BioLink and BioValley Jointly Launch the ''Cell Therapy R&D Illustrated Handbook''

CAR-T cell therapy has now become a new choice for tumor patients. Based on the high efficacy of CAR-T cell therapy shown in clinical studies, many front-line medical workers, patients and their families, and investigators in this field are very optimistic about it.

But globally speaking, as the number of CAR-T approvals grows, the CAR-T prescriptions that should be rising accordingly merely show a slow increment. What is holding back the use of CAR-T in the real world?

Current situation of international CAR-T utilization 

The FDA has by far approved six CAR-T therapies for marketing, covering five hematologic tumors: diffuse large B-cell lymphoma (DLBCL), acute lymphoblastic leukemia (ALL), follicular lymphoma (FL), mantle cell lymphoma and multiple myeloma. According to a study issued by the U.S. National Cancer Institute (NCI), there was no increase in monthly CAR-T prescriptions in 2021, and prescriptions in the second half of 2021 were similar to those in the same period of 2020. More notably, two new CAR-T cell therapy products were approved by the FDA in 2021. In addition to Breyanzi, for which products of the same type are already available for the indication, Abecma, another BCMA CAR-T product, was approved for a completely new indication, multiple myeloma. With the new product and indication, the CAR-T sales in the second half of 2021 in the U.S. did not rise as we expected, but levelled or showed little difference with those in the second half of 2020, a period when the COVID-19 pandemic still swept over the world.

Barriers to CAR-T utilization

Real-world data that do not match expectations suggest that something went wrong when it comes to using CAR-T in real life. 

Patient health status and disease progression 

Current CAR-T cells need to be prepared using the patient’s own cells, but most tumor patients who meet the criteria for CAR-T use have basically received multiple lines of therapy, which severely damaged their immune systems. It is a more critical issue whether qualified and sufficient T cells can be provided to be transformed into CAR-T cells. Secondly, such patients usually suffer from recurrent tumors with their disease deteriorating to advanced stages. The exacerbation is so fast that they may not stay the course when the cell preparation is completed that generally requires 2-4 weeks.

Production

Factories and manufacturing challenges

Autologous CAR-T cells are prepared in a single person and single batch, which means a complete production facility needs to be prepared for a patient individually. It is a relatively big challenge for factory production equipment and space, as it requires manufacturers to build factories in advance that will cost heftily. Bristol-Myers Squibb once said that the capacity of CAR-T drug Abecma cannot meet the demand of patients in the market. In recent years, several major CAR-T developers have been moving into top gear to lay out new cell therapy factories. Apart from the capacity and manufacturing challenges, CAR-T cells actually have a failure rate in preparation. Despite qualified T cells taken from patients, there can be manufacturing issues from the original cells to the finished CAR-T cells, or preparation failures as well as substandard products.

Medical locations and cold-chain logistics

There are only a limited number of hospitals in the U.S. that can currently support CAR-T therapy, so that CAR-T cell infusion is not available in each and every hospital, keeping a majority of patients away from CAR-T cell therapy due to geographical, transportation and expense predicaments.

Furthermore, the transportation of CAR-T cells requires cold chain logistics, and the change of temperature on the way may undermine the quality of the whole product. This problem, however, can be largely solved with the deployment of mRNA COVID-19 vaccine in the U.S.

For the Chinese market, there remains a challenge in terms of medical locations and cold chain logistics.

Price and cost

CAR-T is priced at $300,000-$500,000 in the U.S. In spite of the country's support for innovative drugs and commercial health insurance that exempts patients' full payment by themselves, the out-of-pocket portion remains a significant expense for many patients, especially after multiple treatments.

In addition to the cost of CAR-T treatment itself, the pretreatment before the patient receives the CAR-T infusion, the management of side effects after the infusion and the charge for hospital care need to be calculated separately.

In China, where CAR-T treatment is not yet covered by medical insurance, the payment issue for CAR-T cell therapy is still difficult for patients and their families. Nevertheless, several commercial insurance policies have now covered CAR-T cell therapy, which may contribute to the accessibility of CAR-T.

Summary

Compared with the bullishness of CAR-T cell therapy within the industry, its commercialization performance has not yet quite cut the mustard. How to improve the accessibility of CAR-T cell therapy to promote its sales is a matter to be reckoned with at present.

BioLink joined hands with BioValley to launch the “Cell Therapy R&D Illustrated Handbook” based on multiple researches, combining actual cases to sort out the critical links and details of cell therapy process from project approval, drug evaluation, process development/transfer, quality analysis, registration for commercialization and process scale-up, thereby empowering you to quickly master the key technologies and the whole process of cell therapy drug R&D.