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- 2026-04-10 13:59:41
- Opinion
- [Reporter's view] The goal of global new drug development
- by Hwang, Jin-joon Mar 28, 2023 05:54am
- When the government announced the 'Third Five-Year Comprehensive Plan to Foster and Support the Pharmaceutical Bio Industry', it was emphasized that it would create three new blockbuster drugs that record global sales of more than 1 trillion won by 2030. For this purpose, strategic R&D investment was selected as a key task. In the development of new drugs, it is planned to significantly increase public and private R&D investment. Looking at the detailed support measures, the government plans to promote R&D investment of a total of 25 trillion won jointly with the private sector for 5 years with 10 global new drug development goals. The government also expects to invest 4 trillion won in government R&D and 21 trillion won in private R&D from this year to 2027. Based on the national new drug development project that inherited the results of the pan-governmental new drug development project from 2011 to 2020, a joint public-private investment of 2.2 trillion won was invested to develop one new blockbuster drug and three new drugs by 2035. A plan for development was also established. The government's will to foster the industry is positive, but the problem with new drug development is that speed is not important. As of last year, there were zero blockbuster new drugs recognized by the government. The government expects to secure two by 2027. Under the current circumstances, only Yuhan's non-small cell lung cancer drug Leclaza and SK Biopharmaceuticals' epilepsy drug Xcopri appear to be the only drugs developed by domestic biopharmaceutical companies by 2027 that have the potential to become global blockbusters. Leclaza was transferred from Genosco/Oscotec to Yuhan Corporation in July 2015 when preclinical development was underway. In November 2018, the technology was transferred from Yuhan to Janssen, a subsidiary of J&J, a global pharmaceutical company. Yuhan received conditional approval for Leclaza as a treatment for secondary mutations in non-small cell lung cancer in Korea in 2021. In other words, it took five and a half years from preclinical trials to conditional approval. It seems that it will take more time for Leclaza to rise to prominence as a global blockbuster. Janssen, which holds the global copyright, is conducting a phase 3 trial of Leclaza alone and Rybrevant as an indication for non-small cell lung cancer. Cenobamate started with basic research in 2001, went through clinical trials and licensing, and was approved by the U.S. Food and Drug Administration (FDA) in 2019. It took 18 years from the first research to enter the large-scale US pharmaceutical market. Last year, US sales of Cenobamate more than doubled from the previous year to 169.2 billion won, but it will take more time to get on the list of global blockbuster new drugs. Moderna's Corona 19 mRNA vaccine, which recorded $18.4 billion in sales last year, was praised for succeeding in developing it in about a year, but the actual situation is different. Moderna's COVID-19 mRNA vaccine is the product of 30 years of RNA research, 20 years of LNP development that protects mRNA, and 10 years of Moderna's own research and development. The government recognized the biopharmaceutical industry as a 'future food in a low-growth period', a 'key field for securing jobs', and an 'essential national strategic industry for overcoming infectious diseases and other diseases and guaranteeing public health'. In order to realize this, not only R&D support measures such as active support for global clinical trials but also support measures for basic research fields such as chemistry and biotechnology from a long-term perspective must be prepared.
- Opinion
- [Reporter's view] Tagrisso's first benefit
- by Mar 27, 2023 05:56am
- AstraZeneca's lung cancer drug Tagrisso has begun receiving benefits for first-line treatment. After 5 challenges, he passed the HIRA Cancer Disease Review Board. After adding the first treatment indication in December 2018, Tagrisso actively tried to expand benefits but was rejected by the review committee every time. The reason was that looking at the data of the phase 3 sub-analysis, the effect of improving overall survival in Asians could not be confirmed. The controversy over the efficacy of Tagrisso was started by Japan and ended by Japan. In the phase 3 FLAURA clinical trial, Japan had the greatest impact in making the OS values of Asians insignificantly different from those of the control group. The medical environment where drug switching is free is a crazy aftermath. The real damage was seen by Korean patients. In Japan, the first benefit is applied regardless of the results of the sub-analysis, but in Korea, because of this data, they had to receive treatment without benefit for more than 4 years. It is also Japan that has quelled OS doubts in Asia. Last year, Japan's large-scale real-world data came out. Real-world data is not clinical in a controlled environment, so it is generally less effective than data from clinical practice. However, Tagrisso showed a longer progression-free survival period and an overall survival period of more than 3 years compared to the phase 3 trial in the Japanese real world. There is no longer any need to argue over phase 3 sub-data. Already, the first-line Tagrisso therapy has fully established itself as a global trend for EGFR-mutated non-small cell lung cancer. A German professor of hemato-oncology whom I met in an interview last year expressed some disapproval at the reporter's question, "What do you think of the sequential treatment that uses the first and second generations first and then the third generation?" This is because I had never thought about sequential therapy after Tagrisso. His answer was, "I heard that even in Germany, a small number of hospitals choose sequential treatment. However, since Tagrisso has already become the clear first-line standard treatment, to be honest, I have never thought about sequential treatment. I'm sorry I couldn't give you an answer. it was" It will take a little longer for Tagrisso to become the standard first-line therapy in Korea. Concern about cancer is just the beginning of reimbursement for anticancer drugs, and in the future, drug price negotiations with the HIRA and the NHIS, and the Ministry of Health and Welfare must all pass. Now it's a speed battle. Depending on how long it stays on the drug rating, the Tagrisso benefit expansion could be over the year or within the year. First of all, AstraZeneca has a very high will to cooperate with the government as much as possible and expedite the process. The HIRA also has many new drugs to review for reimbursement adequacy. But it's only 4 years. The fact that the first petition for Tagrisso's salary exceeded 50,000 people can be said to have reached its maximum level of desperation. I hope that their wait will not exceed 5 years.
- Company
- Pfizer Korea dividend KRW 12.48M, net profit KRW 119.5B
- by Chon, Seung-Hyun Mar 27, 2023 05:56am
- Despite posting record-breaking performance last year, Pfizer Korea’s dividend was set at only KRW 12.48 million. The company adhered to its dividend policy of ’20% preferred stock’ regardless of its performance. According to the Financial Supervisory Service (FSS), Pfizer Korea set its dividend payout for the last year as KRW 12.48 million. With the decision, the company’s dividend payout has now remained the same at 12.48 million for five consecutive years. # i1 The dividend was calculated at the same level as before even though Pfizer Korea’s performance improved significantly due to sales of COVID-19 drugs last year. Pfizer Korea’s sales increased 90.4 YoY from KRW 1.694 trillion to KRW 3.225 trillion last year. Its operating profit more than doubled from the previous year to reach KRW 120.1 billion. Sales of its COVID-19 vaccines and treatments raised the company’s sales performance. Its sales had risen over fourfold in two years from KRW 391.9 billion in 2020, and profitability also improved significantly from its operating loss of KRW 7.2 billion in 2020. The company’s net profit also increased 24.0% YoY to reach KRW 119.5 billion. In general, companies pay out dividends to shareholders proportionate to their increase in net profit. However, Pfizer’s dividend remained the same at KRW 12.48 million as in the previous year, and its dividend payout ratio was a mere 0.01%. Pfizer Korea calculated its dividend by applying a 20% dividend rate to its preferred stock capital. Pfizer Korea’s total capital is KRW 922.92 million. Among them, the common stock capital (172,104 shares) is KRW 860.52 million, and the preferred stock capital (12,480 shares) is KRW 62.4 million. Therefore, with a 20% preferred stock, the dividend was set at 20% of the KRW 62.40 million, at KRW 12.48 million. Pfizer Korea’s largest shareholder is Pfizer’s Dutch subsidiary, 'PF OFG South Korea 1 B.V,’ which owns 99.99% of the shares. Therefore, PF OFG South Korea 1 B.V., which owns all of the company’s preferred stock, will be receiving a dividend of KRW 12.8 million. Pfizer Korea had paid dividends of KRW 12.48 million based on the same standard of '20% preferred stock' for all but two occasions over the past 20 years since 2003. In 2017, its dividends were set at KRW 79.79 billion, which was higher than its net profit. At that time, the dividend rate was set at 660% of the face value of KRW 5,000 for both its common stocks (2,455,520 shares) and preferred stocks (12,480 shares), increasing dividends. In 2008, the dividend was set at KRW 190 billion. Even though the company recorded a deficit of KRW 600 million at the time, the high dividend was determined based on a dividend rate of 3045% compared to face value. Over the past 20 years, these two were the only occasions the company set high dividends, and it upheld its small dividend policy of KRW 12.48 million during the rest of the period.
- Policy
- Jeil Pharmaceutical discontinued Actos co-promotion
- by Lee, Tak-Sun Mar 27, 2023 05:56am
- Actozon 15mgJeil, which has already launched sales of the generic drug Actozone 15mg and the combination drug Actozonemet 15/850mg from 4Q last year, is expected to launch Actozon 30mg in the reimbursement market in April. According to the industry on the 26th, Actozon 30mg will be listed at the upper limit of 940 won from April 1st. There are still fewer than 19 generic drugs listed, and Jeil Pharmaceutical succeeded in calculating the same price as the highest price by meeting all the standard requirements. Previously, when Actozon 15mg was re-listed in January of last year, it was difficult to calculate the highest price as there were more than 20 generics. Accordingly, Actozon 15mg has been listed at the lowest price of 359 won for the same product. Actozonemet was also listed at the highest price of 714 won when it was re-listed in August of last year, as fewer than 19 identical drugs were listed. In terms of drug price, apart from 15mg, single drugs 30mg, and combination drugs maintain the highest price, and it is evaluated that they did well even though they entered the generic market belatedly. Jeil entered the generic market belatedly because the co-promotion of the original Actos and Actos met, which had been sold since the second half of last year, was discontinued. Best has sold Actos since 2013. At the time, it signed a co-promotional contract with Takeda. Jeil had to end 9 years of original sales as Celltrion Pharm took over the Asia-Taeyang region rights for Takeda products including Actos last year and started selling them alone from the second half of the year. Jeil immediately put generics into the market. In January of last year, Actozon 15mg, which had been removed from reimbursement, was listed again on the list of benefits, and in August of that year, Actozonemet was also listed again. Then, from the fourth quarter of last year, generic drugs were sold in earnest. Actozon 30mg was additionally approved in January. From April, it is expected to enter the market in earnest with a full lineup of pioglitazone capacities. As Jeil secured a large number of customers by selling the original Actos, it is expected that the relationship with customers lost due to the suspension of product sales in the generic business will be restored in the short term. The three-drug regimen including Metformin + SGLT2 will be covered from April for Glitazone drugs, which is also positive for sales recovery. An official in the pharmaceutical industry said, “As Jeil has a long experience in selling Actos, it is highly likely that it will quickly settle into the market as a generic drug.” He explained, "Therefore, other generic companies are also watching Jeil's movements."
- Company
- SGLT-2 combo Qtern awaits release in Korea
- by Eo, Yun-Ho Mar 27, 2023 05:56am
- With reimbursement extensions to combination therapies that use SGLT-2 inhibitors imminent, the combination drug ‘Qtern’ is rapidly landing at general hospitals in Korea. According to industry sources, AstraZeneca’s DPP-4i+SGLT-2i Qtern (saxagliptin+dapagliflozin) which is being solely distributed by Ildong Pharmaceutical in Korea, has passed the drug committee (DC) reviews in tertiary hospitals such as Seoul National University Hospital, Seoul St. Mary’s Hospital, Seoul Asan Medical Center, Sinchon Severance Hospital, and other general hospitals including Gangwon National University Hospital, Korea Anam University Hospital, Nowon Eulji Medical Center, Ewha Womans University Medical Center, Inje University Ilsan Paik Hospital, Chonnam National University Hospital, Jeju National University Hospital, Chungnam National University Hospital, and Hanyang University Guri Hospital. Although the drug had been approved in March 2017, it was not released in Korea due to the non-resolution of the reimbursement issue for antidiabetic combination therapies in Korea. However, However, Qtern may finally be released in line with the progress made regarding the government’s discussions on antidiabetic combination drugs and the reimbursement standards being expanded for antidiabetic combination therapies from next month (April). Qtern is currently undergoing reimbursement listing in Korea. Other DPP-4+SGLT-2 combination drugs that are approved in Korea include Boehringer Ingelheim’s ‘Esglito (linagliptin+empagliflozin)’ and MSD’s ‘Stegluzan (sitagliptin+ertogliflozin).’ These drugs are also awaiting the revitalization of the combination market that will come with the resolution of the reimbursement issue. Generic versions of antidiabetic combos are also awaiting entry into the market. The post-marketing surveillance period for DPP-4i+SGLT-2i combos is soon to expire, until which application for generic drugs is blocked. Meanwhile, in a Phase III trial that studied adding dapagliflozin or placebo to the saxagliptin+metformin two-drug combination therapy for 52 weeks, results showed that patients that used the three-drug combination showed an improvement in terms of lowering blood sugar level and achieving glycosylated hemoglobin (HbA1c) target level over the two-drug combination therapy. No hypoglycemia side effects were additionally observed in the study.
- Policy
- Dupixent 200mg, newly listed
- by Kim, Jung-Ju Mar 27, 2023 05:55am
- Sanofi-Aventis Korea's severe atopic dermatitis treatment Dupixent PFS 300mg has expanded insurance coverage to pediatric and adolescent patients, and products with 200mg content will be newly listed next month with an expanded range. Taking this as an opportunity, the government is planning to expand the scope of benefits for special calculations based on eliminating blind spots in existing treatments for severe atopic dermatitis. Janssen Korea Erleada, which is used for the treatment of metastatic prostate cancer (mHSPC), will be newly listed as a risk-sharing contract (RSA) reimbursement type at around 20,000 won. According to the industry on the 21st, the Ministry of Health and Welfare plans to revise the 'drug reimbursement list and reimbursement upper limit table' and is pushing to apply it on the 1st of next month. There are a total of 4 new drugs being promoted, 1 drug that has been expanded in the scope of use (benefit), and 4 items that are under contract renewal negotiations with the NHIS due to the expiration of the RSA period. ◆Newly listed item = Erleada is newly listed next month at 20,045 won so that it can be applied for health insurance. This drug is used in combination with androgen deprivation therapy (ADT) for the treatment of patients with hormone-responsive metastatic prostate cancer. Currently, A7 is registered in a total of seven countries, including the United States, Japan, France, Germany, Italy, Switzerland, and the United Kingdom. The company applied for insurance listing to the Review and Assessment Service on November 30, 2021, a year later. proceeded. At the time, the committee judged that the cost-effectiveness ratio was included in the acceptable range as a result of the economic evaluation, but the reimbursement was appropriate when the drug price was lowered in consideration of the financial impact such as the possibility of an increase in market share. As the company accepted this result, the drug was put on the negotiating table of the NHIS, and immediately entered into negotiations on the drug price and expected billing amount, and was successfully registered in April. The corporation expects that this drug will be cheaper than alternative treatments, and actual additional finance will be insignificant when considering the RSA refund rate in the future. Dupixent, which is used for severe atopic skin disease in adults, is also listed as a 200mg product with reduced content. Similar to the 300mg content product already registered and covered by insurance, RSA refund type, total amount limit type, and initial treatment cost refund type were applied to this content product in combination. In addition, Bukwang Pharmaceutical's Zaledeep 5mg and 10mg content products, which have stepped on the track of skipping drug price negotiations with the NHIS, are also listed at 102 won and 153 won per capsule, respectively. ◆ Expansion of scope of use = The scope of reimbursement for Dupixent 200mg, which is already registered, will be expanded from adults currently applied to children and adolescents in the future. Currently, it is estimated that 5,000 Korean adults with atopic dermatitis are receiving benefits. The government plans to broaden the reimbursement standard so that the drug can be widely used for children (6-11 years old) and adolescents (12-17 years old) with atopic dermatitis. The number of these patients is estimated to be 2550. The drug's benefit for children and adolescents is being applied to all A7 countries, and it is also being applied to adults in Korea, so its clinical usefulness has already been proven. Following the increase in benefits this time, the company negotiated with the NHIS again and set the price at 696,852 won per share, a 1.5% cut. At the same time, the government expands the scope of application of special calculations accordingly. It is to adjust the benefit standard while expanding the benefit from the existing adult target to children and adolescents. This is because if the current registration standards for calculation special cases are maintained, pediatric patients fall under the pharmaceutical reimbursement standards, but cannot meet the registration standards for calculation special cases, creating a blind spot where special cases are not applied. ◆ RSA Expiration Evaluation Items = Negotiations were made to renew contracts for 4 items of drugs covered by insurance through RSA. The target is Cabometyx, a renal cell cancer drug from Ipsen Korea, and Erbitux Inj. 5mg/mL (cetuximab), colorectal cancer, and head and neck cancer treatment from Merck. Before the contract period of the RSA drug expires, the government has the Pharmaceutical Review Committee evaluate the drug's clinical usefulness and cost-effectiveness, and proceed with contract renewal negotiations with the NHIS. The types of negotiations include lower drug prices, expected billing amounts, reimbursement rates, and caps. The target drugs for this time were contracts with Cabometyx or Erbitux, which limit the amount of use per patient, and as the companies expressed their intention to renew the contract, the procedure was followed. As a result of the negotiations, Cabometyx will be cut by 2.5% for each content, and Erbitux will be cut by 8.5%. In the case of Erbitux, the new drug price will be applied as of May 1 due to the renewal of the contract.
- Policy
- Forxiga patent is about to expire
- by Kim, Jung-Ju Mar 24, 2023 05:48am
- As the patent for Dapagliflozin, the original drug (Forxiga), is about to expire, domestic generics of this drug will be released early next month. Accordingly, the government is swiftly proceeding with the process of calculating the drug price and additional negotiations so that the drug can be listed immediately. According to the industry on the 21st, the Ministry of Health and Welfare is planning a revision of the drug reimbursement list and the maximum reimbursement amount table and is pushing to apply it on the 1st of next month. The application date is April 8, the day after the patent expiry date of Forxiga. Forxiga is an antidiabetic drug, and its price dropped to 734 won, or 3.4%, after negotiations with the NHIS for PVA type "Na" was concluded on the 13th. Domestic generics, which are taking a breather to secure market share, are 89 single drugs and 78 combination drugs. The Ministry of Health and Welfare has calculated generic drug prices based on 734 won, which was set as a result of PVA negotiations, in order to quickly register these drugs. If the original drug expires, the generics are automatically given a price calculation of 53.55%. Currently, companies ahead of the launch of Forxiga's generics are currently in the process of negotiating with the NHIS for stable supply and quality control while preparing for enlistment on the 8th. The deadline for negotiations is the 30th of this month. Governments and authorities expect generics to quickly capture half of the claims once they hit the reimbursement market. The estimated size of fiscal savings is expected to be around 1.1 billion won per month. Estimated on an annual basis, it is about 13.2 billion won. As the share of domestic products increases, the reduction in health insurance finances is proportional to that amount, so the government has no choice but to be busy.
- Policy
- Dual punishment for CSO rebates passes NA committee
- by Lee, Jeong-Hwan Mar 24, 2023 05:48am
- A provision that stipulates the prohibition of doctors from receiving rebates offered by contract sales organizations (CSOs) and a plan to amend the Medical Service Act to advance regulations on medical advertisements and allow the Ministry of Health and Welfare to intervene in the Medical Advertisement Deliberation Committee passed the plenary meeting of National Assembly’s Health and Welfare Committee. Also, a proposal to amend the Pharmaceutical Affairs Act, which includes a clause prohibiting illegal hospital subsidies in exchange for prescriptions between hospitals and pharmacies that are preparing to open, and a clause that allows pharmacists to refuse to dispense poor or counterfeit narcotics prescriptions was passed in the same the plenary meeting. Also, the bill to manage the harm from cigarettes, which was merged as an alternative by the NA Chair after the bill was separately presented by NA Rep. Hye-Young Choi of the Democratic Party of Korea and Ki-Yoon Kang of the People Power Party, also crossed the threshold set by the Health and Welfare Committee. On the 23rd, the NA Health and Welfare Committee. held a plenary session and voted on the bills that were reviewed by the 1st and 2nd legislation subcommittees. A bill that adds drug CSOs to the scope of rebates such as money and valuables that doctors should not receive and obligates the medical device CSOs to report to the government and local governments passed the Health and Welfare Committee deliberations. Therefore, these agendas will go through legislative procedures with the drug CSO reporting system that had been pending at the Legislation and Judiciary Committee level. Changes are expected in the review of medical advertisement deliberations in the future as the Medical Advertisement Deliberation Committee, which consists of functional groups of medical professionals such as those from the Korean Medical Association, passed the bill to improve MDAC deliberations and allows the Ministry of Health and Welfare the right to intervene. Also, the Pharmaceutical Affairs Act, which prohibits prospective hospitals and pharmacies from exchanging hospital subsidies for prescriptions, is subject to review by the NA’s Legislation and Judiciary Committee. Furthermore, legislation of the Tobacco Hazard Control Act, which includes disclosure of the types and amounts of harmful substances contained in e-cigarettes as well as leaf tobacco is expected to accelerate progress. Also, an amendment to the Narcotics Control Act that stipulates that pharmacists at pharmacies may refuse to dispense drug prescriptions issued by medical institutions that poorly entered patient information or are suspected a forgery also passed the Health and Welfare Committee. Whether to present the bills at the plenary session will be determined by the Legislation and Judiciary Committee after considering the agenda seriatim.
- Company
- Discussion of reimbursement for Vyndamax is running in place
- by Eo, Yun-Ho Mar 24, 2023 05:48am
- It seems that discussions on registration of transthyretin (TTR) amyloid cardiomyopathy drug 'Vindamax' for insurance benefits are at a standstill again. As a result of the coverage, Pfizer Korea's ATTR-CM (ATTR amyloidosis with cardiomyopathy) treatment Vyndamax, (Tafamidis 61mg) passed the HIRA last year, but the schedule for presentation to the Pharmaceutical Reimbursement Evaluation Committee has not yet been set. there is. In fact, it is judged that the discussion has ceased. The passage of the standard subcommittee itself was the result of only the fourth challenge, but it disproves that the gap between the government and pharmaceutical companies remains. Vyndamax failed to designate an essential drug in its first reimbursement challenge in early 2021. Afterward, an economic evaluation was conducted in the first half of the same year and a second challenge was reached through a Risk Sharing Agreement, but the results were the same. And in April of last year, it failed to exceed the standard subcommittee again, but in the second half of last year, it barely made a step forward. However, it is judged that there were still difficulties in finding a point of agreement in terms of financial sharing. It remains to be seen whether Vyndamax will be able to supplement the data again and continue discussions on salary listing. Meanwhile, Vyndamax is virtually the only ATTR-CM treatment option. ATTR-CM has been regarded as a disease with poor treatment results because it is misdiagnosed as simple heart failure or has no treatment, even though it is fatal enough that the survival period is only 2 to 3.5 years if not treated appropriately. In this situation, Vyndamax is a drug that has been shown to reduce the occurrence of cardiovascular events in CM patients through the phase 3 ATTR-ACT study and to improve the 6-minute walking test. In the ATTR-ACT study, 441 patients have randomized to Tafamidis 80 mg, Tafamidis 20 mg, and placebo in a 2:1:2 ratio. The main secondary endpoints of the study were the change in the 6-minute walk test from baseline to 30 months, the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the KCCQ-OS score, where higher scores mean better health. As a result of the study, the Tafamidis-administered group showed a statistically significantly lower risk of all-cause death and cardiovascular-related hospitalization compared to the placebo-treated group.
- Company
- 5th time the charm for Tagrisso’s reimbursement extension?
- by Jung, Sae-Im Mar 24, 2023 05:48am
- After five attempts, the EGFR mutation-positive non-small cell lung cancer (NSCLC) treatment ‘Tagrisso (osimertinib)’ finally crossed the first hurdle to receiving reimbursement as a first-line treatment. Although other procedures such as deliberation by the Health Insurance Review and Assessment Service’s Drug Reimbursement Evaluation Committee remain, the fact that it had overcome the highest barrier to reimbursement, the Cancer Disease Deliberation Committee review, 4 years after its indication was expanded to the first line, is regarded an achievement. HIRA’s CDDC held its second 2023 Reimbursement Standard Deliberation Meeting for Anticancer Drugs on the 22nd and established reimbursement standards for Tagrisso. The CDDC determined it was appropriate to set reimbursement standards for Tagrisso as a ‘first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.’ With the decision, the drug was able to pass the first gateway for third-generation EGFR-targeted anti-cancer therapies to receive reimbursement as a first-line treatment. ◆Passes CDDC review after 5 attempts...sees fruition 4 years after indication expansion Tagrisso is a third-generation targeted anticancer therapy that targets the EGFR mutation. It inhibits both the EGFR mutation and T790M mutation that are represented by L858R and Exon 19 deletions. As the drug has a high blood-brain barrier (BBB) permeability than first and second-generation EGFR-targeted therapies, Tagrisso has shown a superior effect in patients with brain metastasis. Tagrisso, which added its first-line indication in December 2018 in Korea, attempted to extend its reimbursement to the indication in 2019. However, the drug was unable to receive reimbursement as a first-line treatment for over 4 years. AstraZeneca had attempted reimbursement for Tagrisso at the CDDC level 4 times since 2019 and failed every attempt. When Tagrisso’s reimbursement to the first line first emerged as an agenda in the second half of 2018, the government had been in favor of extending reimbursement. However, the favorable stance faltered with the release of the Asian subgroup analysis results from a global Phase III trial in 2019. The FLAURA trial assessed the efficacy and safety of Tagrisso in the first line, and the Asian subgroup analysis results of this global trial had risen as a barrier to its reimbursement as its hazard ratio (HR) was 0.995. An HR of 0.995 indicates that the difference between Tagrisso and the control group is 0.005, which could be interpreted as the difference being insignificantly small. After such results were disclosed, the CDDC in October 2019 decided to defer its decision until the full data from the Phase 3 FLAURA trial was released. The company made its second attempt, submitting the overall OS data of FLAURA in 2020. However, due to the rapid spread of COVID-19, the CDDC meeting that was set for February of the year had been pushed back and canceled several times and finally held at the end of April. The reimbursement standards for the drug had not been set then either. Although AstraZeneca expressed their will to accept most of the cost-sharing plan proposed by the government in consideration of the Asian subgroup data, the reimbursement fell through due to strong opposition from committee members that raised the issue of the drug’s clinical efficacy. In September of the same year, the company made its third attempt powered by results from the FLAURA China study that confirmed improved OS in Asians. The FLAURA China trial data analyzed a cohort of 136 Chinese patients that included 19 Chinese patients from the global FLAURA trial as well as 117 patients from a trial that had been separately conducted. Results showed that the median PFS of the Tagrisso group was 17.8 months, which was comparable to the results from the global study. Median OS in the Tagrisso group was 33.1 months, 7.4 months longer than the 25.7 months in the control group. This is a higher OS improvement than the 6.8 months identified in the global trial. The third reimbursement extension discussions for Tagrisso were made in April 2021. The third attempt also resulted in failure. At the time, CDDC members concluded that the OS value from the FLAURA China trial lacked statistical significance. After the third attempt failed, patient groups rose to the occasion. After Tagrisso's failure to receive reimbursement in April, 1,713 lung cancer patients and their families sent a joint statement to the government imploring the government to extend Tagrisso’s reimbursement to the first line as in many major countries. Academic societies also criticized how only Tagrisso is not being reimbursed as first-line treatment in Korea. 3 months after its third setback, AstraZeneca applied for the 4th time to extend reimbursement. This time, the company adopted a strategy of narrowing part of its reimbursement standards. The company excluded Exon 21 mutation from the 'EGFR exon 19 deletion or exon 21 (L858R) mutation NSCLC’ it had been indicated for. The company narrowed the criteria to 'first-line treatment for patients with EGFR exon 19 deletion and brain metastases' and reapplied for reimbursement. The plan was to increase the clinical value of the drug by excluding the patient group that showed a relatively small difference in efficacy from the control group. However, Tagrisso’s reimbursement extension was rejected at the CDDC meeting that was held in November 2021. Real-world study on first-line Tagrisso use in Japan. OS results according to gene mutation status (Data: ESMO) This reluctant sentiment on Tagrisso’s reimbursement extension was reversed at the end of last year with the release of large-scale real-world data on Tagrisso’s use in the first line in Asia and Europe. Analysis of real-world data on 660 Japanese patients confirmed a longer progression-free survival period (20.0 months) and an overall survival period of more than 3 years (40.9 months) than those identified in the Phase III trial. With this data, the company put an end to Tagrisso’s efficacy controversy in Asia. AstraZeneca took on its 5th challenge with this new data and a plan to lower drug prices as supplements. The patient organizations’ petition requestion reimbursement extension also added support. The 'Petition regarding the request for first-line treatment of the lung cancer treatment Tagrisso’ that was uploaded to the e-People website in February was sent to the National Assembly Health and Welfare Committee for deliberation after receiving over 50,000 consents. As a result, after 5 attempts in the course of the past 4 years, Tagrisso finally made it through the first barrier to its reimbursement and passed the CDDC review. ◆Can it be reimbursed within the year? Depends on DREC progress Although it has passed the high barrier of CDDC review, many procedures still remain for its reimbursement extension. For anticancer drugs, CDDC review is only the first step of many. The agenda has to pass HIRA’s Drug Reimbursement Evaluation Committee (DREC), and then undergo pricing negotiation with the NHIS, then pass MOHW’s Health Insurance Policy Deliberation Committee (HIPDC) review to complete all the procedures required to extend benefits. Tagrisso is subject to the risk-sharing agreement (RSA) scheme and must pass the pharmacoeconomic evaluation. HIRA’s statuary evaluation period is set to 120 days or less, but it is common for HIRA to exceed the set deadline if the company is required to submit supplementary data. After completing discussions with HIRA and passing DREC review, the company has to conduct drug pricing negotiations with NHIS for up to 60 days. Within 30 days from the period, MOHW’s HIPCD will deliberate and then issue a notification on the new drug price and then list the drug for extended reimbursement. In other words, at maximum, Tagrisso’s reimbursement extension is set to be made by the end of this year. The decisive step in advancing or delaying this timing of Tagrisso's reimbursement is expected to depend on DREC’s stage, where the pharmacoeconomic evaluation takes place. If DREC requests supplementary data repeatedly, reimbursement listing may be delayed indefinitely. In fact, several anticancer drugs have not been deliberated for over a year at the DREC level after passing the CDDC review. In the case of MSD's Keytruda, which succeeded in extending reimbursement to the first-line treatment of NSCLC after 4 years, Keytruda’s reimbursement agenda was presented to DREC 6 months after passing the CDDC review in July 2021. Although the company showed a high willingness to negotiate the reimbursement of Keytruda, the process was only completed eight months after passing the CDDC review due to a delay in its schedule, such as an unsuccessful submission for the DREC review in November 2021. AstraZeneca plans to make the best efforts to extend Tagrisso's reimbursement within the year. The company said, "We welcome the CDDC’s decision and would like to express our thanks to the government and committee members for making efforts to enable this. We will continue to do our best to complete the procedures that remain and receive the reimbursement decision”
