In the past june, the national drug authority has announced the successful listing of more than 10 new medicines through priority approval。
Among them, the country's first cytotherapy product, the aquiluncai injection fluid, received high levels of industry interest and china finally had a “zero breakthrough” in cytotherapy products。
In an interview (www. Thepaper. Cn), cytology was described by experts as “historical progress” and the country finally had products on the market, but it had not splattered too much water among the patients。
Cytology has been labeled as a “nomadic price” since its early appearance on the market abroad, which has led many commercial companies to put together and patients to lose sight of it. What kind of therapy is cell therapy? How can cytotherapy products be sold for millions? What are the risks of cell therapy? Which patients can benefit from this? The multiple press interviews sought answers to these questions。
Price millions? Restar kate: pricing options not yet finalized
"would you like to give a million dollars to cure cancer?" on 28 june, the head of the lymphoma family's group, zhu hong fei, raised such a question in a friendly circle, but at the same time said that it was not a choice。
On 23 june, the national bureau of medicine released a message that the aquillonse injections declared by restar kate biotechnology ltd. (hereinafter: restar kate) became the first cytology product approved for listing in the country for the treatment of adults with re-emerging or incurable large b cell lymphoma after receiving a second-line or more systematic treatment。
In the week following the announcement, several versions of this recently approved cell therapy product, “price information”, were transmitted to the micro-clinics of lymphoma patients: 900,000, 1 million, 1. 2 million。
In response to a media response to the pricing of the akironse injection fluid that is circulating online, restar kate stated that the pricing formula is not yet finalized and is being communicated across multiple lines。
The aquillonse injection from restar kate is not an indigenous research product. In april 2017, kite pharma, the united states, in cooperation with the re-start medicines, established re-star kate and introduced aquillence fluid into china. On 28 august 2017, the united states company gilid purchased kite pharma at $11. 9 billion, and on 18 october that year the product was listed with the approval of the united states food and drug regulatory authority (fda), followed by concerns about the sale price of $373 million (approximately rmb 2. 4 million)。
Why would a drug sell for millions
Letting a cell treat is a case of a real patient, emily, a leukaemia girl in the united states, who has lived 10 years without tumours after cytotherapy。
Domestic and foreign research data show that the overall reduction rate for the treatment of incurable re-emergence of large b-cell lymphoma (orr) by aquilencÉ is 83 per cent, the total mitigation rate (cr) is 58 per cent, the median total survival period (os) is 25. 8 months, the median follow-up period is 51. 1 months, and the os rate can reach 44 per cent。
Long-term survival, like emily, is the best hope for cancer patients to “cure” cancer。
Dr. Yang qingmin, director of oncology biotherapy at the general hospital of the liberation army, which has been conducting clinical studies on immunocellular cells for many years, explained that the indicator “total decomposition” to evaluate the effects of treatment on tumours, for example, was a petct examination for patients and no tumours were visible on the image. Full decomposition is an important goal for doctors and patients after treatment, and 58 per cent of total decomposition means that more than half of the patients have their tumors removed from their bodies after using the therapy。
Following the approval of akilensai injection fluid, guo hong fei stated to the news that this was a historic medical advance, but that high prices were also expected to be an enormous financial burden for patients。
Guo hong fei indicated that if the drug was sold for a million dollars, the patient would be denied it, too high a price would make the patient feel that they had nothing to do with the new treatment, so there was nothing to discuss with the patient。
The price of new medicines needs to be balanced between encouraging innovation by commercial companies and making it accessible to patients。
According to yang, this is a very difficult issue, and many genetic companies have invested in the development of cytotherapy, and in addition to the development of medical technology and life-saving services, commercial factors exist。
“i feel that there is a need to find a balance between recycling inputs and making profits at prices that are not acceptable to most patients.” yang qingming has proposed an ideal price of around $500,000, which is expected on the basis of a trade-off between the cost of cytotherapy, the commercial benefits of investing in research and development enterprises and the acceptability of patients。
"personally customised" cell therapy has better effects on blood tumors
To figure out why cytology is so expensive, first of all, what is cytology? This treatment is explained in some official regulations。
Management of clinical research and conversion applications for body cell treatment (pilot) issued by the national health commission in 2019
It was suggested in the exposure draft that body cell therapy is the treatment of body cells originating in the human body or in foreign form, which are retrenched (or implanted) after in vitro operation. This in vitro operation includes the in vitro activation, induction, augmentation, generational and screening of cells, as well as the treatment of drugs or other changes in cell biology。
The cytology product is also known as the “private custom” product, as it is extracted from the human body, operated in vitro and returned to the body。
Yang qingming explained to the news that, in contrast to traditional medicines, it was difficult to produce large quantities of cytology products, which required cells to extract the patient's own blood, separate the cells and then develop and treat them。
“when immune cells are separated from blood, their activity is influenced by factors such as the age of the patient, the history of drug use, etc.” according to yang qingming, a series of measures for clinical treatment from cell collection, culture, genetic modification and re-entry are individualized, which is called “private customization”。
The current type of cytology study, depending on the mechanism of action, consists mainly of tumour immersion of lymphocytes (tumour-infiltrating lymphocytes, tils), embedded antigen receptor t-cells (chimeric antigen modified tcells, car-t) and engineering t-cell receptors (t-cellor-engineered tcells, tcr-t)。
Yang qingming said to the news that the first cell therapy product in the country that was approved was the t-cell embedded in the antigen receptor, the car-t-cell therapy. It is based on the genetic modification of the patient's t-cells, the expression of an embedded antigen receptor (car) aimed at targeting antigen cd19, an antigen protein expressed on the surface of multiple blood tumour cells, including cell b lymphoma and leukemia cells。
Yang qingming explained that the current study of the car-t cell therapy for lymphoma at home and abroad focused mainly on cd19, cd20 and covered a small number of other targets, with a high overall homogeneity。
“in general, the current active car-t cell therapy is concentrated mainly on blood tumours, and many of the results of studies in real tumours are unsatisfactory and unsatisfactory.” yang qingming explained the reasons for the large number of physical tumors, such as lung cancer subtypes, the complexity of antigens and the relative concentration and stability of antigens for blood tumours。
In yang's view, the car-t-cell therapy in blood tumours is a treatment that is likely to be comparable and may even gradually replace transplantation. Lymphatic leukaemia, for example, used to be the best transgenerative, but now car-t-cell therapy can also significantly improve the full relief and lifetime of lymphatic leukaemia patients。
“the price of leukemia for stem cell transplants is currently around $500,000.” in an interview with the press, yang qingming stated that the treatment would be promising in the future if the price of akilense injection fluid was contained at around $500,000。
At present, akilensai injector fluids have been approved with adaptation certificates for adults who have experienced a relapse or difficult treatment of a large b cell lymphoma after undergoing systematic treatment on the second line or above。
According to guo hong fei, from the beginning of this year to the present, there are now 2,000 large b-cell lymphoma patients who have joined the lymphoma group, 300 of whom have been treated with car-t-cells, which are compatible with the adaptation fluids recently approved for aquillence。
“as time passes, at least 1,000 of these 2,000 patients will need car-t-cell treatment, and some of them will be transformed from lymphoma to a re-emergence of lymphoma of large b cells. "hung fei gu said:。
Despite expectations that new medicines will be approved for listing, high prices make it difficult for many patients to afford. According to guo hong fei, this is a problem for all new medicines to be listed, and the latter will become more affordable as technology improves, competitive products, etc。
Cell-factor storms are common adverse effects
How safe is cell therapy as an emerging therapy? Yang qingming described the safety of akilensai as generally good, as confirmed by early clinical trials. The most common and important adverse reaction of cart-t cell therapy in clinical treatment is the release of cytogenesis and neurotoxicity。
The cell-factor release syndrome, the cell-factor storm, is not new to people who have recently experienced a new coronary outbreak. Many patients with severe pneumonia had had cyto-factory storms during the wuhan new crown outbreak。
In a previous press interview, chen jia xie, director of the sanitary department of the riggin hospital, affiliated with the shanghai medical college, explained that the lung damage of many seriously ill new coronary pneumonia patients was not caused by direct bacterial or viral injuries, but was mainly caused by the “excusable” immune response of the new coronary virus。
Cell-factor storms refer to large numbers of immunocellular cells entering the patient's body and the organs of his or her stoics, where excessive “cell-factor” excessive attacks on tumours cause organ damage and functional impairment。
In case of cytogenstorms, the patient may experience heat, local oedema, and signs of body or local inflammation, such as lower blood pressure, may lead to organ failure if severe。
Last year, the team from the biotherapy section of the general hospital of the liberation army published a paper in the medical journal blood, " the study of t-cell treatment of incurable/recurring b-cell lymphoma after pre-treatment " , a two-target cd19/cd20 series of embedding antigen receptors. The results of the study of objective mitigation rates show an objective mitigation rate of 79 per cent, with a total mitigation rate of 71 per cent, a non-progressive survival rate of 79 per cent for six months and a non-progressive survival rate of 64 per cent for 12 months. In the case of adverse effects, the incidence of cytological emission syndrome in patients is about 50 per cent, of which 36 per cent are grade 1-2 and 14 per cent are level 3. No toxic effects associated with the nervous system of level 3 or higher were observed。
“persons in the course of treatment who show signs of cytological emission syndrome should be promptly detected and treated to control symptoms as soon as possible. Avoiding adverse physical effects. This places higher demands on the clinician.” yang qingming indicated。
It is worth mentioning that, in order to ensure that cell therapy is stable in the country and that more patients benefit from it while mitigating the risks associated with treatment, china's first guidelines for the clinical management of the nhl by-effects of the treatment of nhl by car-t-cells have been published, with the participation of experts from more than 30 national medical institutions, organized by the china research hospitals institute of biotherapy. The book is currently in the process of being published with a view to providing a more practical guidance programme for clinicians in dealing with adverse reactions associated with the treatment of car-t cells。
