Increase the chances: a domestic drug is designed to help in the fight against cancer

Last week, information appeared in the media about a letter addressed to the Minister of Health Mikhail Murashko, in which concern was expressed that the Russian pharmaceutical company BIOCAD was planning to launch an accelerated clinical trial of a biosimilar of a drug intended for the treatment of certain types of breast and stomach cancers. The author of the appeal, the international pharmaceutical company AstraZeneca, claims that this may pose a risk to test patients with HER2—positive metastatic breast cancer. A public discussion immediately developed around this issue. Izvestia investigated whether the fears were justified.

Reasons for concern

The fact that AstraZeneca sent an appeal addressed to Mikhail Murashko became known on April 24. In it, the company asks for the suspension of the research permit due to "potential risks to the life and health of participants," and also states that the drug BCD-267 is "insufficiently studied" and that there is "no regulatory framework" for biosimilars of ADC (a class of antibody conjugate drugs with a cytostatic agent (cytostatic)).

"The use of the investigational drug BCD—267 in the framework of the study, in the absence of evidence of comparability of the structure and biological characteristics with the reference drug, may lead to an unfavorable benefit-risk ratio for participants in the clinical trial," the appeal quotes "Газета.ги ".

However, during the discussion, information appeared that AstraZeneca produces the drug "Enherta" (trastuzumab deruxtecan), whose biosimilar is BCD-267. The drug is considered extremely effective in the fight against certain types of breast and stomach cancers. Nevertheless, its cost remains quite high and the drug is simply unavailable for most Russian patients. In this situation, the development of the BCD-267 biosimilar is not a matter of competition, but an opportunity to save the lives of thousands of patients who cannot receive treatment today.

According to statistics, the number of patients who have been living for more than five years since their cancer diagnosis has increased by almost 9%. According to the Minister of Health Mikhail Murashko, this progress became possible due to the development of domestic scientific developments and modernization of the healthcare system.

Risk assessment

One of the arguments is that ADC drugs have specific features, and there is no experience in registering their biosimilars in world practice, which means that there is no necessary regulatory framework. However, there are no clear arguments in the letter that the Russian drug does not meet safety requirements.

ADC (Antibody-Drug Conjugates) are innovative anticancer drugs that are complex molecules consisting of a monoclonal antibody and a cytostatic agent connected by a special linker. It is believed that these drugs work on the principle of "smart delivery": the antibody acts as a "gunner" that recognizes specific markers of tumor cells, and the cytostatic agent performs the function of a powerful damaging element that activates directly in the tumor tissue.

The creation of biosimilars of such drugs is indeed an extremely difficult task requiring the highest level of technological development. Unlike relatively simple biosimilars, where it is sufficient to prove structural similarity with the original, for ADC it is necessary to reproduce not only the antibody itself, but also the complex system of its conjugation with the cytostatic agent, as well as to confirm the identity of the mechanism of action. The slightest deviations in the structure of the molecule can significantly affect both the effectiveness of the drug and its safety. The same thing is written by and "Газета.ги ".

At the same time, the experts interviewed by Izvestia emphasize that the question of the sufficiency of research on the new BIOCAD biosimilar drug BCD-267 requires balanced consideration. According to official data, the developer has provided a complete set of preclinical data that meets both Russian and international regulatory requirements. At the same time, the permission of the Russian Ministry of Health to conduct a clinical trial was obtained after the standard procedure of expert evaluation of the submitted materials. That is, there is no question of any "accelerated procedure".

— The criticism sounds like the Ministry of Health and its expert institution are not able to evaluate such a complex drug. But the original drug was also evaluated by the Ministry of Health," Alexey Kedrin, Chairman of the Board of the Association of Pharmaceutical Manufacturers of the Eurasian Economic Union (AFPEAEC), said in an interview with Izvestia.

An innovative approach

It is worth noting that the technology of creating ADC drugs is not new - the first drugs of this class appeared in medical practice about 25 years ago. Today, more than 20 similar drugs from different manufacturers have been registered in the world, which indicates that the technique has been developed. However, each new ADC drug, especially a biosimilar, requires careful testing due to the complexity of its molecular structure. In Russia, in addition to BIOCAD, at least two companies are also developing ADC, which confirms the prospects of this area.

Industry experts point out that such discussions between developers of original drugs and creators of biosimilars are common practice in the pharmaceutical market. On the one hand, companies developing original drugs naturally seek to protect their investments. On the other hand, the emergence of biosimilars really helps to reduce prices and significantly increase the availability of treatment. In this case, the key factor is the decision of the regulator, which must objectively assess the ratio of benefits and potential risks of a new drug.