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- 2025-12-17 17:11:40
- InterView
- Restoring confidence post-Invossa incident was my priority
- by Kim, Jin-Gu Jan 10, 2024 05:42am
- “Even in the face of failure, do not worry. As the CEO of the company, I will take full responsibility for everything. We will engage in frequent communication. Once we reach a consensus after thorough discussions, I will bear responsibility for the outcome, regardless of the outcome.” In his inaugural speech in March of the previous year, the newly appointed CEO, Kim Sun Jin, of Kolon Life Science sent the message to the executive and staff members. Kim dedicated a year of relentless efforts toward enhancing the corporate mood after assuming the leadership position at Kolon Life Science. Kim Sun Jin, CEO of Kolon Life Science CEO Kim became affiliated with Kolon Life Sciences after joining Kolon TissueGene as an independent director in March 2020. At the time, both Kolon TissueGene and Kolon Life Sciences were heavily affected by the Invossa incident. About ten months before his joining, the U.S. Food and Drug Administration (FDA) issued a clinical hold on Invossa in May 2019. The clinical hold was lifted in April 2020, however, the clinical trials in the United States were unable to resume immediately. Patient enrollment was significantly hindered by the Covid-19 pandemic. Further complicating matters, the clinical reagents sent to the Contract Manufacturing Organization (CMO) were inadvertently contaminated with foreign substances. Faced with one challenge with another, CEO Kim, serving as a Chief Medical Officer (CMO) of Kolon TissueGene, committed himself to resolving the problem. Subsequently, the Phase 3 trials for the drug resumed a drug administration in Dec. 2021. Kim is recognized for his pivotal role in successful resumption of Phase 3 U.S. trials for Invossa (current project name: TG-C). Although the U.S. trials resumed, the overall corporate mood remained depressed. Recognizing this, Kim stressed the saying ‘Even in the face of failure, do not worry.’ in his inauguration speech. "After the Invossa incident in 2019, Kolon Life Science experienced a somewhat depressed corporate mood overall," Kim recalled. “When someone experiences failure once, the fear of failing again intensifies,” Kim added, “The setback deeply affected everyone. So, I consistently reassured them that what happened was not an individual's fault. I tried to help the members of the company heal from those wounds and rebuild their confidence.” In the 2nd year of joining, CEO restructures the company…”Reinforcing R&D and bringing synergy among the four companies” While focusing on reorganizing the company roles, Kim focused on instilling confidence. Kim placed particular emphasis on restructuring the research division. As part of this effort, research headquarters was established within Kolon Life Science on January 1st of this year, making it the first major organizational change since he assumed the CEO role. Previously, the company's research capabilities were split between bio- and chemical research, and now, these have been merged into one. Additionally, synthetic drug development has been strengthened. The analysis is that after restructuring, the focus is more on new drug development without differentiating between chemical and bio research. Kim evaluated that Kolon Life Science and associated companies have a perfect rotational structure. With Kolon Life Science in the center, Kolon TissueGene is responsible for new drug R&D and clinical development, Kolon Biotech manages production, and Kolon Pharma manages domestic distribution and sales of these products. It is intended to encompass the entire process from discovering new drug candidates to production, distribution, and sales. However, Kim expressed some reservations about the level of organic integration among these companies. Kim believes that there is still room for improvement in utilizing the potential and capabilities of each company up to 100%. "After joining the company, I realized that, with the exception of Kolon Pharma, which is already normalized, other companies fell short," Kim remarked and added, "I focused on eliminating redundant functions across the four companies and internalizing as many R&D technologies as possible." Kim also announced that each company will specialize in R&D based on specific diseases and substances. The goal is to restructure and enhance the efficiency of R&D by allowing each company to maximize its unique expertise. "Just as a conductor leads an orchestra to bring out the unique talents of each musician, we will strive to create synergy among the four companies, allowing them to maximize their respective expertise in research and development, clinical development, production, and distribution," Kim remarked. “Invossa U.S. trials are nearing completion…In development with more stringent conditions” With the new organization, Kim’s goal is to successfully complete the clinical trials for Invossa (TG-C) in the short term and approach the commercialization of other candidate substances in the long term. For Invossa clinical trials, U.S. Phase 3 trials are nearing completion. The patient registration is closing. Industry experts predict that the trials will be near completion by early this year. Following the trial's completion and a subsequent two-year follow-up observation period, the company will be able to submit a Biologics License Application (BLA). “Invossa and TG-C are essentially the same substance,” Kim explained. “While there are minor differences in the volume and manufacturing of cells used in Korea and the United States, there aren’t any differences in the aspect of the safety and the efficacy.” “In cell and gene therapies, differences due to gender, age, or race are typically negligible. Therefore, the results from clinical trials conducted in Korea might be replicable in U.S. trials” Kim said. “I cautiously speculate that we can potentially achieve approval without significant difficulty.” However, having faced setbacks previously, Kim intends to stay vigilant until the very end. Therefore, the U.S. clinical trials will implement more stringent conditions. “For treatments targeting pain, external factors can influence the clinical outcome greatly. I wouldn’t jump to conclusion. We must stay focused until the completion,” Kim added. “While the overall clinical design is similar to that in Korean clinical trials, the U.S. trials are being conducted under more stringent conditions. To that extent, we are confident about these clinical trials,” Kim stressed. Kim elaborated that the development of other candidate products, in addition to Invossa, is actively progressing. Kim added that 'KLS-2031,' a potential therapeutic for radiculoneuropathy, is currently subjected to sub-group analysis with results from the concluded Phase 1/2a clinical trials in the United States. At the same time, non-clinical trials designed to expand indications are nearing completion. For 'KLS-3021,' a chemotherapy candidate currently in development, its indication was determined after additional non-clinical testing. The toxicity and distribution testing is in process prior to clinical trial entry. Kim, as an expert in clinical translation, emphasized the importance of innovative clinical trial designs. “A notable issue in the Korean pharmaceutical and biotech industry is the tendency to replicate clinical designs from overseas. I strongly oppose this approach. Instead, development of innovative designs optimized for candidate substances is needed,” Kim stated.
- InterView
- ‘RCC treatment should reflect international guidelines’
- by Son, Hyung-Min Jan 09, 2024 05:49am
- In-Keun Park, Professor of Oncology at Seoul Asan Medical Center The treatment paradigm for renal cell carcinoma has been changing with the emergence of immuno-oncology drugs, but the latest practice guidelines for the disease are not being reflected in practice in Korea. In-Keun Park, Professor of Oncology at Seoul Asan Medical Center stressed how treatment options for patients with recurrent renal cell carcinoma are limited. In the first-line treatment of renal cell carcinoma, immuno-oncology drugs have been approved and have been successful in improving survival rates. However, treatment options for recurrent patients remain limited. As renal cell carcinoma is often diagnosed at an advanced stage, it has a poor prognosis and a high rate of recurrence. Therefore, it is important to secure a variety of options for each line of treatment, but when looking at the currently available second-line options, there are fewer drugs available in the second-line than in the first-line. Professor Park stressed how securing treatment options for RCC after immuno-oncology drugs by referring to international guidelines can improve the survival rate of RCC patients in Korea. Introductino of immuno-oncology drugs for renal cell cancer change the treatment paradigm Professor Park believes that the introduction of immuno-oncology drugs has completely transformed the treatment paradigm for renal cell carcinoma. Currently, 4 treatment options that include immuno-oncology drug combinations are approved in Korea as a first-line treatment for renal cell carcinoma. ▲The combination of BMS's immuno-oncology drugs Opdivo (nivolumab) and Yervoy (ipilimumab); ▲combination of Opdivo and Ipsen's targeted anticancer drug Cabometyx (cabozantinib); ▲ combination of MSD's immuno-oncology drug Keytruda (pembrolizumab) and Eisai’s targeted anticancer drug Lenvima (lenvatinib); and ▲ combination of Keytruda and Pfizer's targeted anticancer drug Inlyta (axitinib) are available for the first-line treatment of renal cell carcinoma. The Immuno-oncology drug+ immuno-oncology drug and immuno-oncology drug+targeted anticancer drug combinations have increased survival in patients with renal cell carcinoma. However, in Korea, only the combination of Opdivo+Yervoy is granted reimbursement. Also, the insurance only covers treatment with the combination for two years. Professor Park said, “Immuno-oncology drugs are a game changer that transformed the treatment of renal cell carcinoma. Before, when the targeted anticancer drug Sutene (sunitinib) was the standard of care, patients with poor prognostic factors had a life expectant that did not last one year," He added, “In Korea, the Opdivo+Yervoy combination is the most commonly used, and its progression-free survival (PFS) often exceeds 1 year. However, the combination is only covered for two years in Korea, so it is difficult to predict the outcome after that." While it is possible for patients to treatment with immuno-oncology drugs without reimbursement, its cost is burdensome. For Opdivo alone, patients have to pay more than KRW 4 to 5 million a month as out-of-pocket costs. “Also, due to the limited reimbursed options in the first-line, patients are almost always forced to use the Opdivo+Yervoy combination. Major guidelines recommend the Opdivo+Cabometyx combination and the Keytruda combination for low-risk patients in first-line treatment, but these are difficult to use in the field due to their non-reimbursement." Limited reimbursed treatment options after first-line treatment Immuno-oncology drugs have been successful in improving survival in first-line renal cell carcinoma, but treatment options for recurrent patients remain limited. Reimbursed second-line treatment options for renal cell carcinoma in Korea are Pfizer's Sutene, GSK's Votrient( pazopanib), and Inlyta. Cabometyx has demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) over Novartis’ Afinitor (everolimus) in recurrent renal cell carcinoma patients, but is non-reimbursed in Korea. In the METEOR trial, Cabometyx demonstrated a median PFS of 7.4 months, OS of 21.4 months, and ORR of 24%, making it the only second-line treatment option in renal cell carcinoma that showed efficacy in all three measures. However, its use is further limited due to its indication in addition to its non-reimbursement. The drug is approved in Korea as a monotherapy for patients with advanced renal cell carcinoma who have been previously treated with VEGF (vascular endothelial growth factor) targeted therapy. In-Keun Park, Professor of Oncology at Seoul Asan Medical Center Moreover, Cabometyx is not indicated for use in patients who developed resistance to first-line standard-of-care immuno-oncology combination treatment, because a VEGF inhibitor has not been used in the previous line of treatment. Professor Park explained, “Studies have confirmed the efficacy of Cabometyx over other second-line treatments, and has shown better results compared to Sutene as a first-line treatment in intermediate- and high-risk renal cell carcinoma.” He added, “When we look at the data from recent real-world studies and smaller studies where patients were administered Cabometyx after immuno-oncology treatment, the results are not bad. We're seeing response rates from 30%, up to 50%. However, its limited indication has made it difficult to use Cabometyx as second-line therapy.” The treatment paradigm is shifting...expert and international practice guidelines should be reflected#EB Professor Park emphasized that as international guidelines for renal cell carcinoma have changed, these latest treatment trends should also be reflected in Korea as well. International guidelines, including the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), and the European Association of Urology (EAU) recommend Cabometyx as the first-line treatment for renal cell carcinoma after use of immuno-oncology drugs in the first-line. However, in Korea, it is difficult to prescribe Cabometyx in the second line due to its limited indications and reimbursement conditions. Professor Park said, “I understand that the government needs to closely review the effectiveness of drugs based on clinical results. However, in line with the changing environment for first-line treatment of renal cell carcinoma, the insurance standards for later lines of treatment should reflect the opinions of experts related to pharmacological mechanisms and international guidelines. This is because many limitations remain to reconduct clinical trials and change the indication.” In other countries like Japan, Japan allows reimbursement for a single cancer type, regardless of the stage of treatment. In the United States, therapies are allowed to be used off-label if there is evidence to support it. As such, Professor Park explained that the treatment paradigm for renal cell carcinoma has changed internationally, but is not being reflected in Korea and goes against the constantly changing treatment trends with the excuse that it lacks clinical results. "We should aim for evidence-based medicine, but in the end, I would like the government to be more considerate of what is the optimal treatment for the people. In the process, treatment standards should be based on expert opinions and international guidelines.”
- InterView
- Targeted cardiomyopathy drug, Camzyos effective in Asians
- by Son, Hyung-Min Dec 19, 2023 11:19am
- Milind Y. Desai, a professor of Department of Cardiovascular Medicine at Cleveland Clinic, US The first targeted treatment option for obstructive hypertrophic cardiomyopathy has finally emerged. Obstructive hypertrophic cardiomyopathy (oHCM) is a sub-classification of hypertrophic cardiomyopathy that is characterized by LV outflow tract (LVOT) obstruction impeding blood flow from the heart to the rest of the body. Previously, the treatment options for HCM were limited to chronic disease treatments such as beta-blockers and calcium channel blockers. While these drugs could indirectly manage HCM symptoms, if there was no improvement, there were no other treatment options besides surgery. In this context, BMS’s development of Camzyos offered a targeted therapy option for HCM. Camzyos differs from existing drugs as it directly inhibits myosin, leading to improvements in symptoms and exercise capacity in patients. Camzyos functions by reducing the number of actin-myosin cross-bridges that constricts cardiac muscle, thus relaxing the cardiac muscle. In clinical trials, once-daily administered Camzyos showed significant improvement, bringing about half of the patients to asymptomatic levels. Additionally, 74% of patients experienced considerable improvement in obstructed left ventricular outflow, to the point where they no longer required consideration for Septal Reduction Therapy (SRT). Based on such clinical results, Camzyos was approved in May in Korea, becoming the first drug in Asia to be approved to enhance exercise capacity and alleviate symptoms in adult patients with symptomatic oHCM. Milind Y. Desai, a professor of Department of Cardiovascular Medicine at Cleveland Clinic in the US, analyzed that the demand for Camzyos will rise in medical settings based on results of the studies on Asian patients, as they have shown results consistent to those observed in global clinical studies. Q. What is the current global prevalence of HCM? The estimated global prevalence of HCM is about 1 in 500 or 1 in 200 people. Considering these figures, millions of people worldwide should be diagnosed with HCM; however, approximately 85% of these cases go undetected due to misdiagnosis, underdiagnosis, or delayed diagnosis. Based on a prevalence rate of 1 in 500, in the US with a population of approximately 340 million, it's estimated that there should be about 700,000 people diagnosed with HCM. However, the current number of diagnosed patients is estimated to be only about 100,000 to 120,000. This suggests a substantial disparity between the actual prevalence of the condition and the number of diagnosed cases. Q. What is the treatment strategy for HCM? Until recently, the treatment strategy for HCM primarily concentrated on alleviating symptoms. With no medications specifically approved for HCM, drugs for coronary artery disease, such as beta-blockers, calcium channel blockers, and disopyramide, were used for treating HCM. If symptoms failed to improve with these medications, patients had only invasive treatments, such as surgery, as alternatives. Unlike any existing treatments, Camzyos is the first therapy to directly target the underlying pathophysiology of HCM. Camzyos can inhibit excessive actin-myosin cross-bridges in cardiac muscle. By allowing only the necessary amount of actin-myosin binding to occur, it normalizes the excessive cardiac contractions, effectively treating the obstructed cardiac structure and its related symptoms. Q. In clinical trials, symptoms and exercise capacity of the patients who received Camzyos were significantly improved. In the EXPLORER-HCM trial, patients who received Camzyos achieved both primary and secondary endpoints with significant improvements over those who received placebo. A higher percentage of Camzyos-treated patients achieved each of the composite functional end point (an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (VO2) accompanied by an improvement from baseline of at least one NYHA functional class, an improvement from baseline of 3.0 mL/kg/min or greater in peak VO2 maintaining NYHA functional class) compared with the placebo group. Patients treated with Camzyos showed a higher proportion of relieved LVOT pressure gradients towards normal levels and enhanced quality of life compared to the placebo group. Overall, Camzyos showed significant improvements across all evaluated parameters when compared to the placebo, thereby confirming its superiority in terms of both safety and efficacy. In addition to sustained effectiveness observed in clinical trials, patients treated with Camzyos showed reduced hypertrophied cardiac muscle thickness and size to optimal levels and were resolved of issues with stiff cardiac muscles. Furthermore, in a separate clinical study, EXPLORER-CN which had been conducted in Chinese patients, the results were consistent with those observed in global studies, despite the fact that these patients started treatment at lower doses, confirming Camzyos is an effective treatment option for Asian patients. Q. If you have experience prescribing Camzyos, what actual treatment outcomes have observed with its use? How has it impacted patients’ prognosis and satisfaction with the treatment? Currently, approximately 7,000 patients across the US are receiving treatment with Camzyos. The real-world data indicates a discontinuation rate of Camzyos therapy at around 2.2%, which is lower than what was reported in clinical trials. Among the patients receiving Camzyos treatment at the Cleveland Clinic, there were no cases requiring myectomy, and even patients who had previously undergone myectomy at other medical institutions without symptom improvement have shown a positive prognosis after starting Camzyos treatment at the Cleveland Clinic. Q. In August, the European Society of Cardiology (ESC) updated its HCM guideline. What are the most noteworthy changes? In the past, HCM guidelines had to rely on limited evidence, such as small-scale observational data from individual institutions, retrospective analysis, or consensus opinions from experts. For the past nine years since 2014, there were no drugs that has produced enough data to justify updating the guidelines. During this period, no drugs have received a recommendation with a level of evidence higher than B. However, Camzyos has completely changed the circumstances. With significant efficacy demonstrated in two large-scale Phase 3 randomized controlled trials (RCT), Camzyos has received a recommendation of A based on the newly revised ESC guidelines, making it the first treatment option to receive the highest level of evidence. Nevertheless, there was some surprise and disappointment as Camzyos had hoped to receive a Class 1 recommendation but was instead granted a Class 2A recommendation. Currently, the American College of Cardiology (ACC) and the American Heart Association (AHA) are also preparing for guideline updates, with new announcements expected early next year. Q. In conclusion, how do you predict the paradigm of the HCM treatment will shift in the future? The first step would be assessing the patients diagnosed with HCM for the presence of symptoms. If symptoms are present, treatment could begin with first-line treatment options such as beta-blockers, calcium channel blockers, or disopyramide. If initial drugs fail to alleviate symptoms in HCM patients, it may be more effective to consider transitioning to Camzyos at an appropriate time, rather than simply increasing the dosage and continuing the treatment. However, it's important to know that treating HCM isn't a linear progression from beta-blockers to Camzyos, and then to surgery. Treatment should be tailored to the patient's specific condition, which might necessitate moving back and forth between these stages. The precision medicine approach is already applied in the field of HCM, with AI-based diagnostic tools identifying more patients, and therapies targeting specific genetic mutations are under exploration. Considering these advancements, the future of HCM treatment is expected to become more diverse, offering therapeutic options that are more appropriately tailored to each patient's circumstances.
- InterView
- ‘Leclaza can occupy 50% of mkt if used as combination'
- by Jung, Sae-Im Jul 28, 2023 05:30am
- Yuhan Corp’s Leclaza (lazertinib) was the first homegrown new drug to be approved as a first-line treatment for EGFR mutation-positive non-small-cell lung cancer. The industry’s eyes are now on how the drug will fare in the global market. Will Leclaza be able to rise as a new contender to AstraZeneca’s ‘Tagrisso (osimertinib)’ that is dominating the global market? The key lies in the clinical results of 'MARIPOSA', which is being conducted by Janssen. The Phase III MARIPOSA study directly targets the current first-line standard-of-care Tagrisso with Janssen’s ‘Rybrevant (amivantamab)’ and Leclaza combination. If the Rybrevant+Leclaza combination demonstrates a progression-free survival (PFS) superior to that of Tagrisso, this could bring major change to the current treatment environment. The interim results of MARIPOSA phase 3 are expected to be presented at the European Society for Oncology (ESMO) Congress 2023 which will be held in October. “If the MARIPOSA trial ends a success, third-generation options for the first-line treatment of EGFR-mutation-positive NSCLC will increase to 3 (Tagrisso, Rybrevant+Leclaza, Leclaza). I think it's very significant that two-thirds of the options include the use of Leclaza." Professor Byoung-Chul Cho (Medical Oncology, Yonsei Cancer Center) and Professor Ki Hyeong Lee (Hemato-Oncology, Chungbuk National University Hospital) Professor Byoung-Chul Cho (Medical Oncology, Yonsei Cancer Center) and Professor Ki Hyeong Lee (Hemato-Oncology, Chungbuk National University Hospital) met with the reporter at the LASER Symposium that was held on the 22nd for medical oncologists and relayed their anticipation on Leclaza’s potential as a global new drug. According to clinicaltrials.gov, a registry and results database of clinical studies, the MARIPOSA study divided 1,074 patients around the world into three treatment arms. Treatment Arm A will receive Rybrevant+Leclaza and Arm B and C will each receive Tagrisso and Leclaza as monotherapy. The study seeks to demonstrate that the Rybrevant+Leclaza combination therapy is superior to Tagrisso. Tagrisso has settled as the global standard of care with progression-free survival (PFS) of 19 months when used in the first-line. Therefore, achieving a statistically significant superiority will be very difficult. Conversely, if the clinical trial produces good results, it would also be that much of a game-changer. Professor Cho said, “The standard for statistical significance was set quite high in the clinical trial that compared Rybrevant+Leclaza and Tagrisso. I have high expectations for the study because I believe the cancer treatment paradigm will shift from the use of monotherapy to combination therapies. After the results of the MARIPOS clinical trial are presented, the company will sequentially start its approval process in the US. If approved, two of the three options in the field will include the use of Leclaza, and simple arithmetic can tell us that the drug can occupy up to 70% of the market share. "This will have a significant impact on prescriptions," he predicted. Although it is not the main point of the trial, the study may also serve as an opportunity to recognize the effect of Leclaza once again as it also evaluates Leclaza and Tagrisso as monotherapy in one trial. Leclaza demonstrated a long progression-free survival of 20.6 months in the global Phase III LASER301 trial that was presented last year. Although this is longer than what Tagrisso had achieved in its Phase III trial, the two are not directly comparable due to the different patient groups enrolled in each study. The MARIPOSA study includes Tagrisso and Leclaza monotherapy arms, which allows for the efficacy between the two to be examined. Professor Lee said, “I want to know if the results from the LASER301 clinical trial and its subgroup analysis will show consistently in the MARIPOSA study. If we see positive results in that trial, it would be an opportunity for HCPs to recognize the efficacy of Leclaza. If successful, I believe Leclaza would be able to take over 50% of the market.” Tagrisso is also seeking to expand its indication through the FLAURA2 trial, which examined Tagrisso’s use in combination with chemotherapy. The combination obtained statistically significant top-line results recently and will announce the results in the second half of the year. However, the professors believe the FLAURA2 trial will not cause a major change in the current treatment landscape. Professor Cho held the 1st generation gefitinib+chemotherapy combination in the past as an example. The combination had shown a significant improvement in overall survival (OS), and a related paper was published in the Journal of Clinical Oncology (JCO) published by the American Society of Clinical Oncology (ASCO) and also listed in international guidelines. However, no one has been actually prescribing this combination on-site. Cho added, “Those who have experience dealing with a lot of EGFR mutations are confident that they can achieve the same results with monotherapy without adding chemotherapy. Adding chemotherapy is effective with immunotherapy, but the situation is different in EGFR-mutation-positive NSCLC, as we are already achieving high response rates with targeted therapies alone. The MARIPOSA trial is at another level compared with the FLAURA2 trial.” Professor Lee said, “Chemotherapy not only brings side effects, but I'm just personally not sure if it works. I think chemotherapy will disappear from the market in the future. With the advent of targeted therapy, there is no reason for us to go back and use chemotherapy, so it is difficult to understand why we should consider using it again even as a combination.”
- InterView
- Immunotherapy for early lung cancer was used
- by Jun 29, 2023 05:56am
- As immuno-anticancer drugs can be used in early lung cancer, the prognosis of patients is improving. Unlike before, when chemotherapy and concurrent chemoradiation were all, it is evaluated that the number of cases of 'complete pathological remission' has increased. Opdivo was approved by the Ministry of Food and Drug Safety in October of last year for adjuvant therapy before non-small cell lung cancer surgery. This is the first case in which immuno-oncology drugs have advanced into adjuvant therapy before surgery. Specifically, Opdivo can be used along with chemotherapy in non-small cell lung cancer patients with tumors larger than 4 cm or with positive lymph nodes. The treatment proceeds by using 3 cycles of Opdivo + chemotherapy and undergoing surgery. Prof. Lee Kun-guk (left), Prof. Ahn Byeong-cheol (right), National Cancer Center Lee Kun-Guk, a professor of pathology at the National Cancer Center, gave a positive evaluation, saying, "The introduction of immuno-anticancer drugs has greatly increased the number of cases of pathological CR, which were rarely seen before." "CR was observed in 5 out of 7 cases at our hospital. Through a conversation with Professor Lee and Professor Ahn Byeong-Cheol of the Department of Hematology and Oncology at the National Cancer Center, Daily Pharm examined the changes brought about by the advent of immuno-anticancer drugs in adjuvant therapy before lung cancer surgery. -We know that the way to expect a complete cure for early lung cancer is through surgical treatment. What is the percentage of patients who can undergo surgery by stage? There are cases of recurrence even after surgery. What if there has been an unmet need? =Professor Ahn Byeong-Cheol (referred to as Professor Ahn): Looking at each stage, 80% of stage 1, 60% of stage 2, and 50% of stage 3A can be operated. It is known that all stages 1 to 3A can be operated, but not all patients can operate because of the complex effects of various factors, such as the patient's psychological burden for surgery and the state of the disease, in addition to the stage. Lung cancer is a carcinoma with a high recurrence rate, with studies showing that even stage 1 patients recur up to 40%. Three out of four patients with stage 3 disease with a high stage show recurrence. Therefore, there has always been an unmet need for therapies that can reduce the recurrence rate and improve the prognosis. There have been many attempts to increase the success rate of surgery by reducing the size of the tumor as an adjuvant therapy before surgery for patients with a difficult surgery. However, chemotherapy, which was a representative preoperative adjuvant therapy, did not show a therapeutic effect to such an extent that the pathological CR ratio remained in the single digits. Simultaneous chemoradiation had limitations due to toxicity and side effects such as pneumonia, decreased lung function, and adhesions. -Recently, immuno-anticancer drugs appeared in adjuvant therapy before lung cancer surgery in combination with chemotherapy. I am curious to see how much treatment has been achieved with the experience of actually prescribing this therapy. =Professor Lee Kun-Guk (Professor Lee): So far, immunotherapy was used as an adjuvant therapy before surgery in 7 cases, and in 5 of them, so-called pathological CR, in which lung cancer was not found, although lumps remained, could be confirmed. Certainly, it shows a significantly improved treatment effect compared to previous preoperative adjuvant therapy. Previously, pathological CR was rarely reached. Therefore, it was difficult to evaluate the treatment effect. If complete pathological remission is frequently achieved, as in the combination of Opdivo and chemotherapy, a significant part of the worry can be relieved from the perspective of medical staff. If it is confirmed that there is no cancer mass when observed under a microscope, a lot of burdens is relieved for pathologists who have to quantify the treatment effect. -Are there any concerns about missing the right time for surgery when treated with adjuvant therapy before surgery? =Professor Ahn: I think it is homework to be solved in the preoperative adjuvant treatment. Statistically, less than 10% of patients who were able to undergo surgery may miss the timing due to adjuvant therapy before surgery and may not be able to undergo surgery. However, the ratio of patients who underwent surgery in clinical trials with this immunotherapy was 83.2%, higher than 75.4% of the chemotherapy alone group. Ultimately, I think it is important for medical staff to select and treat patients who are suitable for preoperative adjuvant therapy. -Opdivo + chemotherapy combination therapy has been approved for use regardless of the PD-L1 expression rate and major gene mutations. Is there any difference in actual effect? =Professor Ahn: The higher the PD-L1 expression rate, the higher the therapeutic effect of immuno-anticancer drugs. The higher the PD-L1 expression rate, the lower the risk of recurrence and the higher the pathological complete response rate. However, since it showed a significant improvement effect in all patient groups regardless of the PD-L1 expression rate, it is prescribed regardless of the actual clinical setting. =Professor Lee: In patients with target gene mutations, the effect of immuno-anticancer drugs is relatively low, and a follow-up study on this is likely to be necessary. However, I think it is meaningful in that the opportunity for adjuvant therapy before immuno-oncology surgery is open to all patients. -It is expected that the importance of pathological examination will be further emphasized in lung cancer treatment. What do you think the pathological diagnosis system needs to change in the future? =Professor Lee: I think the pathology examination fee needs to be improved. About 400 genes are identified by the NGS test at medical institutions, and the fee is 1.5 million won based on the main hospital, which is a secondary hospital. This is a very small amount compared to about 6 million won in the United States. In Korea, the number of genes required to be tested is low compared to the number of genes that need to be tested, making it difficult for NGS testing to be universalized. Personally, I think NGS testing will become more common in more hospitals if NGS testing is lightweight and appropriately priced so that only necessary genes are tested rather than testing all 400 genes.
- InterView
- The use of HTN combi tx in Korea is the highest in the world
- by May 23, 2023 05:53am
- Park Chang-kyu, Chairman of the Society of Hypertension (Korea University Guro Hospital) (photo by Dailypharm) Korea is the best in the world for complex drugs related to hypertension and hyperlipidemia. The drugs prescribed for each patient’s condition will change, but recently there is a growing trend to use complex drugs that are convenient to take.” Park Chang-gyu, chairman of the Society for Hypertension (Professor, Cardiovascular Center, Korea University Guro Hospital, 64), met with Dailypharm at the '2023 Korean Society of Hypertension Spring Conference' held at Exco in Daegu on the 20th and said this. Park Chang-gyu, president of the Society, graduated from Korea University College of Medicine and received a master's degree from the graduate school. He received a doctorate in internal medicine from Korea University School of Medicine. He was an exchange professor at the University of Ottawa, Canada. Since 2014, he has been the head of the cardiovascular center, the head of internal medicine, and the chairman of the faculty council at Korea University Guro Hospital. Since last year, he has been serving as the president of the Hypertension Society. Hypertension is one of the chronic diseases that most require lifelong treatment. This disease can lead to a healthy life through management and treatment. If it is judged asymptomatic and not treated, it can lead to fatal complications. Essential hypertension occurs in 90% of hypertensive patients. It is a disease that is difficult to treat because the cause is unknown. Efforts to control blood pressure to normal should be made for the rest of pt's life. "The trend of prescribing high blood pressure drugs has changed to prescribing a combination drug rather than giving individual drugs such as ARB or CCB," said Park. "It has already been published in papers that the combination drug is beneficial for patient treatment," Park said. Park also presented his opinion on areas where pharmaceutical companies can secure competitiveness in the complex drug market where competition is overheated. “To strengthen the competitiveness of complex drugs, first of all, the scientific basis for the treatment effect or safety is the most important,” said Chairman Park. There will be," he said. Park also said, "Some companies can coat drugs well so that side effects such as gastrointestinal disorders do not appear, and some companies can develop improved formulations for drugs that are weak to moisture and can show reasonable drug prices by improving the production process." "Considering various factors such as technology and price competitiveness, we will be able to secure the competitiveness of high blood pressure combination drugs," he said. With an increasing number of young hypertensive patients, “We will engage in community education and exchanges with global societies” Park also introduced that the number of young hypertensive patients is increasing and that active management and treatment are needed, as well as strengthened treatment guidelines. According to HIRA's health care big data, hypertensive patients aged 20 to 29 increased from 29,123 in 2017 to 42,048 in 2021, a 44.4% increase. During the same period, the number of hypertensive patients aged 30 to 39 increased by 26.6% from 166,644 to 210,890. Park plans to further publicize the revised treatment guidelines in November last year for the increasing number of young hypertensive patients and health care at the age of 100 years old. The revised 2022 hypertension treatment guidelines recommended lowering the target blood pressure to 130. The target blood pressure was lower than the previous guideline. The Society of Hypertension also gave a recommendation grade for the appropriate use of combination drugs through an amendment. This means that it is recommended to consider treatment more actively than before. Park said, “Now, except for simple hypertension, most hypertension meets the enhanced blood pressure standard.” “It was announced in November 2022, but education that introduces the reason for lowering the standard and research needs to be known more starting this year.” "he said.
- InterView
- ‘Even a 0.2 vision is a miracle to some’
- by Eo, Yun-Ho May 15, 2023 05:41am
- Professor Suk Ho Byeon The reason for the slow development of new drugs in a specific disease can usually be attributed to one of the following two reasons. Low disease awareness or difficulty in developing the drug itself. The one-shot gene therapy Novatis’s ‘Luxturna (voretigene neparvovec)’ is a drug that overcame both barriers. Luxturna, which is a treatment for IRD (Inherited Retinal Dystrophy) caused by the mutation in both copies of the RPE65 gene, is the first treatment option developed for the difficult rare genetic condition. IRD is a rare intractable disease caused by a mutation in the gene responsible for the structure and function of retinal visual cells. It includes over 20 types of ophthalmologic conditions, and around 270 causal genes are known to be implicated in IRD. RPE65-IRD, caused by the mutation in both copies of the RPE65 gene, causes abnormalities in the visual cycle of the retina that converts visual information into a neural signal and delivers it to the brain. The mutation in the RPE65 gene reduces the RPE65 protein essential to the visual cycle and destroys the retinal cell, gradually narrowing the field of vision to eventually result in loss of vision. With only 6 patients found with IRD in Korea, patients with the condition reach legal blindness in their adolescence, at about 16 to 18 years of age, then progress to complete blindness. Due to the lack of a fundamental cure, only conservative treatment that could temporarily delay symptoms was available until now. WIth its release, Luxturna became the first drug introduced into the field that could prevent blindness. Dailypharm met with Professor Suk Ho Byeon, Department of Ophthalmology at Sinchon Severance Hospital to hear about the significance of RPE65-IRD and Luxturna. Professor Byeon had recently coauthored a consensus paper on RPE65-IRD published in the Korean Journal of Ophthalmology, an English journal published by the Korean Ophthalmological Society. -The consensus paper you released recently seems to have covered the whole content on RPE65 mutation-associated IRD starting from its concept. It felt more like a clinical practice guideline. Does the fact that this paper was published signify the lack of content on the diagnosis and management of RPE65-IRD in Korea? It can be said so. Due to the characteristics of the disease, treatment is rare in any form of IRD. Not many doctors have experience using drugs to treat the disease. So we tried to relay the existence of such a disease and the need to look for the disease. With the first drug released fRPE65-IRD, hope is rising among all IRD patients including those with genetic mutations other than the RPE65 mutation. However, since there was little information arranged on the disease itself as well as its diagnosis and treatment, we decided to bring together experts who had experienced or were familiar with the disease in Korea to arrange the information on the disease. The consensus paper includes information on what RPE65-IRD is, what kind of patients are considered to have IRD, its global epidemiology and epidemiology in Korea, to which extent genetic mutations are reported, and how and whom should receive gene tests for the disease. -As you’ve mentioned, the consensus paper includes content on finding the subjects that should receive genetic testing. Which parts should the doctor check during gene testing? One of the most prominent characteristics in these patients is that they had poor eyesight from an early age. This may be difficult to notice during infancy, but over time, the patient’s eyesight decreases significantly compared to normal people and is accompanied by night blindness. However, with so many areas bright at night, night blindness is sometimes discovered late these days. Patients with severe symptoms also experience eye tremors. However the features of the disease can vary even among patients affected with the same genetic mutation. Some patients show fewer symptoms and some do not have night blindness. Therefore, the disease is difficult to identify based solely on symptoms. Therefore, in pediatric patients, I think it is better to proceed and conduct a genetic test even if at the smallest suspicion. -So Luxturna was released in the field that had no available drugs. The drug received attention as the first gene therapy for ophthalmic diseases. What is your opinion on the value of the drug? That would be difficult for general ophthalmologists to judge. I can better explain its significance because I have experience treating patients with Luxturna. Patients with poor eyesight ever since childhood rarely visit the hospital, so doctors often do not know how these patients are faring. In that sense, it is difficult to estimate how much a patient's life would have improved with improved eyesight. Ophthalmologists measure both visual acuity and visual fields. This index of visual acuity and field of view measures how far off the patients’ eyesight is from those of normal people. Patients who were treated with Luxturna showed much improvement in the visual field and visual acuity. The improved visual acuity was about 0.2. For non-patients, visual acuity of 0.2 may feel like a poor condition, but for those that had almost no vision, even a 0.2 vision can be of great benefit. I was very surprised to see a patient I treated working part-time at a coffee shop. A patient who could go blind escaped the danger with Luxturna. In this sense, the effect of such treatment should not be judged based on standards set for normal eyes. - Luxturna received the non-reimbursement decision last month from the National Health Insurance Review and Assessment Service’s Drug Reimbursement Evaluation Committee. The committee pointed to how the condition is not life-threatening and is a high-priced drug as a barrier to reimbursement. There also seems to be a difference between the government and pharmaceutical companies regarding reimbursement standards. Reimbursement is a complex issue that requires broad and serious considerations. Since Luxturna is a gene replacement therapy, I know there have been disagreements on the remaining target cell and the criteria for recognizing its effect. As a doctor, I can definitely say that there can be no crystal-clear standard for evaluating living cells. Some cases can only be determined after treatment. Since it is such a rare condition, it is difficult to even estimate how many cases there will be.
- InterView
- Samsung Bio, investing in Swiss ADC bio company
- by Hwang, Jin-joon Apr 13, 2023 05:43am
- Panoramic view of Samsung Biologics. (Photo Samsung Biologics) Samsung Biologics announced on the 12th that it invested in Araris Biotech AG through the 'Samsung Life Science Fund' along with Samsung C&T. This investment was conducted exclusively by Samsung as a strategic investor (SI) prior to Araris Biotech AG's Series A phase. The investment is expected to be used for the further development of antibody-drug conjugate (ADC) candidates by Araris Biotech AG. ADC is a drug that combines a drug with an antibody and is one of the next-generation treatments. Araris Biotech AG is a company established in 2019 through the Federal Institute of Technology in Zurich, Switzerland. It has next-generation ADC linker technology. Araris Biotech AG's next-generation ADC linker technology has the advantage of attaching drugs to off-the-shelf antibodies without the need to redesign the antibody. This can reduce the time and cost required for drug development. Samsung plans to cooperate with Araris Biotech AG in the field of ADC treatment production and development. Previously, in July 2021, Samsung created a life science fund worth 150 billion won to discover new businesses in the biofield.
- InterView
- CDK4/6 latecomer Kisqali exudes confidence in its effect
- by Jung, Sae-Im Apr 11, 2023 06:11am
- Novartis’s Kisqali (rivociclib), a latecomer CDK4/6 inhibitor used in metastatic breast cancer, is taking on an unexplored path, away from other CDK4/6 inhibitors. The drug has demonstrated efficacy in aggressive forms of breast cancer, which had not been attempted by other CDK 4/6 inhibitors. Aggressive breast cancers appear relatively often in Korea where the proportion of younger aged patients is large, but the patients’ only available option was to use highly toxic chemotherapy. In a recent interview with Dailypharm, Seock-Ah Im, Professor of Hemato-Oncology at Seoul National University Hospital said, “Younger breast cancer patients have a higher probability of accompanying visceral metastasis because of their rapid cancer growth and aggressive clinical pattern. However, due to the clinical practice guidelines that recommended using chemotherapy for the past 20 to 30 years, there were doubts about whether to use CDK4/6 inhibitors. However, Kisqali's recent study convinced me of the viability of using CDK4/6 therapies." The recent study mentioned by Professor Im is the RIGHT Choice trial that was released in December last year. The trial studied aggressive hormone receptor–positive, HER2-negative advanced breast cancer patients that had symptomatic visceral metastasis, rapid disease progression or impending visceral compromise, or marked symptomatic nonvisceral disease. Although the CDK4/6 inhibitor+ endocrine therapy is currently used as the standard treatment for breast cancer in the first line, chemotherapy was still used in patients with rapid disease progression or visceral metastasis. Metastatic breast cancer often spreads to the lungs, liver, or brain, and when metastasis occurs, symptoms such as shortness of breath and pain may arise. In such cases, it is difficult to quickly reduce tumor size with hormone therapy alone. CDK4/6 inhibitors have been introduced as a new option in this field, but no data existed demonstrating their effectiveness in these patients. Kisqali is the only CDK4/6 inhibitor class drug to demonstrate an improved effect over combined chemotherapy in aggressive breast cancer. Results showed that the median progression-free survival (PFS) of the Kisqali + endocrine therapy combination was 24.0 months, a 1-year extension over the 12.4 months recorded by the control group (HR=0.54). The median time to treatment failure in the Kisqali combination group was 18.6 months, which was at least 10 months longer than that of the control group (HR=0.45). In terms of safety as well, the Kisqali combination group had a lower rate of treatment-related serious adverse reactions and treatment discontinuation rate compared to the combination chemotherapy group. Professor Lim said, "The scope of use of CDK4/6 inhibitors including Kisqali in HR+ breast cancer has increased significantly over the past two years. In line with the broadened scope of use of CDK4/6 inhibitors that changed the treatment paradigm of HR+ breast cancer, the ground is being laid to allow their more active use.” Professor Seock-Ah Im-I heard that Asian doctors first suggested the initiation of the RIGHT Choice trial = I am a member of a group of researchers that seek to improve the treatment of young breast cancer patients. As members, specialists from Asian countries, including Korea, Taiwan, Hong Kong, and Singapore, gather together to discuss and study how to improve the treatment environment for young breast cancer patients. During a meeting, the researchers suggested that a combination therapy that uses a CDK4/6 inhibitor could improve the quality of life and have a better antitumor effect than combination chemotherapy, and a research proposal was sent to pharmaceutical companies based on the suggestion. We proposed a study because young patients in their 40s and 50s occupy the majority population in Asia, compared to the West, which is dominated by elderly patients in their 60s and 70s. Breast cancer often takes on an aggressive form among young patients due to the fast cancer growth rate and relatively faster cell division. This means patients are highly likely to have accompanied liver or lung metastases. These doctors had been using chemotherapy as the first-line treatment for HR+ patients because it takes a long time to improve the patient’s symptoms by reducing cancer size with hormone treatment. Chemotherapy allows the tumor size to reduce within 1 to 2 months and the symptoms improve. However, it is also highly toxic. Therefore, a consensus was reached on how combining hormone therapy and targeted therapy instead of chemotherapy, which is difficult to be approved, would yield better results. Novarits’s Kisqalit team accepted the request, and so the RIGHT Choice study was conducted to demonstrate the actual improvement effect.. -How would you interpret the RIGHT Choice trial results? s= There had been clinical trials comparing hormone therapy and CDK4/6 inhibitors with oral anticancer drugs. However, this study is the first to show improvement compared to a combination therapy that is administered in two injections of cytotoxic anticancer drugs. In general, if a patient starts anticancer therapy, the tumor size is first reduced and then starts to grow again. The time until disease progression, that is, the time to symptom relief after chemotherapy and relapse is about 5 to 6 months. In clinical practice, the median time to treatment failure in the Kisqali combination group was 18.6 months, about twice as large as 8.5 months in the control group. Median progression-free survival was also extended by about 1 year compared to the control group. In particular, this study brings more significance because it includes premenopausal women and proves that a more comfortable initial treatment can be performed in premenopausal patients with more aggressive liver cancers or those with lung metastases. The limitation is that the study enrolled patients whose control group could be either one of two cytotoxic anticancer drugs and have a normal range of liver function and daily performance ability to some extent. The study did not include patients whose daily performance is so poor that they are almost bedridden. There are some cases we feel it’s inappropriate to conduct chemotherapy in some patients with visceral metastasis. However, on the other hand, there were many questions about whether it was really okay to use CDK4/6 inhibitor combination therapies. The study convinced me of the potential held by 'CDK4/6 therapy.’ -Kisqality was the last of the three CDK4/6 inhibitors to be introduced to the market. However, if you look at the recent sales records reported by the market research institution IQVIA, Kisqali made notable sales. How reliable are new drugs like Kisqali? =The data was interesting. Having participated in the trial of all three CDK4/6 inhibitors, Ibrance, Verzenio, and Kisqali, I am well aware of the benefits and disadvantages of each drug. Therefore, doctors tend to select drugs after comprehensively considering each patient’s safety, the patient's environment, and condition. In the case of postmenopausal women, side effects such as age, presence or absence of pulmonary embolism or venous thrombosis, and probability of pneumonia are considered. In addition, bone marrow function, liver function, electrocardiogram abnormality, and diarrhea are also considered. However, re-menopausal breast cancer patients didn't have as many options to choose from. Before Ibrance, the patient had to first remove both ovaries to use Ibrance. Fortunately, the combination therapy with Ibrance after ovariectomy did not require chemotherapy, and had only a few side effects other than a slight decrease in white blood cell count, so this method was mainly used. Later, the MONALEESA-7 study played a significant role.in allowing premenopausal women to use Kisqali combination therapy without ovarian resection.
- InterView
- The rebate effect is not just employee deviation
- by Kim JiEun Mar 22, 2023 05:47am
- The pharmaceutical company, which was suspended from sales due to the confirmation of the salesperson's suspicion of providing rebates, argued that there was no reason for the disposition, saying that it was only an employee's deviance, but the court did not accept it. The Suwon District Court recently dismissed a request for cancellation of a disposition to suspend sales of pharmaceuticals filed by a pharmaceutical company against the Gyeongin Food and Drug Administration. The reason for the disposition of pharmaceutical company A is as follows. Mr. B, who was a salesperson at this company, provided a total of 41 million won worth of economic benefits to the hospital administration manager several times from October 2013 to January 2016. As the charges were confirmed, Mr. B received a summary order of a fine of 10 million won for violating the Pharmaceutical Affairs Act around February 2017. The Gyeongin Food and Drug Administration issued a three-month suspension of drug sales to Pharmaceutical Company A in October 2021, four years after going through the prior notification procedure. The reason for the disposition was in accordance with Mr. B's summary order. Regarding this disposition, Pharmaceutical Company A argued that there was no reason for the disposition and that the KFDA's disposition violated and abused its discretion. First of all, the pharmaceutical company said the reason why there is no reason for disposition, "(Rebate) is only Mr. B's personal deviation, and the company has never been involved." "There is a legitimate reason for not being a person who provided economic benefits, or for not being able to blame for the neglect of duty." “It was difficult for the company to know Mr. B’s rebate act, and it was only after four years had elapsed since the summary order, in this case, was finalized,” he said. Considering that the education was conducted and Mr. B's act was an aberrant act, this disposition violates the principle of proportionality and responsibility, and is illegal as it deviates from and abuses discretion.” However, the court completely refuted the claim of pharmaceutical company A. First of all, it was emphasized that Mr. B's kickback behavior was not regarded as Mr. B's individual act and that the company was also responsible for it. The court said, “Mr. B, who was an employee of a pharmaceutical company A, committed an act in this case in which he provided economic benefits to medical personnel, etc. in the process of carrying out sales duties entrusted by the company.” is ultimately vested in the company. The responsibility for the violation of administrative obligations that occurred in the process is also acknowledged as partly attributable to the company.” The pharmaceutical company said that it did not fulfill its obligations even if it provided education related to fair trade self-compliance to its employees. While pointing out that the 3-month suspension of business was not excessive as the company claims, the court also effectively reviewed the precedent in which the company was previously suspended for 3 months due to illegal kickbacks. The court said, "It is acknowledged that the company conducted regular CP (Compliance Program) training for its salespersons, but the contents of the training only seem to be of a general level." It is difficult to admit a legitimate reason that cannot be blamed for neglect of duty based on circumstances alone.” The court continued, “Although all of the 35 million won in cash that Mr. B provided to the hospital administration manager does not appear to be a rebate to promote the drug sales of this pharmaceutical company, considering the purpose of the case that the standard, in this case, did not determine the degree of disposition in proportion to the amount of the rebate. If so, it is difficult to conclude that the disposition, in this case, is unfair.” Company A’s claim is dismissed without reason.”
