GSK Shifts Focus from Cell and Gene Therapy to Small Nucleic Acid Drugs with Strong Pipeline and Market Potential

GSK recently announced its decision to end investment in cell and gene therapy, showing greater optimism for the development of small nucleic acid drugs. Why has GSK abandoned the currently popular cell and gene therapy, and what prospects does it foresee for small nucleic acid drugs?

 

 

In the field of cell and gene therapy, the current focus is on CAR-T therapy (Chimeric Antigen Receptor T-Cell Immunotherapy) within cellular immunotherapy. This is a novel precision-targeted cancer treatment that is precise, rapid, highly efficient, and has the potential to cure cancer.

 

In recent years,CAR-TTherapy for treating tumors is gradually becoming a new field in tumor immunotherapy. In 2013, the first "CAR-T" cell was synthesized by the U.S. National Cancer Institute. In the past few years, more than 20 companies, including international pharmaceutical giants such as Celgene and Novartis, as well as China-based Nanjing Legend, Fosun Kite, Wuxi Juno, CARsgen Therapeutics, Shenzhen PreGen, Bluebird Bio, Innovent Biologics, and Hekang Biotechnology, have been developing CAR-T therapies.

 

As of now, eight CAR-T therapies have been approved globally. The CAR-T therapies currently marketed in China include Yikaida (Axicabtagene Ciloleucel Injection) by Fosun Kite and Benoda (Relmacabtagene Autoleucel Injection) by Shanghai JW Therapeutics. The marketing application for Hejilun Sai by Hekinno Biopharma was accepted by the National Medical Products Administration in December last year and is proposed for inclusion in the priority review and approval process.

 

According to the data from the PatSnap Global New Drug Intelligence Database, as of December 15, 2022, the number of CAR-T clinical trials conducted globally reached 2,035, with 1,096 conducted in China, accounting for 53.86%.

  

In the field of cell therapy, GSK had made extensive arrangements. However, following the departure of former CSO (Chief Scientific Officer) Dr. Hal Barron in August 2022 and the succession of Tony Wood, Senior Vice President of Pharmaceutical Sciences and Technology, GSK made significant adjustments to its R&D pipeline in the cell therapy sector. According to media reports, in October 2022, GSK terminated its TCR-T (T-cell receptor-engineered T-cell therapy) collaboration project with Lyell Immunopharm for solid tumors and exited the Cell Therapy 2.0 Alliance. In the same month, GSK also abandoned the NY-ESO cell therapy collaboration with Adaptimmune. In December 2022, GSK's collaboration plan on TCR-T therapy with Immatics was also announced to be terminated.

 

According to reports from multiple media outlets, Emma Walmsley, Global CEO of GSK, recently mentioned that although cell therapies such as CAR-T have achieved significant success in treating hematologic tumors, this field has become overly crowded. Expanding these therapies to solid tumors is proving to be more challenging than initially anticipated. Considering all the development and manufacturing costs, as well as potential risks, continued investment in the gene and cell therapy sector may not be the best choice for GSK.

 

 

The industry also believes that GSK's future focus will be on oligonucleotide drugs.(i.e., small nucleic acid drugs)Small nucleic acids refer to oligonucleotide molecules including small interfering RNA (siRNA), antisense oligonucleotides (ASO), microRNA (miRNA), RNA activation (saRNA), and nucleic acid aptamers (Aptamer). Small nucleic acid drugs, composed of nucleotides, represent an entirely new category of drugs distinct from small molecule drugs and antibody drugs. Among them, antisense oligonucleotides (ASO) and small interfering RNA (siRNA) are widely used. Both primarily target mRNA (messenger ribonucleic acid) in the cytoplasm, regulating protein expression by base-pair complementarity recognition and inhibition of target mRNA, thereby achieving therapeutic effects for diseases.

 

Data from a 2022 research report by Gortec Investment Research Institute showed that from 2013 to 2018, six small nucleic acid drugs for the treatment of rare diseases were launched globally. Since then, small nucleic acid drugs have entered a rapid development phase, with seven drugs launched in the past four years. The clinical trial cycles for these drugs are mostly 5-6 years, shorter than the traditional drug R&D cycle. Due to advantages such as abundant candidate targets, shorter R&D cycles, and high clinical development success rates, small nucleic acid drugs are increasingly gaining attention from pharmaceutical companies. In terms of therapeutic areas, 86% of the marketed drugs are used for treating rare genetic disorders.

 

In 2021, the global sales of the aforementioned drugs exceeded $3 billion. A recent oligonucleotide synthesis market report released by Research And Markets mentioned that the global oligonucleotide synthesis market size reached $6.1 billion in 2022 and is expected to grow to $19.9 billion by 2030, with a compound annual growth rate (CAGR) of 15.9%. The U.S. oligonucleotide synthesis market size was approximately $1.7 billion in 2022. As the world's second-largest economy, China’s oligonucleotide synthesis market size is projected to reach $4.9 billion by 2030, with a CAGR of 21.5%.

 

 

A representative product in the small nucleic acid drug category is Nusinersen Sodium, a treatment for Spinal Muscular Atrophy (SMA), which once garnered significant attention in China due to its "7 million yuan" high price tag and was later included in China's national medical insurance catalog at a price of 33,000 yuan during the 2021 national medical insurance negotiations. According to Biogen's 2022 annual report, although Nusinersen Sodium's sales declined by 5.83% year-over-year in 2022, it still reached 1.794 billion U.S. dollars.

 

In addition to GSK, pharmaceutical giants such as Novartis, Roche, AstraZeneca, Novo Nordisk, and Takeda have also entered the small nucleic acid drug field through cooperation, mergers, and acquisitions.

 

In China, Sirnaomics is a representative company in the research and development of small nucleic acid drugs. Established in the United States in 2007, it is the world's only clinical-stage RNA therapeutics company operating in both China and the U.S., with a rich pipeline of innovative nucleic acid interference drug candidates. The company has not yet had any products approved for marketing. Among its R&D pipeline, the small interfering drug STP705 is at the most advanced stage of development, with clinical trials for squamous cell carcinoma in situ having entered phase II. In addition, the drug is also being developed for indications such as non-melanoma skin cancer and liver cancer. Sirnaomics has also established multiple collaborations with domestically listed companies such as Innovent Biologics, Junshi Biosciences, Walvax Biotechnology, and Xiangxue Pharmaceutical.

 

Another representative local company focusing on the research and development of small nucleic acid drugs is Ribo Biotech. Its pipeline mainly includes small interfering RNA (siRNA), antisense oligonucleotides (ASO), and aptamer drugs. According to information disclosed on the company’s official website, RBD4988, an antisense nucleic acid drug for type 2 diabetes, has completed one Phase I clinical study and three Phase II studies globally. In China, two Phase II clinical trials for type 2 diabetes have also been successfully completed. RBD1016, a small interfering RNA (siRNA) drug under development for hepatitis B, has completed clinical trials in Australia.ⅠaPhase Research, in Hong Kong, ChinaⅠPhase b clinical research is currently underway.ⅡPhase clinical trials are in preparation. Another small interfering RNA (siRNA) targeting Caspases 2 for optic nerve protection has completed one clinical trial globally.ⅠPhase research and one Phase II/III international multicenter clinical trial.

 

On January 31 this year, the National Medical Products Administration (NMPA) also accepted the clinical trial application for JS401 Injection, a lipid-lowering drug jointly developed by Junshi Biosciences and Runjia Pharmaceuticals. The drug is a small interfering RNA (siRNA) targeting angiopoietin-like protein 3 messenger RNA, and it is also the first small nucleic acid drug targeting angiopoietin-like protein 3 to be accepted by the NMPA.

 

Reporter Wang Kala of the New Jingbao

Proofread by Yang Xuli