company caught up rapidly through cooperation with Kite Pharma. In early 2017, the company established a joint venture, Fosun Kite Biotechnology Co., Ltd., with Kite Pharma, officially commencing the research and development of CAR-T products. On September 6, 2018, Fosun Pharma announced that Fosun Kite’s CAR-T product FKC876 had officially received approval from the National Medical Products Administration.Clinical TrialApproved.

FKC876, marketed in the United States under the brand name Yescarta, was approved by the U.S. FDA for market launch on October 18, 2017, and isFDAThe first approved CAR-T cell therapy for specific non-Hodgkin lymphoma. On August 27, 2018, Yescarta received marketing authorization from the European Medicines Agency (EMA), becoming one of the first CAR-T cell therapies launched in Europe for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL).

According to data from the Menet MED China Drug Evaluation Database 2.0, the clinical trial application for Fosun Kite’s FKC876 in the treatment of relapsed or refractory large B-cell lymphoma was accepted by the Center for Drug Evaluation (CDE) on May 18, 2018, under acceptance number CXSL1800059. The technical review was completed within just 98 days (fewer than 70 working days) from the date of formal acceptance by the CDE. This demonstrates the significant effectiveness of national efforts to optimize drug evaluation and approval reforms, and also reflects the CDE’s recognition and affirmation of the quality of the company’s submission materials.

Previously, Yang Sheng, Deputy Director of the Drug Registration Department of the National Medical Products Administration (NMPA), pointed out: “For drugs already marketed overseas that treat severe, life-threatening diseases with no effective therapeutic options, as well as rare diseases, and where research has confirmed the absence of ethnic differences, applicants are exempt from submitting clinical trial applications and may directly seek marketing approval using overseas clinical trial data. This will accelerate the drug’s market launch by 1–2 years.” Fosun Kite Biotechnology Co., Ltd. has directly introduced products that have completed clinical trials and achieved mature market approval in the United States and the European Union. With its clinical trial application now approved, the company is poised to leverage overseas data to expedite domestic development.Clinical Trials, In theory, as long as it can be proven that there are no racial differences, Fosun Kite Biotechnology Co., Ltd. could directly apply for market approval using overseas clinical trial data, achieving a leapfrog advancement in progress and potentially "securing" the first CAR-T product in China.

According to the Menet Global Drug R&D Database, in addition to Kite’s Yescarta, other CAR-T products currently marketed globally includeNovartisThe pharmaceutical product tisagenlecleucel-T (brand name Kymriah) and Fosun Kite’s FKC876 both target CD19. They are primarily used to treat acute lymphoblastic leukemia in children and young adults (aged 2–25 years) and relapsed or refractory large B-cell lymphoma in adults.

Betting on Monoclonal Antibody Biologics: Rituximab Launch Imminent

According to the annual and interim reports of Fosun Pharma, the company’s R&D expenditure amounted to RMB 1.529 billion for the full year 2017. In the first half of 2018 alone, R&D spending reached RMB 1.188 billion, nearly approaching the total R&D investment of the previous year. The company’s R&D portfolio focuses on innovative biologics such as monoclonal antibodies, biosimilars, and innovative small-molecule drugs.

According to the interim report data of Fosun Pharma, during the reporting period, the company further accelerated its monoclonal antibody R&D. As of the end of the reporting period, the company had obtained clinical trial approvals in China for 9 monoclonal antibody products (including 4 innovative biologics) covering 13 indications, with 2 monoclonal antibody products and 1 combination therapy approved in China.Clinical TrialsApplication accepted. The biosimilars trastuzumab, adalimumab, and bevacizumab, as well as the biologic innovative drug recombinant human-mouse chimeric anti-CD20 monoclonal antibody injection, have all entered Phase III clinical trials and are expected to sequentially submit marketing applications. Rituximab has been submitted for production approval and included in the priority review program, with anticipated market approval by the end of 2018.

The Company’s anti-PD-1 monoclonal antibody (HLX10), a biologic innovative drug, in combination with the bevacizumab biosimilar (HLX04) for the treatment of advanced solid tumors has been approved by the National Medical Products AdministrationClinical TrialRegistration Review Acceptance. This is the first domestically produced monoclonal antibody combination therapy regimen to have its IND application accepted in China. This regimen not only represents a further implementation of the company’s combination therapy strategy but also marks a significant milestone in the field of combination therapy in China.

In summary, clinical development of biosimilars targeting TNFα, VEGF, and EGFR, as well as novel biologics targeting VEGFR2 and EGFR, is progressing steadily. Furthermore, Phase III clinical trials for recombinant insulin lispro, recombinant human insulin, and recombinant insulin glargine are proceeding smoothly. In the realm of small-molecule innovative drugs, FC-110 (furinitinib diacid capsules) and PA-824 have entered Phase I clinical trials, while FN-1501 and FCN-437 have received approval for clinical investigation.

Three products have passed the consistency evaluation, with ten more in the pipeline.

In terms of the consistency evaluation, the company closely follows current policies and steadily advances its consistency evaluation work. During the reporting period, the company’s Amlodipine Besylate Tablets (brand name: Shilida), Escitalopram Oxalate Tablets (brand name: Qicheng), and Alfacalcidol Tablets (brand name: Liqing) successfully passed the consistency evaluation.

According to data from Menet, there are currently as many as 61 manufacturers holding production approval for Amlodipine Besylate Tablets. A subsidiary of Fosun Pharma was the first company to pass the consistency evaluation for this product, forming a “tripartite balance” with Yangtze River Pharmaceutical Group’s Shanghai Haini Pharmaceutical and China Resources Saike Pharmaceutical, which subsequently passed the consistency evaluation. In terms of the competitive landscape of amlodipine in the terminal market of Chinese public medical institutions in 2017, the original research manufacturerPfizerWhile accounting for over half of the market share, Jiangsu Huanghe Pharmaceutical holds a relatively small share but is poised to further capture market share through subsequent policy dividends.

According to data from the Menet MED China Drug Evaluation Database 2.0, as of September 12, 2018, Fosun Pharma and its subsidiaries had a total of 17 accepted application numbers for consistency evaluation (excluding those already approved for consistency evaluation, as below), involving 10 drug varieties (excluding varieties already approved for consistency evaluation, as below). The number of consistency evaluation applications was second only to Qilu Pharmaceutical. Among these, 9 accepted application numbers for consistency evaluation were undertaken by the CDE during the reporting period, involving 6 drug varieties. (BioValleyBioon.com）

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