First CAR-t treatment…Long-term survival in half of relapsed/refractory DLBCL and ALL patients
Medication cost is expected to be at least 500 million…Controversy over reorganization of payment and pharmaceutical benefits is inevitable
“The era of ultra-high-priced drugs begins, researchers need to hurry to lower the hurdles and localize them”
Pandora’s box opened.
On the 5th, Novartis Korea (CEO Josh Benugopal)’s CAR-t treatment Kimria (Tisagen Rexcel) obtained domestic approval.
Although it cannot be said that it has been four years since FDA approval in 2017, there is a lot of controversy because it is a permit that was made in a situation where policy preparations are insufficient, from the definition of a drug to the cost of a drug that is expected to exceed 500 million.
It is a miracle treatment that has raised the survival rate of patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) and B-cell acute lymphocytic leukemia (pALL) with little chance of regeneration to close to 50%. It is raising concerns that it may become the synonym for’Hope Advisor’ as the first runner in the tenth.
Starting with Kimlia, billions of treatments are expected to appear in succession in the near future, so there are concerns that Kimlia’s approval could be the prelude to the era of medical inequality.
On the 23rd, Novartis Korea held a press conference in commemoration of Kimlia’s approval. A heavy atmosphere followed by a realistic task.
◇The first personalized cell/gene therapy…opens up long-term survival opportunities for end-stage blood cancer patients
Kimria is one of the methods of genetically recombining the T cells collected from the patient so that a chimeric antigen receptor (CAR) that recognizes a specific antigen of cancer cells can be expressed on the surface and then injected into the patient’s body again. It is a customized anticancer drug.
With a single treatment, patients with untreated end-stage blood cancer reach complete remission, maintain a continuous response, and open the possibility of long-term survival, drawing attention as a’miracle cure’.
The indications that were approved in Korea on the 5th are recurrent and refractory diffuse large B cell lymphoma (DLBCL, Diffuse Large B Cell Lymphoma) and B cell acute lymphocytic leukemia (hereinafter referred to as pALL, pediatric Acute Lymphoblastic Leukemia) under 25 years of age. have.
Most of these patients can get a good effect from the first treatment, but if the results of the first treatment are not good, the response rate from the second treatment drops significantly, and if even that does not respond or recurs, the life expectancy is only about 6 months. The prognosis is poor.
Nevertheless, in a clinical study of these patients, Kimlia suggested long-term survival for about half of the participants.
In the JULIET study in patients with diffuse large B-cell lymphoma, more than half of the patients had a response, including 39.1% of patients reaching Complete Response (CR), and an ELIANA study in patients with acute lymphocytic leukemia. In, 82% of patients reached complete remission within 3 months.
The high response rate leads to prolonged survival, and about half of the patients whose life expectancy was only 6 months gained the possibility of long-term survival.
In this regard, Professor Wonseok Kim of the Department of Hematology and Medicine of Samsung Medical Center said, “In addition to the clinical research conducted by selecting patients in good condition, as well as the Real World Data confirmed in the actual treatment environment, 50% of patients survived for more than 2 years. It was close,” and added meaning as “a epoch-making effect that increased the survival rate from 0% to 50%.”
◇Advanced Renewable Bio Act No. 1 treatment…
Kimria collects and freezes a patient’s blood sample (T cells) from a hospital and sends it to an overseas manufacturing site, where it undergoes genetic manipulation and cell culture to produce personalized cells, and then imports them back to Korea to manufacture CAR-t It is administered to the patient after chemical treatment so that the cells are well received by the patient.
Unlike conventional drugs that were mass-produced in factories, it is manufactured as a customized treatment that can only be applied to the patient through one cycle per patient, and in each process, not only collaboration between medical staff and pharmaceutical companies is required, but also tests required by regulatory authorities The items are also strict.
As such, the concept itself was very different from the existing medicines, so there was not much controversy before the approval. In particular, the limitations of domestic law, which makes it difficult to send blood overseas, has been hampered.
Nevertheless, it was difficult to obtain permission through the Advanced Regenerative Bio Act, which took effect in August last year, and it is expected that the drug will be available in Korea as early as May.
Currently, Samsung Medical Center and Seoul National University Hospital, Severance Hospital, St. Mary’s Hospital, Asan Hospital, etc. are forming a team to introduce Kimria and spur education and training.
It is known that some patients are already waiting to take Kimlia, but it remains to be seen whether the drug will be available in May. As such, there are a number of unresolved challenges.
Most of all, the cost of medication, which is expected to exceed 500 million won, is the biggest obstacle, but the scope of Kimria’s drug cost and the scope of treatment and treatment that are not included in the drug cost are ambiguous due to a process different from existing drugs It’s not an easy challenge.
The intervention of medical staff is required in various processes from blood collection to administration, but the number has not been established yet.
In addition, as it takes 4 to 5 weeks to produce a treatment after blood collection, there is also a problem that the patient may fall into a state that cannot be administered in the meantime.
Not only is an effort to reduce the production period, but it is also necessary to worry about the loss that may occur in the meantime.
First of all, each hospital and the Novartis legal team are looking for a solution head-to-head, and they are expected to draw meaningful results sooner or later.
In addition, the management explained that Kimlia has submitted relevant documents so that she can be quickly recognized for benefits, and is also considering a support program that can increase the accessibility of patients before paying.
Furthermore, regarding the production period, the management affirmed that the management will bear the risk so as not to bear the cost to the patient if the drug is not finally administered to the patient.
◇Professor Won-Seok Kim of Samsung Medical Center “I need to reconsider the 5% self-pay rate for anticancer drugs”
Among the various challenges, the most practical limitation is also’health insurance benefits’.
As the survival rate of 0% can be raised to 50% with only one medication, it is desperate for the patient, but it is questionable whether the benefit can be applied quickly in terms of health insurance finance.
Even if the current indication is limited to patients, about 600 to 1,000 patients per year are expected to be the target of Kimlia’s medication. If calculated at 500 million per patient, it is 300 to 500 billion.
In the future, it is difficult to estimate the size of the market as the indications are likely to expand from relapsed/refractory patients to initial treatment patients.
If health insurance is not applied, individuals have to pay for the drug, but there are not many terminal cancer patients who can afford to pay. This is the biggest challenge that has come into reality with Kimlia’s permission.
In fact, Kimlia’s global sales, announced by Novartis last year, amounted to about 500 billion won, and even with the addition of competing products, the global market for CAR-t treatments has just surpassed 1 trillion won.
This means that even in other countries, the number of patients who can actually access CAR-t treatment is limited compared to the target patients.
The bigger problem is after Kimlia. The emergence of treatments that require billions of treatment costs beyond 500 million are foreshadowing the emergence of treatment costs, and as 3rd and 4th generation CAR-t are waiting beyond the 2nd and 3rd Kimria, the current pay policy is’ It is pointed out that there is a limit to overcoming the’era of ultra-high-priced medicines’.
In this regard, Professor Won-seok Kim of Samsung Medical Center suggested that it is necessary to revise the uniform anticancer drug reimbursement policy, which is currently set at 5% of the out-of-pocket cost.
First of all, he insisted that “(Kimria’s) treatment results are desperate for more than half of the patients who were not promising to get a new life.”
However, “it seems to be holding back the current 5% of the out-of-pocket cost of anticancer drugs,” he said. “If it is 500 million won, the patient pays 25 million won and the rest is tax, so consensus is needed from those who pay health insurance premiums. Do” he pointed out.
Furthermore, he said, “There will be countless numbers of these billions of drugs in the future, and we will need a way to move flexibly rather than being bound by the 5% rule. It is a personal opinion.”
◇Professor Hyung-jin Kang of Seoul National University Hospital “I need to induce localization by lowering research hurdles”
Furthermore, there were voices saying that research on potential new treatments should be promoted to reduce the burden of national finances for foreign drugs and to expand opportunities for patients to participate in clinical research.
It is pointed out that as regulations were made in terms of industry and safety was emphasized, unnecessary tests were increased, which led to a structure in which the price of the treatment was inevitably increased, and even research was not possible unless it was a large company.
In the future, continuous research is needed to further increase the effectiveness of the treatment and lower the cost, but it is difficult to access it for hospitals, universities, and researchers who do not have capital power due to regulations that require strict tests.
In the research stage, not the commercialization stage, it is argued that the regulation should be lowered so that hospitals, universities, and researchers can actively engage in research to make better treatments, and in the process, patients should be able to participate in research.
Furthermore, it is a further addition that the waste of national finances can be prevented if it succeeds in localizing high-priced medicines, one of which is foreign-made.
Professor Kang Hyung-jin of the Department of Pediatrics and Adolescents at Seoul National University Hospital said, “Although adult patients can choose (whether to pay 500 million or give up life), it is not easy for parents to pay a large cost for pediatric cancer patients.” “Saving 50% of the cost is a part of concern” he pointed out.
In addition, “MRI and CT scan equipment, as well as surgical equipment and expensive drugs in the operating room, are mostly products of multinational companies, so most of them go overseas when receiving medical expenses from Korean hospitals.” Multinational companies take it.”
“Although Kimlia’s appearance is nice, it gave me a big homework of cost,” he said. “Expensive medicines and scary medicines as collateral for life have emerged, and now, a forum for public debate has opened where we have to consider regulations on insurance and industry, etc.” I gave it a meaning.
Accordingly, “At this opportunity, we need to reconsider the regulations so that hospitals, universities, and researchers can actively research,” he said. “In the short term, we have to take care of the dying lives through health insurance, but in the long run, how do we do this? It was given the homework whether to solve it, and an external factor that could change Korea’s regulation academically and scientifically,” he emphasized.
Furthermore, he said, “The world is scared because a multinational pharmaceutical company with life as collateral has come in, and there is no choice but to provide insurance,” he said. “It is time to think about how to solve it wisely in the long term, and the most desirable thing is our country. He stressed that a virtuous cycle should be created by creating a structure that can be solved in Korea (so that treatment costs can be invested in Korea again).
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