And don't wait, it won't…
"CAR-T is like a spaceship against the background of a civil aviation aircraft"
On the eve of the conference of the Russian Society of Oncohematologists (ROOG) scheduled for June 25, dedicated to cellular immunotherapy in the treatment of oncohematological diseases in adult patients, it makes sense to recall the results of previous discussions about the availability of CAR-T* therapy. In particular, the possibilities of using the so-called industrial** CAR-T therapy have been discussed for several years.
At the traditional forum held in Moscow at the end of 2021, organized by the All–Russian Union of Patients (VSP), among many topics related to the availability of innovative medical technologies and drugs, special attention was paid to cell therapy - the possibilities of using technology, legal and organizational aspects of drug registration, payment models for such treatment. The speakers talked a lot about how to expand access to cellular drugs and personalized medical products.
Then in one of the reports it was indicated that by the end of 2020, the share of innovative drugs in circulation in Russia in value terms decreased to 14.6% (in 2019 – 15.8%). According to the IQVIA study (which included 24 EU states and 10 countries outside the Union), our country was on the 31st line in terms of the level of provision of innovative therapy in 2016-2019, defined as the number of registered and included in the reimbursement lists of innovative drugs (for the Russian Federation, this is a list of VED, purchases under a regional benefit), neighboring in This ranking is with Turkey, Latvia and Lithuania. During the analyzed period, only 26 out of 152 innovative drugs included in the study were registered in the Russian Federation – five times less than in Germany and Denmark, which topped the rating. At the same time, most of them – 21 drugs – were introduced to the Russian market in 2016-2017.
For a number of diseases, it is innovative personalized medical products that can become the main way to prolong a patient's life and ensure a longer remission. Currently, CAR-s have been developed and registered in the world for such types of tumors as multiple myeloma, B-cell acute lymphoblastic leukemia, diffuse large-B-cell lymphoma, etc.
Every year, several CAR-T drugs are registered in the world. In particular, on May 25, 2022, the European Medical Agency registered the second CAR-T drug for the treatment of adult patients with multiple myeloma treated with three main groups of drugs (immunomodulators, proteasome inhibitors and anti-CD38), in which progression is observed against the background of the latter scheme.
However, this type of therapy is not yet available for Russian patients. Work is underway to adapt Russian legislation to the appearance of this type of individual drugs. The need to establish the specifics of the circulation of certain types of high-tech drugs***, taking into account the specifics of their production, was prescribed back in September 2021 in the VSP roadmap, compiled following the results of the II Forum of Patient-oriented Innovations.
We are talking about complex and high-tech products, which, according to one of the speakers of the session, are "a spaceship against the background of a civil aviation aircraft."
Last fall, Russian legislation was not yet sufficiently adapted to the widespread introduction of cellular drugs into clinical practice, but significant progress has taken place in this area in a relatively short time – in early February 2022, the Ministry of Health of the Russian Federation submitted amendments to Federal Law No. 61 "On the Circulation of Medicines".
In particular, for high-tech medicines, to which CAR-T belongs, mandatory testing of samples of the first three imported series, annual mandatory testing and mandatory labeling are canceled, which makes it possible to import and enter into civil circulation of such drugs.
Indeed, this breakthrough therapy requires serious financial costs. However, we are talking about the treatment of the most serious diseases, which in themselves create a significant burden on the healthcare system (long-term treatment, hospitalization, development of complications requiring treatment, additional burden on doctors, etc.), and on the economic indicators of the country (disability of the patient, disability with associated costs, etc.).
It is necessary to reconsider approaches to financing such therapy and consider such costs in the healthcare sector as investments, where the benefits will be additional years of the patient's life, the absence of the need for long-term continuous treatment, improving the quality of life, reducing the burden on the healthcare system, sustainable economic growth in the long term.
Currently, such drugs, which are part of complex, high-tech treatment methods, are financially supported by programs of VMP (high-tech medical care) or clinical approbation (CA), but they need their own financial mechanisms, since they differ markedly from traditionally used drug regimens in a number of parameters. In addition, the practice of immersing a drug in the reimbursement system provides for a "gap" of 1.5–2.5 years from the date of registration of the drug to its inclusion in clinical recommendations, VED, payment models of VMP and CA. That is, patients with severe progressive diseases, in particular with oncohematological, are forced to wait for the most effective treatment options for a long time. Such an expectation can lead not only to deterioration of their condition, but also to premature deaths. Do not forget that many refusals are issued annually for the approval of the SC protocols.
VSP advocates the development of a strategy for immersing innovative therapy in the healthcare system, noting that the federal project "Medical Science for Humans" of the state program "Development of Healthcare" provides for "active development, development and introduction of modern medicines based on innovative technologies, such as gene therapy and cellular drugs." At the same time, the VSP emphasizes, there are no well-developed approaches to the immersion of "expensive, but highly effective gene and cell therapy into the healthcare system". Providing gene therapy, for example, at the expense of the Circle of Good Foundation, "may be a temporary tool for providing certain categories of patients, but does not replace a systematic approach to solving the issue."
All participants in the healthcare system understand that a balance is needed between ensuring innovation and optimizing the budget. Therefore, it is very important to provide a certain legal mechanism to accelerate the entry of innovative medicines into the market, and at the same time to revise the reimbursement models for gene therapy, CAR-T and other advanced treatment methods.
New mechanisms and tools are needed. For example, CAR-T is a high–tech and cost-intensive method, therefore, in paying for such therapy, it is advisable to use innovative approaches with risk sharing between the state and the manufacturer, who is ready to be responsible for the effectiveness of using the product in each specific case. In such a model, reimbursement of the cost may be provided, depending on the level of achievement of the declared effectiveness of the drug.
In order to implement this approach in practice, which is already used in a number of countries, it will be necessary to adapt the existing regulatory legal acts to the task. In particular, to introduce the possibility of full or partial payment to the manufacturer of the drug based on the effect obtained in real clinical practice, including taking into account its duration.
VSP experts also propose to develop a monitoring system for patients who have received gene or cell therapy. "Given that gene and cell therapies can have a delayed, difficult–to-predict effect over a long-term period (>10 years), the creation of a unified patient registry will allow for systematic monitoring of changes in the condition of patients who have received such therapy, both for the purpose of providing medical care to the patient himself, and in order to improve therapy methods in general," it says in the VSP roadmap.
This week, on June 25, a new round of discussion of the prospects of innovative CAR-T methods will take place at the site of the Russian Society of Oncohematologists, where leading experts will discuss the place of cellular immunotherapy in the treatment of oncohematological diseases in adult patients.
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*CAR-T – T-lymphocytes (immune cells) of the patient, to which the chimeric antigen receptor (CAR) is attached. It is this specific receptor that allows the T cell to target and destroy a certain type of tumor cells. Technically, this is done as follows: blood is taken from the patient, T lymphocytes are isolated from the blood, frozen and sent to production, where a certain chimeric antigenic receptor (CAR) is added to the T cells. The finished CAR-T drug is frozen and sent to the clinic, where it is administered intravenously to the patient. The course of treatment consists of one injection.
**"Industrial" CAR-T is commonly referred to as an individual cellular drug produced at a centralized production site. Such a drug undergoes all the necessary drug studies and is registered as a medicinal product. In Russian legislation, such drugs are classified as high-tech medicines.
***A high-tech drug that may fall under the definition of a somatic cell-based drug or the definition of a tissue engineering drug and a gene therapy drug should be considered as a gene therapy drug. Thus, CAR-T is considered as a gene therapy drug. In European regulatory practice, such drugs belong to the medicines of advanced therapy (Advanced Therapy Medicinal Products).
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