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- 2026-04-21 15:18:21
- InterView
- KYMRIAH, a good but expensive medicine
- by Eo, Yun-Ho Nov 04, 2021 05:56am
- The cost of a single injection is 500 million won, but the era has come when cancer can be expected to be cured with that "once." Ultra-high-priced, high-tech new drugs are already approaching us. Kymriah (Tisagencleucel), a CAR-T treatment called dream anticancer, is the new drug. Kymriah obtained approval from the MFDS in March as the first treatment of the Advanced Regenerative Bio Act. Kymriah dramatically improved the survival period of patients with recurrent and refractory end-stage blood cancer, who no longer had treatment options available with a single treatment, and even confirmed the possibility of long-term survival. ◆The essence of process-customized treatment required for each patient Kymriah is an innovative personalized one-shot treatment that utilizes the patient's immune cells, and is an anticancer drug with all the characteristics of cell, gene, and immune treatments. As it is a non-reimbursed treatment, it is different from previous treatments from the mechanism and manufacturing process of manufacturing. First, the patient's immune cells are extracted. Afterwards, a receptor that recognizes cancer cells is inserted into the cell surface to form a cell with strong power, that is, a chimera antigen receptor, and injected into the patient. Kymriah's indication is ▲the treatment of adult patients with recurrent or refractory diffuse large-B-cell lymphoma (DLBCL) after two or more systemic treatments and ▲ the treatment of post-transplantation recurrence or secondary recurrence and subsequent recurrence or refractory B-cell acute lymphocytic leukemia (B-ALL, B-Acute Lymphoblastic leukemia) in children and young adult patients under the age of 25. The number of DLBCL and B-ALL patients who refused or recurred to existing treatment was about 200 in Korea, and until Kymriah's approval, there were no alternative treatment options or standard treatment was not established, so life expectancy was only 6 months. In fact, the median survival period of DLBCL patients who failed secondary treatment in Korea is around 4.73 months, and about 70% of patients who failed secondary treatment repeatedly perform rescue chemotherapy. The Kymriah permit presented patients who were no longer in need of treatment with another hope for long-term survival. According to clinical trials in patients with recurrent or refractory DLBCL, the overall response rate in patients administered Kymriah was 53%, of which 39.1% reached complete remission. In addition, in the case of clinical trials in patients with recurrent or refractory B-ALL, 8 out of 10 patients (82%) reached complete response (CR), and 98% of patients who reached remission were negative. ◆ In Korea, more than 5 cases were administered. Kymriah Center was established Kymriah is still a non-reimbursed drug and it is difficult to say that sales have been activated in Korea. However, preparation work for prescription is active. In particular, Big 5 advanced general hospitals are moving rapidly. According to related industries, Big 5 general hospitals, including Seoul National University Hospital, AMC, Seoul St. Mary's Hospital, and Sinchon Severance Hospital, are undergoing management approval procedures such as human cells, and Samsung Medical Center has already completed approval. Among them, in the case of Seoul National University Hospital, Kymriah (Tisagenlecleucel) passed the Drug Commission (DC) in April, and Samsung Medical Center also began prescriptions in May. Novartis, a developer of Kymriah, allows to pay by establishing a general hospital and Kymriah center. Kymriah Center will open in May at Samsung Medical Center and Seoul National University Hospital, respectively, and the rest of the upper-level hospitals are expected to join the center later. In order to establish a center, hospitals must obtain permission for management businesses such as human cells under the newly established Advanced Regeneration Bio Act, which means that medical institutions are actively working on preparing all matters. according to the Dailypharm, more than five Kymriah doses have already been made, even though they are non-reimbursed, and 10 prescriptions will be made within this year. The era of CAR-T is certainly beginning. ◆The insurance benefit registration procedure is also an issue Kymriah's insurance benefit registration is also an issue. It is unusual for interest in one drug to increase to this extent because it is such an expensive drug and there are so many patients waiting. In March, the drug was approved by the MFDS using the Drug Approval-Benefit Linkage System. And it was first introduced to The HIRA's Cancer Drugs Benefit Appraisal Committee in September, but was put on hold. When the results were released through the media, the leukemia association criticized the government and pharmaceutical companies in a statement. The patient association earlier criticized Kymriah for the delay in the proposal of the Cancer Drugs Benefit Appraisal Committee. Eventually, Kymriah passed the Cancer Drugs Benefit Appraisal Committee in October. It is encouraging to pass this deliberation, but there is a high possibility that there was a burden as it was so focused on attention. Novartis' Korea subsidiary's plan to share finances and its willingness to persuade its headquarters are expected to be key. Kymriah, a drug that is too good but too expensive, is just the beginning.
- InterView
- Patients with severe diseases don't really like Mooncare
- by Lee, Jeong-Hwan Oct 28, 2021 05:59am
- Health insurance authorities should recognize that as universal health and welfare increases the coverage of mild diseases, the access to drugs for severely rare and intractable diseases is greatly reduced. It is nonsense that policies to strengthen coverage such as herbal medicine benefits are implemented without economic evaluation today, when there are many serious drugs that cannot be reimbursed due to the adequacy of benefits." This year's parliamentary audit of the National Assembly's Health and Welfare Committee also dealt with the issue of accessibility to patients with ultra-high-priced one-shot treatments, which cost hundreds of millions of won per dose. Technologies for treating severe rare and intractable diseases such as cancer and autoimmune diseases are rapidly developing, but health insurance finances for benefit-applied drugs are not keeping up. On the 27th, Dailypharm met Professor Lee Hyung-ki (57), a professor of clinical pharmacology at Seoul National University Hospital, and asked about the direction of Korea's health insurance benefit system for expensive drugs. Professor Lee Hyung-ki said the so-called "Moon Jae In Care" implemented by the current government is not welcome at all to patients with severe rare and incurable diseases. While it is strict for drugs developed by global pharmaceutical companies or domestic pharmaceutical companies, it is unreasonable to enter the insurance right without any problems. Professor Lee said the government should adopt a selective differential welfare method. The basic direction for the government is to focus on expanding the benefits of ultra-high-priced treatments that are inaccessible even with average or high benefits, leaving treatments or diagnoses for mild diseases that can be spent on average annual income. According to a survey of 787 domestic companies by Job Korea, the annual salary of new college graduates this year is 41.21 million won for large companies and 27.93 million won for small and medium-sized companies. According to the analysis of business reports by each company of the top 100 companies in market capitalization, the average annual salary of employees of large companies is 83.22 million won. In addition, this year's average annual salary for small and medium-sized workers is 28 million won for employees and 57 million won for managers. Professor Lee points out that it takes about two years for one new drug to enter the benefit range, although the government claims to be completing the benefits evaluation about 300 days. Professor Lee said, "In the case of anticancer drugs, it takes about two years to receive health insurance benefits. In this case, pharmaceutical companies that have developed treatments and patients waiting for insurance will suffer from double regulations, he explained. Professor Lee added, "Since we mainly focus on price control, it becomes difficult to be reimbursed and patient difficulties increase." Asked by a reporter if it would be difficult to apply new drug insurance benefits that did not take into account health insurance finances at all, Professor Lee said, "There are too many policies such as herbal medicine benefits to put health insurance finances as a justification." Professor Lee criticizes that health insurance benefits are often made without standards or principles in areas that are difficult to accept from the perspective of new drug development pharmaceutical companies and severely ill patients. Professor Lee said, "The ultra-high-priced drug itself is, in the end, an innovative drug. Patients who have been confirmed to be effective will have an experience of changing their lives and not losing their lives. "Kymriah treatment costs hundreds of millions of won. It is a level that individual patients cannot bear, he pointed out. Professor Lee said, "The national health insurance funding alone will inevitably reach the limit of the medical insurance drug cost support system." Professor Lee said, "It is necessary to consider raising a third fund and financial source. The government should show leadership to expand fiscal sources, he said. Professor Lee also criticized the lack of economic evaluation tools for ultra-high-priced one-shot treatments. There is no additional system other than RSA, and ICER are too low. Professor Lee said, "I understand that the benefit evaluation tool has become more flexible than before. The problem is that health insurance authorities rely only on ICER. In particular, if the standard treatment is already expensive, no matter how innovative the new drug is, accessibility will not increase, he stressed.
- InterView
- Merck will “focus on specialty care capabilities"
- by Eo, Yun-Ho Oct 21, 2021 05:14am
- Javed Alam, General Manager of Merck Biopharma Korea The global chemical and pharmaceutical company Merck is working intently to strengthen its capabilities in the pharmaceutical sector. The company, whose main areas of expertise are liquid crystal and LED, has also been continuing its commitment to introduce new drugs, starting with the anticancer drug ‘Erbitux (cetuximanb),’ the immune-oncology PD-L1 inhibitor ‘Bavencio (avelumab)’ that was co-developed with Pfizer, to the recently approved multiple sclerosis treatment 'Mavenclad (cladribine).’ Dailypharm met with Javed Alam, the General Manager of Merck Biopharma Korea, who has celebrated his 2nd year at the company, to hear about Merck’s vision in the healthcare business. -You have spent most of your time here since your appointment in the COVID-19 pandemic. Could you tell us about your impressions and thoughts about your work here in Korea, and the achievements that were made?. I would have to say my time here was crisis after crisis due to the COVID-19 pandemic. However, despite the COVID-19 pandemic, we were able to protect our employee’s health and safety while continuing communication with our customers and ensuring a smooth supply of products for our patients, based on which we achieved business growth during the past 2 years. In the midst of the COVID-19 crisis, our company had focused on Specialty Care and efficiently reorganized the organization, and carried out our roles smoothly so that there were no disruptions in the supply of our products. In addition, we made various efforts such as actively embracing the use of digital channels to communicate with our customers to frequently update them on the company’s situation. Also, I take special pride in the fact that no Merck Biopharma Korea employee has had COVID-19. -- New changes have occurred in the Pharma business area, such as the launch of new products. Does this mean the company is seeking a change of tone? Merck’s goal in global healthcare is to become a Global Specialty Innovator, under which Merck Biopharma Korea aims to become the most innovative specialty care company in Korea. To achieve this goal, the company had to undergo various changes in its business model, company structure, organization, etc. While making such changes, we also changed our corporate culture to focus on restructuring the business model to focus on specialty care and digitalization. Through these efforts, we expanded our digital channel from 1 to 8, including webinars, websites, and web meetings. Also, the company made various changes structure-wise, and these various efforts have fortunately paid off to benefit the company. -I can see the company’s strong commitment to specialty care. The Specialty Care unit covers rare and incurable diseases that are difficult to diagnose or cure. The number of patients and specialists for such diseases is relatively small, and that is why it is also an area that has the highest unmet need from patients. Among various areas of specialty care, Merck is focusing on 4 areas - Immuno-oncology∙Oncology, Neurology∙Immunology, Infertility, and Endocrinology. Erbitux has been showing good performance in our existing Immuno-oncology unit. In the recent KSMO Annual Meeting, & Conference we have presented the results of OPTIM1SE that demonstrated the drug’s clinical safety and efficacy in Korean patients. In addition, we have also released the immuno-oncology drug ‘Bavencio (avelumab)’ that was co-developed with Pfizer in our efforts to become a specialty care leader. Bavencio is a treatment for Merkel cell carcinoma (MCC) which is a rare and aggressive type of cancer that has a 5-year survival rate of 0-20%. I believe we were able to provide new hope to these patients with Bavencio. In Neurology∙Immunology, we have the multiple sclerosis treatment Mavenclad (cladribine). Multiple sclerosis occurs most commonly in women in their prime - 20s to 30s - causing difficulty in their life and treatment. However, Mavenclad’s innovative dosing and administration allows patients to only take Mavenclad for up to 20 days over 2 years, and then be free from additional dosing requirements for the other 2 years. -What kind of efforts have Merck Biopharma Korea made to advance Korea’s healthcare industry? We have been actively participating in clinical programs and global trials to increase Korea’s level of contribution and influence. Korea is involved in all of the 20 global clinical programs at Merck including its key 7 programs. By actively participating in R&D and the clinical stage, we are increasing our contribution to Merck’s portfolio and ultimately increasing Korea’s influence in the global market. Also, we have been making efforts to increase Korea’s contribution in earlier stage innovation. For example, we help promising startup venture companies in Korea to connect with Merck’s innovation program. The ‘Merck Accelerator program’ has supported a total of 12 companies worldwide until now, and ‘Inhand Plus,’ a Korean startup, was the first in Korea to be selected to receive benefits from the program. -Could you briefly introduce the company’s pipeline products that you plan to introduce in Korea in the future? Merck Biopharma Korea is striving to showcase innovation in all areas of its involvement, therefore, you can continue to expect innovative changes and products from us in the future. In the past, the company had depended heavily on primary care products. However, now, as the Global Specialty Innovator, we hope to become an unrivaled company in specialty areas. Our first goal is to maximize our Korean patients’ accessibility to the company’s excellent pipeline products. Merck Global Is focusing on enriching its entire pipeline, and we will continue our efforts to promptly and broadly introduce all the innovative solutions, products, and technology that is and will be developed by Merck to our patients in Korea.
- InterView
- "A tenure professor’s calling is in developing a new drug"
- by Sep 17, 2021 05:56am
- On August 24th, the Hemato-Oncology Department of the Eijeongbu Eulji Medical Center was busy preparing for its new occupant. Professor Dongwook Kim (60), who looked new to his office, was busy discussing matters with various visitors including the hospital employees. Although the center had opened less than 6 months ago, its Hematol-Oncology Department looked more vibrant than ever. Professor Dongwook Kim, one of the leading authorities in the field of Chronic Myelogenous Leukemia (CML), had joined Eijeongbu Eulji Medical Center of the Eulji University after serving 30 years at the Seoul St.Mary’s Hospital. During his term at Seoul St.Mary’s Hospital, Professor Kim had made many first-ever achievements. At St.Mary's Kim had led the research of the first targeted therapy, ‘Gleevec,’ and many other next-generation drugs, and had also led the study on ‘Supect,’ the only locally developed targeted therapy for CML. His focus on gene analysis, to identify the causes why patients show different treatment effects, had laid the grounds for Korea's treatment environment to advance into precision medicine. Kim's efforts paid off, and the Seoul St.Mary’s Hospital became the first hospital to establish a center specializing in blood disorders - the Catholic Hematology Hospital - at which Kim served as the founding director. Professor Dongwook Kim When asked about why he joined Eijeongbu Eulji Medical Center after achieving so much, Kim's answer was “to conduct more research for a longer period of time.” Kim talked about a professor he met at the International Society of Hematology conference. The professor, who was over 90, came to chair one of the discussion sessions with a cane in one hand. This had left a deep impression in Kim’s mind. Also, he said that there are professors over the age of 80 in the Leukemia Network, for which 35 experts around the globe meet every 5 years to establish the standard of care for CML. Unfortunately, the circumstances at St.Mary’s Hospital were unfit for a professor to continue researching for the rest of his life. In medical schools in Korea, professors generally retire from his/her university at age 65, and stays as a professor emeritus, then continues work at a different hospital for 5 years before retiring. “As a director, I’ve watched many of my seniors retire. These able professors perform surgeries until the last day of their retirement. After 55 years of age, most professors experience reduced consultation hours and a lack of research labs. I also experienced this. My lab also saw a decline in funding and was on the verge of reducing our staff. In Korea, the government does not give government projects to professors over the age of 60. On the contrary, many senior professors over the age of 80 and even 90 take on research projects in Europe and the U.S. It is that different." With only 5 years left to retirement, Kim was also concerned about his patients, as they require lifelong treatment. Many patients asked professor Kim about his retirement plans. Those that were recently diagnosed showed the most concern. That was why Professor Kim started to consider seeking an environment where he can continue on his research without worries about retirement or lab reductions. And Eijeongbu Eulji Medical Center was the perfect place for Kim. “The Eijeongbu Eulji Medical Center promised full support and a stable environment where I could conduct research with my researchers for a long period of time. Thanks to such support, we are currently setting our new lab in the new building behind. We plan to sign MOUs with KAIST, UNIST, and Kwangwoon University and conduct joint research after my lab officially opens.” Professor Kim said, “We have already been planning various research projects. One is ‘Investigation on the single-cell dynamics related to the occurrence/recurrence of CML,’ which was selected as a research project by the government last year. The project aims to investigate the cause of CML and why the treatment effect differs in each patient." In other words, Kim and his team will attempt to find the cause of different treatment effects by analyzing the patient’s genes and the tens of thousands of cells in their blood. If the team discovers a gene related to leukemia, this may enable personalized treatment for each patient. This is what Professor Kim is investing most efforts in. Also, Kim is actively participating in the development of new drugs like ‘Supect’ in collaboration with bio ventures. Also, he had joined in the development of AI that can recommend appropriate treatment for each patient since 2 years ago. Kim plans to complete the government project within 5 years. Kim believes that the research will enable HCPs to discern which treatment is required for each patient according to their genes. Two new candidates were already discovered for new drug development. Also, the AI that Kim had started developing 2 years ago is now being tested in practice. After inserting all the characteristics of a patient from his/her age, gender, favorite food to genetic disorders, the program selects the most appropriate treatment among the 5 targeted therapies for CML, then recommends further measures according to each patient’s treatment response and side effects such as dose adjustments or discontinuation and switching. The goal is to be able to completely replace experts in the field. One of the questions I encounter most often during lectures is on ‘What drug to select.’ We aim to build an AI that can provide a perfect answer to that question. We are formulating the increase in speed, degree, grade of cancer cells to predict which patients will experience recurrence and how fast. This will allow us to predict how likely a patient may discontinue treatment within 5 years.“
- InterView
- Leclaza’s ESMO data will determine FDA approval
- by An, Kyung-Jin Sep 15, 2021 06:11am
- Cho Byung Chul, a professor at Yonsei University "This data will be the basis for determining the approval of Leclaza combination therapy. Following Tagrisso, the world is paying attention to how much lung cancer patients who failed to treat platinum-based anticancer drugs will react. " Janssen, a partner of Yuhan, will announce new clinical data on combination therapy with Leclaza at the ESMO 2021 online academic event, which will open on the 16th (local time). It is the very combination that excited the society (ESMO 2020) a year ago with an incredible number of "OR 100%." In the meantime, Leclaza's combined drug, Rybrevant, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-small cell lung cancer accompanied by 20 insertion variations of epithelial cell growth factor (EGFR). What synergy effect will Leclaza and Ambantamab have this year? Cho Byung-chul, a professor of oncology at Yonsei University, emphasizes, "We should pay attention to the response rate (ORR) of Leclaza and Rybrevant combination therapy unveiled at ESMO 2021." According to the abstract list released by the society, the new data for Leclaza combination therapy this year is a clinical study of CHRYSALIS-2 (phase 1b). The phase CHRYSALIS-21b clinical cohort A study evaluates the OR of Leclaza and Librevant combination therapy in patients with EGFR targeted anticancer drug Tagrisso and EGFR mutant non-small cell lung cancer who do not respond to platinum-based anticancer drugs.It is a thoroughly designed study to obtain permission for Leclaza and Librevant combination therapy in patients with Tagrisso resistance. According to Professor Cho, Taxotere is the only drug that can be used for patients under the current conditions. Taxotere is a cytotoxic anticancer drug that causes severe adverse reactions. Nevertheless, the reaction rate is close to zero (0%). In other words, they try because there are no other options, but it is virtually the same as there is no cure. It is predicted that early market sales will be possible through Breakthrough Therapy Design and acceleration approval. Considering the case of Librevant, which obtained the FDA acceleration review in May, it is judged that the possibility is sufficient. Recently, the American Society of Clinical Oncology (ASCO 2021), a combination therapy with Leclaza, also reproduced 36% OR in patients with resistance after Tagrisso treatment. Professor Cho said, "Lung cancer specialists who face patients in desperate situations in the clinic every day need a new treatment. This is why the world is paying attention to the ESMO announcement data, he explained. We are looking forward to the release of a treatment that can be used instead of 'Taxotere' as soon as possible, he said. Professor Cho is in charge of CHRYSALIS-1 multinational clinical trials, led by Janssen, evaluating Rybrevant alone and combined therapy. An intermediary study on the anti-tumor mechanism of Rybrevant in Exxon 20 mutant lung cancer was conducted to reveal the mechanism of anti-tumor effectiveness. Recently, it is evaluated as the leading player in leading the final FDA approval while leading the clinical development of Rybrevant. Rybrevant has not yet been approved in Korea, but it is conducting a program for patients with EGFR Exon 20 mutant lung cancer.
- InterView
- Treatment-free remission drug for chronic myeloid leukemia
- by Sep 07, 2021 05:53am
- The introduction of the world’s first targeted anticancer drug ‘Gleevec,’ has brought a revolutionary change in the field of chronic myeloid leukemia (CML) treatment. Patients who mostly died if they were unable to receive hematopoietic stem cell transplantation, may now not only survive long-term but can maintain a high quality of life and even discuss the possibility of treatment-free remission (TFR), where a patient can maintain a state of remission in their cancer cells even after discontinuing his/her treatment. Analysis shows that the possibility of TFR is determined by the response to the drug used in the initial stages of treatment. This means that patients with a higher rate of achieving an early molecular response (EMR, BCR-ABL1 (IS) ≤10%) at 3 months of treatment are more likely to be able to discontinue drug treatment in the future. And selecting an appropriate targeted therapy is of utmost importance in achieving such a high response in the early stages of treatment. Patients diagnosed with CML may select one of the 5 first-line treatments: the 1st generation drug ‘Gleevec (imatinib),’ the 2nd generation ‘Sprycel (dasatinib),’ ‘Tasigna (nilotinib),’ ‘Supect (ladotinib),’ ‘Bosulif (bosuinib).’ Each drug has a different method of intake, effect and side effects, and therefore a drug suited for each patient should be selected according to the patient’s characteristics. The Hemato-Oncology Professor Dongwook Kim of the Uljeongbu Eulji Medical Center, who is known as the authority in CML treatment, said, “We need to search for the best drug for each patient should be identified by monitoring the patient’s condition for around a year.” Kim added, “It is the ability of the doctor to tune the regimen while maintaining a treatment response. As compliance is crucial, choosing the right drug that fits each patient’s lifestyle, as well as appropriate medication education, is also very important." Dailypharm met with Professor Kim to hear about how to select the appropriate treatment for TFR in CML. Dongwook Kim, Professor of Hemato-Onocology, Uljeongbu Eulji Medical Center, Eulji University. -Discussion of treatment-free remission (TFR) has been ongoing in CML during the past few years. I believe patients would be very interested in achieving TFR. =Around half of the 2,200 patients I treat may take the drug discontinuation approach. Around 200 patients (that participated in clinical trials) have discontinued their drugs. The patient who had stayed off the drug the longest has discontinued taking medications for 17 years since 2004. His cancer cell level had risen and fell at a low rate and then turned 0 about three times in the first year, and has had no problem ever since. -If around half of the patients have the possibility of achieving TFR, that is quite much, isn’t it? =It is. And this is now possible due to the improvement of drugs. However, the important consensus on when and how the patients should be treated. has not been reached yet. Until now, patients who received drug treatment for at least 3 years and maintained their condition for at least 2 years, and showed a sustained molecular response (level of 0 in a genetic test) discontinued their drugs. We conducted a study on discontinuing Gleevec with the 2010-2015 patient data provided by the Ministry of Health and Welfare. Data showed that around 50% of the patients who received drug treatment for at least 3 years and showed genetic test results of 0 for at least 2 years relapsed. 2 patients have died from disease progression, and one patient is being treated using a different drug. Globally, around 1% of the patients who discontinue treatment may be at risk, and around half experience recurrence. Of course, most of these relapsed patients who receive drug treatment again become better. -Patients who have a white blood cell count of 10% or less at 3 months have the possibility of TFR. What factors contribute to achieving a good response in the early stages of treatment? =Prognosis differs greatly according to the drugs you select, so accurate drug selection is important. And patients experience a lot of side effects in the first 3 months of using anticancer drugs. Therefore, you cannot use the full dose during that period, and many patients discontinue or reduce their dose. The first three months are an important period in which treatment decisions may vary depending on whether patients respond or not respond to treatments as well as compliance. A treatment-naive patient can choose from one of five targeted anticancer therapies. In choosing the one treatment, all features of the patient’s character need to be from age, gender, food preference, to his/her family medical history. The patient may choose their treatment from the scope of the information they know. I will be presenting on ‘How I select targeted anticancer therapies in CML’ at the International Conference on Hematology and Blood Disease in October. -Could you tell us in more detail what needs to be considered in determining what drug is appropriate for which patient? =You could largely consider three things. What underlying disease does the patient have? I check for diabetes, high blood pressure, high cholesterol, etc. to account for the side effects of the targeted anticancer therapies. Each anticancer drug has different side effects, and using a targeted therapy that has the side effect of increasing one’s blood pressure may treat his/her CML, but would require separate treatment for diabetes. Some drugs from blood clots or raise the cholesterol level of a patient as a side effect. Also, age is important. In particular, the prevalence of leukemia increases with age, and patients may develop CML at 70. Cells also age with humans in the aging process, and blood cells die faster with age Therefore, whether to use the 2nd or 3rd generation drugs that have much potent effect over Gleevec becomes the question. For patients in their 70s, prolonging survival to 10 or 15 years with less potent drugs that have fewer long-term side effects may be more important than being fully cured. Genetic mutations are also an important consideration. However, how the mutations affect treatment was not clearly identified, so we use the ELTS score to predict the differences in prognosis, by low-risk, moderate-risk, and high-risk patients. If we can find a gene that can predict the treatment effect using next-generation sequencing, it would become an important biomarker in the treatment of CML. -Does that mean the first-generation treatment is better for the elder patients and second-generation treatment is better for the younger patients? =Yes. Compared to Gleevec, second-generation treatment is approximately 20 times, to even 325 times in the case of Sprycel, with varying side effects. Patients who use Sprycel long term may develop pleural effusion, a condition where water fills up in the lungs. Tasigna can increase the risk of blood clots in the heart and brain by 25% in 10 years, and by 10 times in the same age range. Supect can increase blood glucose levels. Tasigna and Supect have slightly more side effects, increasing glucose levels or cholesterol levels than other drugs. Therefore, older patients that use such drugs may develop arteriosclerosis and significantly increase the probability of developing myocardial infarction, cerebral infarction, or thrombosis. So if a patient has a family history of hypertension or hyperlipidemia, the use of the two drugs I mentioned should be ruled out. This is simply looking at the side effects, and we also need to consider the presence of additional chromosomal abnormalities, additional genetic mutations, and other factors of high-risk groups, to select the drug with the lowest risk of developing side effects for each patient’s underlying condition among the second-generation drugs. Therefore, prescriptions made by each doctor for the same patient may differ by doctor. In particular, hospitals with a low prevalence and incidence rate may tend to prescribe a particular drug. Hospitals like Uljeongbu Eulji Medical Center which has a large CML patient population may be better in the selection of drugs and treatment. For example, some patients of mine came from hospitals that rarely treat CML patients after failing treatment. And I sometimes wonder why they used that drug for the patient. Also, records show many failures to treatment where the appropriate dose was not used, etc. It may also be due to side effects from other drugs that the patients had originally taken. -Also, the doing regiment for each drug is also different. This may also affect the selection of treatment according to each patient’s lifestyle. =That is true. Sprycel is taken once a day, and Tasigna or Supect is taken twice a day. Tasigna or Supect is taken in an empty stomach, so it needs to be taken 1-2 hours before or after meals, but Sprycel does not have such limitations. It has better dosing convenience as it just needs to be taken regularly once a day. In particular, patients who work night shifts or work 3 shifts, like nurses, may have trouble taking a drug twice daily. Therefore, according to each patient’s occupation and lifestyle, one of the two options – of taking drugs once or twice – may be selected. It is already a wide known fact that taking the medicine correctly without skipping is good for treatment. Discontinuing a drug can develop tolerance to the drug, and reduce the treatment effect. This is more important for drugs that are taken daily. Therefore, such a method of administration may be a serious and even critical issue for some occupations. Dosing education has become increasingly important as drug compliance is a very serious issue. A European patient group, CML Advocate, surveyed tens of thousands of patients about drug administration, and only 70% of the patients responded that they took their medication as prescribed for three days in a month. 30% did not take the drug properly for over 4 days a month. Surprisingly enough, about 60% of patients have used and survived using Gleevec since its introduction. This is in line with the medication compliance rate. In this sense, compliance to treatment is very important and discussed often. In that sense, dosing compliance of Sprycel, which is taken once a day and can be taken with or without meals, is much higher than other drugs. -In other words, making the effort to find the optimal drug for each patient according to each patient’s underlying condition and lifestyle is the most important process? =That is right. If someone asks when should we search for the right drug, I would say 1 year. I tell my patients that I would be tuning the dose for the patient while monitoring their response and side effects. It is the ability of the doctor to tune the regimen while maintaining a treatment response. And that difference is what makes one doctor more skillful than the other. One of the most frequently asked questions in lectures is what drug I would choose. And I always say, ‘There is no one drug that is best for all patients.’ We need to find the best drug for each patient.
- InterView
- “Olumiant provides rapid AD symptom improvement"
- by jung, sae-im Aug 06, 2021 06:04am
- The introduction of JAK inhibitors in the field of moderate-to-severe atopic dermatitis (AD) treatment was like a welcome rain in the drought of treatment options in AD. In 2018, the approval of the biologic agent ‘Dupixent’ transformed the AD treatment paradigm, however, many patients still feel an unmet need existed due to the limited reimbursement conditions and high drug price. JAK inhibitors are expected to widen the scope of treatment options for AD patients with features different than those offered by Dupixent. The first JAK inhibitor to receive approval for the AD indication was Eli Lilly’s ‘Olumiant (baricitinib)’ The treatment effect and safety of Olumiant were identified in the three clinical trials - BREEZE-AD1, BREEZE-AD2, BREEZE-AD7 –as a monotherapy and combination therapy with a topical corticosteroid (TCS) in adult patients with moderate to severe AD. In particular, Olumiant rapidly improved itching that severely deteriorates the quality of life from Day 2. Professor Sang Wook Son (Department of Dermatology, Korea University Ansan Hospital), who has been prescribing Olumiant from the clinical stages said, “Olumiant will play an important role in improving the symptoms and quality of life of patients. The various new drugs that have been introduced to the AD treatment environment have brought a ‘revolution’ to the AD treatment environment.” Dailypharm met with Professor Son to hear about the adult atopic dermatitis treatment environment and the role of Olumiant in Korea. Professor Sang Wook Son -Clinical trials on Olumiant have shown that it rapidly improves symptoms from the second day since its first administration. What does this mean for moderate to severe AD patients?” = For AD patients, managing pruritus, or itching, is very important. However, this symptom was difficult to control, as the inflammatory response or immune response, which are mechanical aspects that cause itching, are difficult to control. We use immunosuppressants and antihistamines for pruritus treatment, but it was difficult to expect dramatic effects with these treatments. This lack of a rapid and effective treatment option for severe itching had made treating AD patients quite difficult, and Olumiant’s data on its rapid effect was the most awaited aspect of the new drug. I have been experiencing this rapid symptom improvement effect of Olumiant in clinical practice, and believe this feature will continue to be one of the greatest strengths of Olumiant. - Olumiant’s oral formulation is also considered beneficial. For which patients would the oral Olumiant tablet be appropriate? =According to Olumiant’s indication, patients with moderate to severe AD, in other words, those whose Eczema Area and Severity Index (EASI) score is between 16-23 or over may use Olumiant. However, as there is only little experience accumulated in the actual clinical field with Olumiant, there is still no consensus or guideline on which treatment should be used for which patient. However, Olumiant has the benefit of being easy to carry as an oral formulation. Patients may conveniently carry around and take Olumiant from their bag according to their dosing schedule. Also, they can flexibly apply doses, reducing the dose or taking a resting period when symptoms improve. Also, patients who fear needles would also prefer oral forms of treatment. -AD is a chronic disease that requires long-term use of treatments. Therefore, the safety of long-term administration is also an important aspect in selecting treatments. I heard there were safety concerns in using JAK inhibitors. How about Olumiant? =Olumiant has around 7 years’ worth of long-term safety data accumulated in the field of rheumatoid arthritis. No special adverse events were identified as an issue during that period. Based on these results, there are expectations that Olumiant will have fewer side effects than existing treatment options not only in clinical studies but also in actual clinical settings -Olumiant can be administered alone or in combination with a topical corticosteroid (TCS) =Combination therapies are considered a sort of principle in AD treatment as it requires the use of TCS and other topical immunomodulators to achieve full effect. In particular, data has shown that the efficacy of treatment improves when using Olumiant with TCS in AD. -What role do you expect Olumiant will play in the treatment of adult AD? = I felt more confident treating patients after Olumiant was added as an AD treatment option. Compared to existing treatments, Olumiant has little burden of safety has a positive therapeutic effect. As patients can experience dramatic changes in various aspects including treatment satisfaction, improvement of quality of life, and improvement of itching and lesions, I have high expectations for Olumiant's role in the field of AD treatment.
- InterView
- MSD "Will care for employees and new drug reimbursement"
- by Eo, Yun-Ho Jul 13, 2021 12:59am
- Keven Peters, Managing Director at MSD KoreaApart from its positives and negatives, MSD (known as Merck in the U.S.) is a company apt at ‘adaptation.’ MSD, which first cut its appearance in circulatory, respiratory drugs, and vaccines, became a leader in the field of diabetes in the 2000s with the introduction of its Januvia(sitagliptin), a DPP-4 inhibitor. In 2010, MSD became a sensation with the release of its PD-1 inhibitor ‘Keytruda(pembrolizumab),’ marking the start of the era of cancer immunotherapies. MSD’s forward-looking eye that allowed for the launch and success of various first-in-class drugs regardless of the disease area, is an undeniable strength of MSD. However, MSD had also been in the throes of change from the adaptation process. Last year, the company had officially announced the completion of its spin-off of Organon. In the process of the spinoff, MSD suffered considerable labor-management conflict. Also, MSD is in a 3-year back and forth with the authorities regarding the reimbursement expansion of its lead product Keytruda to first-line treatment in lung cancer. Amid such change, MSD Korea had welcomed a new head to its office in November last year. Keven Peters, the new Managing Director at MSD Korea, who has come to head the Korean subsidiary after serving in the Thailand subsidiary, had jumped in to resolve the pending issues, signing a collective agreement with the union and holding meetings with the government to allow for the reimbursement of Keytruda. Dailypharm met with the new Managing Director Kevin Peters to hear about his seven months in office. -You have been very busy since you took office. Let’s first discuss the labor-management conflict issue. What efforts have you made to resolve the conflict that arose in the spinoff process? As you know, we have signed the 1st collective agreement in January. I am proud that we were able to reach a mutual agreement after close discussions with the labor union. Also, I plan to visit our 4 local offices in Daegu, Gwangju, Daejeon, and Busan to communicate with the employees there starting early July. I will be sharing the company’s stories there and will hold an ear out to what our local employees have to say on each matter. Also, I plan to humbly take the advice that they may have to offer. My top priority is to have employees take an interest in our company and engage them in company activities. I am doing my best to listen to what all our stakeholders have to say. -You should be quite well-read on Korea’s drug pricing policy due to the situation with Keytruda. What do you think about Korea’s policy? From my 7 months of experience here, I felt that the HCPs and the government in Korea have a strong will to reimburse drugs. Of course, there’s the wish that reimbursements could be discussed more quickly. As you know, we are in the process of discussing increasing the accessibility of Keytruda. With lung cancer patients in 52 countries around the globe already using Keytruda as first-line therapy, I hope that our Korean patients can also have improved access to the drug as soon as possible. Increasing accessibility of Keytruda is an issue for consideration for all governments around the world. I think it is important for the key stakeholders including the government, companies, and HCPs to cooperate and collaborate to find a better way to increase the accessibility of the drug. -It seems that you have some regrets regarding the ‘quickness’ of the reimbursement approval process in Korea. In fact, reimbursement discussions for Keytruda first-line have been ongoing for over 3 years now. Efforts both ways, not only the government but the company’s efforts, are also required for a successful resolution of the issue. And as you know, there have been many arguments over the inadequacy of the cost-sharing plan that was proposed by the company. What I can promise now is that MSD will continue to cooperate with the government and healthcare officials to ensure that our patients can receive the optimal treatment. The company has submitted a financial sharing plan to the Review Committee for Cancer Diseases that proposes an unprecedented level of cost-sharing by the company, based on which we hope to see progress in Keytruda’s reimbursement expansion within a few weeks. -From what I know, the global investment in Keytruda is nearly 15 trillion won. Domestic investment (15 billion won) seems to be small in comparison to the global amount invested. MSD Korea is ranked no.1 in terms of R&D investment size in the MSD Asia-Pacific region. Our number of new clinical trials approved in Korea over the past four years was at a leading level among multinational companies, and the amount invested in R&D last year increased by 66% compared to the previous year. Quality data and infrastructure are key considerations used for making investment decisions in rclinical research. Korea owns excellent resources in this regard. We are continuously looking for institutions to collaborate with in Korea, and plan to further expand our collaboration in the future. In particular, an unprecedented number of clinical trials are underway in the field of oncology. There are 1,400 clinical trials in the world related to Keytruda, of which more than 900 are combination therapy studies. -What other products do MSD Korea plan to introduce in Korea? I cannot share specificities regarding releases of drugs before their approval, but we are preparing to introduce a chronic cough treatment, HIV treatment, antibiotic, and pneumococcal vaccine among others. Also, a Phase III trial is ongoing for our oral antiviral ‘molnupiravir’ that is expected to contribute to bringing an end to the COVID-19 pandemic. Also in the mid-to-long term, we own an extensive portfolio ranging from PARP inhibitors, VEGF TKIs, HER2 TKIs, antibody-drug conjugates (ADCs), to antibiotics.
- InterView
- Takeda, “Alunbrig improved both OS and QoL”
- by Jul 08, 2021 05:58am
- Medical Science Liaisons (MSLs) in Medical Affairs of pharmaceutical companies act as a ‘bridge’ between healthcare professionals and companies. They gather the unmet needs of HCPs and establish strategies for new drugs to address such needs. MSLs also deliver academic data and expertise based on clinical grounds in compliance with local regulations to HCPs, patients, and internal employees. Competition has been fierce in the non-small cell lung cancer treatment market, particularly the ALK targeted therapy market, with the introduction of various new drugs. The market is moving on from the one-and-only 1st generation treatment, Pfizer’s ‘Xalkori,’ to 2nd generation products. By order of entry, three 2nd gen products - Novartis’s ‘Zykadia (ceritinib),’ Roche’s ‘Alecensa (alectinib),’ and Takeda Pharmaceutical’s ‘Alunbrig (brigatinib)’ – have entered the market. Among these, Roche and Takeda’s products are in the fiercest competition. The role and responsibility of MSLs in charge of these products have also increased. Dailypharm met with Bokyung Kim, MSL at Takeda Pharmaceuticals Korea’s to hear about the ALK-positive NSCLC treatment market, its unmet needs, and the role and strategy of Alunbrig in this market. Bokyung Kim, MSL at Takeda Pharmaceuticals Korea -Could you give us a brief introduction about yourself and your role in Medical Affairs of Takeda Pharmaceuticals Korea? = SInce entering Takeda Pharmaceuticals Korea as an MSL in October last year, I have been in charge of Alunbrig for 9 months. I meet with healthcare professionals to identify the unmet needs in the field to establish strategies based on the demand. In the company, I discuss with various business divisions to set the direction for Alunbrig and prepare the necessary medical grounds so that our drug can contribute to resolving the unmet needs in the field. In the past, the Medical Affairs division mainly performed tasks to support other business divisions in the company, however, perception of the role of our department has started to change around 10 years ago. Medical Affairs now develops core strategies for new drugs, serving as a bridge between various business units as well as research and development. Also, the unit provides academic data and expertise to internal and external stakeholders in an objective and fair manner in compliance with the local code of medical ethics and regulations and provides academic advice. -At the time Alunbrig was introduced to Korea, other ALK-targeted therapies were already in the domestic market. Were there any difficulties due to this late entry? =Other treatments that were released before Alunbrig have brought treatment benefits to patients, however, unmet needs still existed in various areas, ranging from treatment effect, adverse events, quality of life, to convenience in administration. I believed that the introduction of Alunbrig could bring new treatment benefits that existing treatments were unable to provide. -What unmet need still remains due to characteristics of ALK-positive NSCLC in Korea? =ALK mutation occurs in around 4-5% of all NSCLC patients and occurs more commonly in women and Asian patients. Also, it is found more frequently in non-smokers compared to other NSCLCs and affects a relatively younger population in their 50s to 60s. Therefore, in addition to data on survival such as progression-free survival (PFS), other factors such as tolerance, medication adherence, and quality of life should also need to be considered collectively. The biggest unmet need in the treatment of ALK-positive NSCLC lies in brain metastasis and tolerance. This patient population has a higher risk of brain metastasis than other lung cancer patients. How long a drug can delay brain metastasis, and how effective the drug is in patients with brain metastasis must be considered. Also, people may have developed tolerance to TKI targeted drugs, therefore, how effective the drug is in such a population is also an important consideration. -With Alunbrig approved for insurance benefit in April as a 1st-line therapy, all ALK-targeted drugs introduced to Korea are now available with reimbursement from 1st line. What strengths does Alunbrig have over other ALK-targeted therapies with regards to its mechanism of action? How effective was the drug in patients with brain metastasis in clinical trials? =Unlike other existing treatments, Alunbrig was developed into a unique U-shaped platform. This structural design allows the drug to bind more strongly to the ATP attachment site that is used as an energy source when activating the ALK gene. In a preclinical trial, the drug selectively bound to ALK mutant variants to act stably in the body. Furthermore, Alunbrig demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus Xalkori, the existing first-line treatment option, in the Phase III ALTA-1L trial. In particular, in the second interim analysis, Alunbrig demonstrated superior clinical efficacy over Xalkori in the first-line setting regardless of brain metastasis in all ALK-positive NSCLC patients. Also, Alunbrig demonstrated a differentiated PFS improvement compared to Xalkori from early on in patients with brain metastasis that are difficult to treat. In addition, Alunbrig significantly reduced HR compared to Xalkori, to 0.25. So far, the data presented from the ALTA-1L trial only covers up to a two-year follow-up study by June 28th of 2019. We expect to see longer survival data when the final results are released soon. -Compared to other drugs that conducted investigator-assessed trials, the ALTA-1L trial was designed closer to the real world with BIRC-assessed endpoints. Why did the study choose to use BRIC-assessed results, which would have brought out more conservative results? =According to FDA guidelines, review from an independent evaluation committee can minimize bias. This is not essential in randomized, blinded clinical trials, however, as chemotherapy is often the standard treatment in cancer treatment, comparing this with oral anticancer drugs in a blinded trial is realistically not possible. This is why the trials are designed as open-label trials, in which case, BIRC assessment is required. We used BIRC-assessed primary endpoints according to the guideline recommended by the FDA to increase the objectivity and fairness of our trial. -How does Alunbrig affect patients with regards to their quality of life? = ALK-positive NSCLC occurs commonly in the socially active 50s. Therefore, studies on Alunbrig assessed the improvement in quality of life in addition to the drug’s efficacy. Assessed with the representative tool used for quality of life in cancer patients, EORTC QLQ-C30, the Alunbrig arm maintained the quality of life without worsening for 26.7 months vs. Xalkori. Also, convenience in administration is also an important factor to consider in long-term treatment. Many studies on long-term treatment experience from chronic diseases among others have shown that convenience in administration is very important for the quality of life and prognosis of patients. Alunbrig’s 1 tablet once daily administration is expected to contribute to the improvement of quality of life in these patients. *Dose and schedule of first-generation Xalkori is 1 tablet taken twice daily. Zykadia is taken in 3 capsules once daily, and Alecensa is taken in 4 capsules twice daily. -How was Alunbrig received in the field after being approved for reimbursement as first-line? Some have said that Alunbrig and Alecensa have similar efficacy in patients with brain metastasis. What is your view on this? =Alunbrig was positively reviewed by HCPs since being reimbursed as second-line treatment due to its good treatment effect in patients. With its reimbursement expanded in April, doctors have highly rated the drug as a new treatment opportunity for patients with an unmet need and for those who saw unsatisfactory effects from existing first-line therapies. Expectations were high as Alunbrig had shown high clinical effects in patients, but they were also highly satisfied in terms of convenience in administration. Also, the company’s efforts to promptly approve and reimburse Alunbrig in Korea as soon as it was approved as a first-line in the U.S. were positively received. Alunbrig and Alecensa have both shown better effects than Xalkori in clinical trials on patients with brain metastasis. We cannot directly compare the two drugs due to a lack of head-to-head study, however, patients should consider various aspects in addition to treatment effect, such as tolerance and convenience in administration when selecting their treatment. -Some patients hesitate using Alunbrig due to its pneumonia adverse reaction. =In the field, clinical practitioners have deemed that the symptoms after administering Alunbrig were similar to pneumonia, but is an EOPE (Early-Onset Pulmonary Events) that occurs temporarily. In some patients, symptoms similar to pneumonia may appear temporarily, but when the symptom is resolved early on, the symptom has the characteristic of not occurring again during the period of administration. Also, clinical experts in Korea have also said that EOPE symptoms are reversible adverse reactions that are fully manageable and can be quickly recovered.
- InterView
- Leclaza's ASCO data is like a global champion
- by An, Kyung-Jin May 28, 2021 06:08am
- Cho Byung-chul, a professor at Yonsei UniversityThe response rate for 'Lazertinib+Amivantamab' is the same as when ESMO was announced? It's ridiculous. The data is incomparably more complete than it was 7 months ago. " Professor Cho Byung-chul (oncology at Yonsei Cancer Hospital) commented on Leclaza (Lazertinib) combined data. A number of questions have been asked since the opening of the American Society of Clinical Oncology (ASCO 2021) and some misinterpretations need to be corrected. Professor Cho will introduce the latest clinical results related to combined therapy of Leclaza and Amivantamab at the ASCO 2021 online conference on the 5th of next month. This is the follow-up announcement of CHRYSALIS 1b, which drew much attention at the European Oncology Society (ESMO 2020) last year. The purpose is to evaluate the response rate of 'Lazertinib+Amivantamab' combined therapy in patients with resistant non-small cell lung cancer. The published objective response rate (ORR) is 36%. Fifteen out of 45 Tagrisso-resistant patients reached a partial reaction (PR) that reduced the tumor size by more than 30%, and one showed a complete reaction (CR) that completely disappeared. Because ORR figures are the same as when ESMO 2020 was announced, it can be accepted as the same data. "Even if the ORR values are the same, the maturity of clinical data has completely changed," Professor Cho added. The key is the difference in follow-up periods. Data released at the time of ESMO showed a follow-up period of only about four months after medication. On the other hand, the tracking period of ASCO's announcement increased to 11.8 months. In other words, the same response rate was maintained even though the tracking period has more than doubled.The duration of the reaction in patients who responded to the drug administration was more than 10 months. When the concept of biomarker is combined, the reaction rate increases further. Eight out of 17 patients with EGFR and MET mutations, known as Tagrisso's most common cause of resistance, showed treatment responses, achieving ORR 47%. However, the absence of biomarkers does not mean that the response rate is low. Of the remaining 28 people whose biomarkers were not identified, eight showed tumor responses to combined Lazertinib+Amivantamab administration. In terms of ORR, it is 29%. "There is a group of patients who are good at responding to Lazertinib+Amivantamab combined therapy," Professor Cho said. "However, the data alone when there is no biomarker is far more competitive than the existing treatment." Previously, there were no lung cancer treatments that demonstrated a 30% response rate and a duration of 10 months in patients who failed Tagrisso treatment. For example, the most prescribed combination of Tagrisso and MET inhibitor Savolitinib is 30% response rate and 7.9 months response duration when only MET patients are selected. Professor Cho compared this data to boxing. It's nothing short of winning Mike Tyson.Treatment of non-small cell lung cancer, which has developed new resistance after Tagrisso administration, is quite difficult due to tumor heterogenicity. This means that the data has increased over a long period of tracking for cancer patients with such malignant conditions. Professor Cho said that there is a good chance that Lazertinib+Amivantamab combined therapy will be designated as a U.S. FDA innovative therapy (BTD) within this year. If similar levels of data are reproduced in Janssen's ongoing CHRYSALIS-2 clinical trial, FDA approval will not be long.
