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- 2026-06-24 22:53:17
- Policy
- MFDS to resolve production of chemotherapy drug '5-FU'
- by Lee, Hye-Kyung Jan 10, 2024 05:42am
- MFDS resolves One of the domestic pharmaceutical companies has agreed to produce the chemotherapy drug ‘5-fluorouracil (5-FU) injection.’ This measure will significantly aid in the treatment of cancer patients. ‘Since November last year, we received an information from the Korean Society of Health-system Pharmacists about a drug shortage of the chemotherapy drug 5-FU, and we reached out to the manufacturing company to investigate the cause,’ Kim Seonyoung, an official from the Ministry of Food and Drug Safety (MFDS)’s Heath Insurance Policy Review Committee stated. JW Pharmaceutical is responsible for the distribution of 5-FU, with Il Dong pharmaceutical serving as the Contract Manufacturing Organization (CMO). The MFDS discovered that Il Dong Pharmaceutical's efforts to upgrade certain facility units disrupted the production schedule of 5-FU. “To facilitate the drug’s distribution, we have expedited the production schedule, including stages like product quality testing and post-manufacturing processes. We have confirmed successful distribution of the drug on January 4th,” Official Kim stated Furthermore, another domestic pharmaceutical company has agreed to starting production of 5-FU as soon as the active ingredient is secured. This is expected to significantly improve the efficiency of the drug’s distribution starting from next month. Only one domestic pharmaceutical company is currently responsible for the distribution of 5-FU. To prevent any potential distribution instabilities, the committee inquired with several domestic pharmaceutical companies about their ability to produce the drug,” Official Kim mentioned. “With one of these companies now committed to distribution, more efficient distribution is likely starting in February.” The domestic pharmaceutical company that has agreed to produce 5-FU has requested not to disclose its name publicly. The Korean Pharmacists for Democratic Society (KPDS) announced a statement in response to the news about the supply shortage of 5-FU, a drug that has been listed as a shortage prevention drug (SPD) since 2010, that began in Dec. 2023. “Cancer patients are facing delays in chemotherapy schedules by 1 to 4 weeks or are frequently switching to alternative drugs,” the KPDS criticized. “The government claims to have a system in place for monitoring the supply and demand of essential medicines and receiving company reports on supply halts, in collaboration with relevant agencies and experts. However, details regarding the government's actions and corrective measures are lacking.”
- Product
- Saxenda’s shortage prolonged…raises inconveniences
- by Kang, Hye-Kyung Jan 10, 2024 05:42am
- Saxenda's prolonged out-of-stock status is inconveniencing consumers as well as pharmacies. As many patients set New Year’s resolutions of losing weight at the beginning of the year, the lack of Saxenda is causing dissatisfaction among pharmacies and consumers. Even diabetes patients are experiencing the inconvenience of insulin stockouts, including Saxenda. According to a local pharmacy, Saxenda’s stock shortage began to surface around November last year. Since then, supply and demand disruptions spread across the country, and it is now commonplace for patients to leave empty-handed from. pharmacies, even with prescriptions. Pharmacist A said, " Although many people are deciding to lose weight with the start of the new year, they can't fill their prescriptions because the pharmacies do not have the medicine. Many of those who come in with prescriptions complain that they have already visited several pharmacies due to Saxenda’s stock shortage.” While some doctors have reportedly notified the patients of this stock shortage and are not issuing prescriptions, many doctors who prescribe outpatient prescriptions do not give prior notice, leaving patients to do all the legwork. Pharmacist B said, "I've only heard that the manufacturer is experiencing difficulties in meeting the supply and that the supply will resume later this month, but I don’t know if this is accurate information. Most pharmacies will have also run out of stock due to the prolonged shortage.” Due to its rarity, local communities and diabetes communities are filled with posts asking which pharmacies still have remaining stock of Saxenda. This has led to some illegal trading between individuals or marketing by clinics. Because second-hand platforms forbid drug transactions between individuals, this has led to illegal transactions through open chat rooms. Dailypharm also covered the issue of second-hand trading of self-injectable drugs in open chat rooms in October last year. Pharmacist C said, “There are also posts that promote their clinics using the desperate psychology of consumers in finding Saxenda in stock. Although these advertisers use different nicknames for each internal cafe, the content is the same. I suspect these are PR posts uploaded by part-timers. It doesn't seem right that some clinics are using the stock shortage to promote their clinics when pharmacies are out of stock of Saxenda and unable to dispense the drug. Meanwhile, the Korean Pharmacists Association for a Healthy Society urged the government to take a responsible stance and address the out-of-stock drugs. "The severity of the problem is illustrated by dozens of posts on cancer cafes by cancer patients saying that they were unable to receive necessary treatment due to stock shortage, and the piling comments and inquiries on which hospitals have the necessary drugs. The government should take the best measures to ensure that citizens have the belief that the drugs they take today will be available tomorrow. We look forward to the government's efforts in ensuring the public to use essential medicines without worries."
- 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.
- Opinion
- [Reporter’s View] Be generous and provide tangible benefits
- by Eo, Yun-Ho Jan 10, 2024 05:42am
- Expectations of pharmaceutical companies that own new drugs have been rising in the light of the new year. The reason for this is the ‘Plan for Appropriate Compensation of the Innovative Value of New Drugs' that the government announced at the end of last year. According to the announcement, the government will grant reimbursement for innovative new drugs that have recognized innovativeness even if their economic feasibility exceeds that of the ICER threshold, an economic evaluation indicator. The criteria for innovativeness are those that satisfy all of the following conditions: a drug ▲ with no substitute or therapeutically equivalent product or treatment ▲ that demonstrated clinically meaningful improvement, such as a significant extension in survival, and ▲ has been approved by the Ministry of Food and Drug Safety through GIFT or received a breakthrough therapy designation (BTD) by the US FDA or a priority review (PRIME) by the European Union’s EMA. All three conditions must be met to qualify as an innovative drug. Although there is no documented figure, it is generally accepted that the ICER threshold for insurance reimbursement is KRW 50 million in Korea. Even drugs whose ICER value is KRW 50 million are rarely listed. In other words, the government announced that it will apply a flexible ICER threshold for drugs designated as an innovative new drug and satisfy all the conditions above, allowing such drugs an easy pass across the economic evaluation hurdle. This flexible application of the ICER threshold has been the industry’s greatest desire for some time. But there are also concerns over the large disappointment the high expectations may bring. If the actual increase in the threshold is less than expected, the pharmacoeconomic evaluations will still be a serious hurdle. If the KRW 50 million threshold, which was rarely applied, just becomes the norm, or the threshold is only increased by around KRW 5 million to KRW 10 million, their actual benefit will be minimal. This is not for all drugs, but just the innovative new drugs that meet all of the three conditions above. In fact, even if the threshold is raised by KRW 20 to KRW 30 million, the pharmaceutical industry may still long for a larger benefit. This will be especially true for drugs that have shown too much clinical improvement compared to existing drugs to demonstrate cost-effectiveness, i.e., drugs that are likely to be designated an innovative new drug. And these drugs will only increase in the future. As the government has already expressed its willingness to provide benefits, it would have devised a practical system to implement this year. All this reporter would like to ask of is, to be generous when giving out benefits. We know that the government is devising measures to cut costs along with measures that provide preferential treatment, therefore, all we ask is for the government to provide clear and generous benefits in areas it already decided to do so.
- Policy
- Will Enhertu be discussed in this year’s 1st DREC meeting?
- by Lee, Tak-Sun Jan 10, 2024 05:42am
- The schedule for the Health Insurance Review and Assessment Service’s Drug Reimbursement Evaluation Committee meetings in 2024 has been finalized and released. The committee meeting will be held at the beginning of each month, starting with the first meeting on the 11th of this month. According to industry sources on the 8th, the 2024 DREC meeting schedule has been finalized. It will be held at the start of each month - on the 11th of this month, the 1st of next month, the 7th of March, the 4th of April, and the 2nd of May. At this month's meeting, it will be interesting to see if the new breast cancer drug Enhertu, which has been struggling at the pharmacoeconomic evaluation stage, will be presented for deliberation. Although the drug offers a significantly improved effect over existing drugs, it has faced difficulties in pharmacoeconomic evaluations due to its prolonged administration period. Therefore, when the government recently announced that the ICER threshold will be flexibly operated for innovative new drugs in the 'Innovative New Drug Appropriate Value Recognition Plan', Enhertu was considered to become a beneficiary. However, the plan to recognize the fair value of innovative new drugs has not yet been implemented. If Enhertu’s reimbursement agenda successfully passes the DREC review, it will not have to wait for the new system to settle into the country. Last month, Enhertu reportedly submitted supplementary pharmacoeconomic evaluation data to HIRA. In addition, an application for a price increase adjustment for the pediatric cough expectorant tulobuterol will be reviewed by the committee. Tulobuterol is facing difficulties in supply and demand due to the discontinuation of the original product, the increase in the unit cost of raw materials, and the increase in pediatric respiratory diseases. In response, the government plans to increase the drug price to encourage production. 2024 DREC Meeting Schedule The 2024 reimbursement adequacy reevaluation plan is also expected to be discussed in the February meeting. The first results of the reevaluation are expected to be presented to DREC in its August meeting and the final results at the December meeting. In addition, the reevaluation of sodium hyaluronate eye drops, which was not decided last year, is also expected to be redeliberated and reported to the DREC within the year. In addition, it is analyzed that the reevaluation of drug prices through external reference pricing, and the pharmacoeconomic evaluation data waiver system among others, may be discussed at this year's meeting.
- Company
- K-pharma advances in new Alzheimer’s drug discovery
- by Jan 09, 2024 05:50am
- New drugs for treating Alzheimer’s disease developed by Korean pharmaceutical companies have entered the late phase of clinical trials, and industry watchers are closely monitoring their potential for commercialization. Aribio has recently submitted an Investigational New Drug (IND) application for its oral treatment candidate AR1001 for Alzheimer’s disease, to eight European countries. Aribio is about to enter the late phase of clinical trials in Europe, following its success in initiating Phase 3 clinical trials in Korea and United States. Additionally, each of the new Alzheimer’s disease drug candidates developed by GemVex, CHA Biotech, and NKMAX has entered Phase 2 clinical trials. The Korean pharmaceutical companies including Aribio (candidate product: AR1001), GemVex (candidate product: GV1001), CHA Biotech (candidate product: CB-AC-02), NKMAX (candidate product: SNK01), Shaperon (candidate product: Nucerin), and Neurorive (candidate product: NR-0701), and others are advancing in new Alzheimer’s drug developments. Aribio entered Phase 3 clinical trials in the United Sates…GemVex has concluded Phase 2 clinical trials in Korea and is preparing for global clinical trials. According to the industry on the 6th, Aribio submitted a European IND application on the 26th of last month for the approval of a global Phase 3 clinical trials called ‘Polaris-AD’ for AR1001. The European clinical trials will enroll 400 patients with early Alzheimer’s disease from eight European countries, including the U.K., France, Germany, Spain, Italy, Denmark, Netherlands, the Czech Republic, and Slovakia. AR1001 utilizes multimodal mechanisms to target the underlying causes of Alzheimer’s disease, such as PDE5 and toxic proteins. In 2022, Phase 3 clinical trials were initiated in the United States, and these trials are recruiting patients and administering the drug at 60 major clinical sites across the United States. Samjin Pharmaceutical holds exclusive sales rights for AR1001 in Korea. Samjin Pharmaceutical and Aribio have signed a joint development of Phase 3 trials in Korea, as well as the exclusive sales rights for the domestic market. Both companies are currently conducting Phase 3 trials in Korea. In Phase 2 clinical trials, AR1001 demonstrated therapeutic effects in patients with elevated levels of blood pTau-181, a significant factor associated with Alzheimer’s disease. Additionally, the AR1001 10mg cohort demonstrated a decrease in cognitive decline compared to the placebo group, while the AR1001 30mg cohort demonstrated enhancements in cognitive abilities related to pattern recognition. GemVex is currently developing GV1001, a candidate multimodal treatment for Alzheimer’s disease. GV1001 has successfully concluded the Korean Phase 2 clinical trials and is preparing for global Phase 2 clinical trials. GV1001 binds to the Gonadotropin-releasing hormone receptor (GnRHR) expressed in microglia and astrocytes, effectively suppressing neuroinflammation. By binding to GnRHR, present on these two cell types, GV1001 functions as a cytokine that modulates brain immune responses. GemVex will conduct simultaneous clinical trials in seven European countries using the Phase 2 clinical trials IND application submitted to the FDA. The clinical trials will evaluate the therapeutic effects and safety of the drug with 185 moderate to severe patients administered with doses of 0.56 mg and 1.12 mg over 52 weeks. CHA Biotech is conducting Phase 1/2a clinical trials for its new drug candidate CB-AC-02. CB-AC-02 is a stem cell therapy utilizing placenta-derived mesenchymal stem cells and is under development using mass culture and cryopreservation techniques. NKMAX is currently developing the cell therapy SNK01 through its subsidiary NKGen Biotech. The company has successfully completed the drug administration to patients enrolling in the Phase 1/2a clinical trials. SNK01 is designed to recognize and eliminate reactive T cells and damaged neurons, thereby reducing neuroinflammation and improving the overall brain immune system. In the Phase 1 clinical trials conducted in Mexico, NKGen Biotech’s SNK01 demonstrated the therapeutic effects in patients with moderate to severe Alzheimer’s disease. Three out of ten patients who were administered SNK01 showed improved symptoms in the AD Composite Score (ADCOMS), while six patients showed no change without further deterioration. Furthermore, the FDA has granted permission to continue the Phase 1/2a clinical trials without requiring preclinical trials, based on the results obtained from the Mexico Phase 1 clinical trials. Neurorive and Shaperon, completing pre-clinical trials, aim to enter a late phase of clinical trials. Shaperon is developing NuCerin for treating patients with moderate to severe Alzheimer’s disease. NuCerin is designed to inhibit microglia and TNF-α production and under development to alleviate neuroinflammation. NuCerin is currently in the Korean Phase 1 clinical trials. Nucerin demonstrated no Dose Limiting Toxicities (DLT) up to the third level of dosage during the trial, following a dose escalation design. Additionally, Shaperon signed a technology transfer contract with Kukjeon Pharmaceutical in March 2021. Neurorive is currently conducting Korean Phase 1 clinical trials for their candidate product NR-0701. NR-0701 utilizes acetylcholinesterase and phosphodiesterase (PDE) inhibitors, which are the active ingredients found in medications like Donepezil, used for Alzheimer’s disease, and Viagra, respectively. Through this mechanism, Neurorive aims to achieve effects that are comparable to increased therapeutic effects of Alzheimer's disease drug Donepezil while simultaneously reducing the toxicity associated with Viagra-class drugs, maximizing neurotransmission capacity.
- Company
- GC Biopharma says its ‘Shingrix vaccine shows effect in P2T
- by Lee, Seok-Jun Jan 09, 2024 05:49am
- GC Biopharma (CEO Eun-cheol Heo) today announced positive Phase 2 results for its shingles vaccine, CRV-101 (ingredient name amezosvatein),’ which is being developed by its U.S. partner Curevo Vaccine. The data represent top-line results from a head-to-head comparison of GSK's market-leading shingles vaccine, Shingrix, and CRV-101, which meets all primary endpoints and demonstrated non-inferiority and superior tolerability to GSK’s shingles vaccine Shingrix. To evaluate the immunogenicity and safety of CRV-101, Curevo Vaccine inoculated 876 healthy adults aged 50 years and older with two different vaccines, at 2-month intervals, as the second booster shot. The results showed that CRV-101 met its primary endpoint, demonstrating non-inferiority to Shingrix through humoral immune responses. The Vaccine Response Rate (VRR) for CRV-101 was 100%, compared to 97.9% for Shingrix. The Phase 2 results provided a basis for dose selection, which Curevo plans to build upon to initiate a Phase 3 study later this year. CRV-101 is a premium herpes zoster vaccine developed by genetic recombination with an immune-boosting adjuvant. It is designed to induce an optimal immune response with a low risk of side effects. According to the global market research firm Evaluate Pharma, the global market for shingles vaccines is expected to reach $5.85 billion by 2028, including the U.S. market.
- Policy
- Data Exclusivity Bill for IMDs may soon be legislated
- by Lee, Jeong-Hwan Jan 09, 2024 05:49am
- A bill to amend the Pharmaceutica Affairs Act, which grants a 6-year data exclusivity for incrementally modified new drugs that have obtained domestic marketing authorization, was reviewed during the plenary session of the Legislation and Judiciary Committee that was held on the afternoon of the 8th. If approved by the committee, the bill will be passed during the plenary session tomorrow (Sept. 9) and be legislated. The bill also suggest abolishing the drug re-review system and replacing it with a risk management plan (RMP). In particular, there is great interest in the new provision in the bill that recognizes exclusive rights to new and incrementally modified drugs and protects clinical trial data submitted at the time of drug approval. Specifically, the bill provides 10 years of protection from the date of approval for orphan drugs. This can be extended by an additional year if a pediatric indication is added. New drugs are granted 6 years of data exclusivity from the date of approval, and drugs that submit new clinical trial data, such as cto hanging the type of active ingredient to improve the safety, efficacy, and utility of already approved drugs, are granted 6 years of exclusivity from the date of approval. Based on this provision, IMDs can be granted a 6-year data protection period based on the provision. In addition, drugs designated by the Prime Minister's Decree that require submission of new clinical trial data are granted a 4-year data protection period. The existing reexamination system provides 10 years of data protection for orphan drugs, 6 years for new drugs and drugs with new active ingredients, formulation ratios, and routes of administration, and 4 years for new drugs with new efficacy and effect. If the bill passes the National Assembly, it is expected the data exclusivity of IMDs developed many domestic pharmaceutical companies will be recognized, Teh bill provides exclusivity when developing improved versions of their existing drugs, especially in terms of fficacy or utilit, with raises possibility of the development of a cash cow during new drug development. The bill is likely to pass the National Assembly because the Ministry of Food and Drug Safety (MFDS) is in favor of it and has been involved in its legislation, and it is in line with the government's policy of creating domestic blockbuster drugs. The MFDS said, "We agree with the purpose of the amendment to reduce the burden of data submissions to the pharmaceutical industry by integrating the drug reexamination system and risk management system, and to enhance Korea R&D capabilities in the pharmaceutical industry by establishing a legal basis for the drug data protection system."
- 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.”
- Company
- Recent tech export deals boast record-high upfront payments
- by Chon, Seung-Hyun Jan 09, 2024 05:49am
- Since the end of last year, Orum Therapeutics, Chong Kun Dang Pharmaceutical (CKD Pharm), LegoChem Biosciences, and others have successfully secured large-scale technology transfer agreement with an upfront payment of 100 billion won. Out-licensing contracts with upfront payment scale over 10% of the total contract value have been on the rise due to the high value of technology exports for new drugs. According to the industry on the 9th, LG Chem signed a technology transfer agreement with Rhythm Pharmaceuticals on the 5th for a rare obesity drug candidate LB54640. Under the agreement, Rhythm Pharmaceuticals will acquire the global development and sales rights of LB54640. LB54640 is the world's first oral MC4R agonist, and the results of its Phase 1 clinical trials have shown a dose-dependent trend in weight loss and safety. LB54640 successfully completed Phase 1 clinical trials and commenced Phase 2 clinical trials in October. Rhythm Pharmaceuticals will acquire the rights to LB54640 and continue its development. Under the agreement, the price for technology transfer amounts up to $305 million (about 400 billion won), including the upfront payment of $100 million (approx. 130 billion won). The upfront payment of $100 million is the third-largest in technology transfer agreement for a new drug signed by a Korean pharmaceutical firm. Recently, in the technology transfer agreements of pharmaceutical and biotech firms (including Hanmi Pharm, SK Biopharmaceuticals, LG Chem, LegoChem Biosciences, Orum Therapeutics, Chong Kun Dang Pharm, and others), upfront payments have been a substantial component of the total contract value. (Source: Financial Supervisory Service, Pharma companies) The highest record of upfront payment for technology transfer agreements is held by Hanmi Pharm. In Nov. 2015, Hanmi Pharm signed a technology transfer agreement for three new diabetes drugs with Sanofi, which initially involved an upfront payment of approximately EUR 400 million. The contract was later revised, reducing the upfront payment to EUR 204 million, but it still stands as the highest upfront payment in such agreements. Hanmi Pharm also holds the record for the second-highest upfront payment with $105 million in an agreement with Johnson & Johnson’s Janssen for its obesity drug in 2015. The upfront payment of $100 million in a technology transfer agreement between SK Biopharmaceuticals and Arvelle Therapeutics for cenobamate, an anti-epileptic drug, ranks third to date. Recently, LG Chem also secured the third in rank with an upfront payment of $100 million in a technology transfer agreement for a new drug, LB54640. The technology export contracts that were finalized since the end of last year have ranked among the top contracts in terms of upfront payments. Orum Therapeutics signed a technology transfer agreement with BMS for the new candidate product ORM-6151 in Nov. 2023. The total contract value was set at a maximum of $180 million, which included the upfront payment of $100 million. ORM-6151 is a candidate product developed utilizing the antibody-based protein degradation platform of Orum Therapeutics. It has received approval for Phase 1 clinical trials from the U.S. Food and Drug Administration (FDA) as a potential treatment for myeloid leukemia and high-risk myelodysplastic syndromes. LegoChem Bio also finalized a technology transfer agreement with an upfront payment of $100 million. In December of the previous year, LegoChem Bio signed a technology transfer agreement with Janssen Biotech for the development and commercialization of "LCB84." The contract included an upfront payment of $100 million (approx. 130 billion won), an additional $200 million (approx. 260 billion won) payment for the exclusive development rights, and further milestone payments linked to development, approval, and commercialization, amounting to a total of up to $1.7 billion (approximately 2.24 trillion won). LCB84 is an Antibody-Drug Conjugate (ADC) drug that combines LegoChem Bio's next-generation ADC platform technology with the Trop2 antibody technology acquired from Mediterranea Theranostic. CKD Pharm signed a technology transfer agreement with Novartis for the new drug candidate CKD-510 in Nov. 2023. The non-refundable upfront payment for this agreement was $80 million, ranking seventh to date. Including milestones of $1.225 billion based on development and approval stages, the total contract size amounts up to $1.35 billion. CKD-510 is a new drug candidate developed by CKD Pharm, utilizing a highly selective non-hydroxamic acid (NHA) platform technology-based HDAC6 inhibitor. Recently, in the technology transfer agreements of pharmaceutical and biotech firms, upfront payments have been a substantial component of the total contract value. LG Chem's LB54640 technology transfer agreement had an upfront payment that accounted for 32.8% of the total contract value, which is a significantly higher proportion than the usual practice where upfront payments typically do not exceed 10% of the total contract value. LG Chem explained that this high value reflects the positive assessment of LB54640's growth potential by their technology transfer partner. Orum Therapeutics received an upfront payment of $100 million, which accounted for 55.6% of the total contract value in their technology transfer agreement with BMS last year. However, Orum Therapeutics' technology transfer involved the transfer of a new drug candidate, which contributed to the larger upfront payment. Typically, pharmaceutical companies receive milestone payments based on the progress of development in technology transfer agreements. In this case, Orum Therapeutics chose to transfer rights and received a larger upfront payment. Hanmi Pharmaceutical's technology transfer agreement with Sanofi for three diabetes drugs, holding the record for the highest upfront payment, had an upfront payment representing 10.3% of the total contract value. However, Hanmi Pharmaceutical and Sanofi's technology transfer agreement saw a reduction in contract size through a revised contract, with the upfront payment ratio decreasing to 7.2%. In 2015, Hanmi Pharmaceutical's technology transfer to Janssen for an obesity and diabetes treatment recorded a high upfront payment ratio of 11.5%. Despite being in the early stages of development, the technology transfer partner assessed the candidate substance with high value. In 2019, SK Biopharmaceuticals entered into a technology transfer agreement with Arvelle Therapeutics for cenobamate, and the upfront payment representing 18.9% of the total contract value. At that time, cenobamate was already in the process of FDA review in the United States, indicating a high likelihood of commercialization, which contributed to the substantial upfront payment in the agreement. The proportion of upfront payments to the total contract value for CKD Pharm and LegoChem Biosciences accounted for 6.1% and 5.9%, respectively. The analysis suggests that the high upfront payments were made because the partnering companies have made positive assessments of new drugs, even though they are in the early stages of clinical trials.
