- by Eo, Yun-Ho Sep 30, 2022 05:54am
The pharmaceutical industry raised opposition to the government’s proposed amendment to the insurance reimbursement system.
According to industry sources, the Korea-Research Based Pharmaceutical Industry Association (KRPIA) submitted an opinion statement to the government regarding the pre-announced ‘Proposal for Partial Amendment to the Regulations on the Evaluation Standards and Procedures to Determine Eligibility for Reimbursement Benefits.’
In the statement, KRPIA requested revisions to the special exemption of pharmacoeconomic evaluations exemption system’s ▲‘few patient’ requirement ▲benefits for pediatric patients, etc.
Korea Pharmaceutical and Bio-Pharma Manufacturers Association is also expected to submit a written opinion by the deadline, which is today (30th) to relay the same opinion as KRPIA. The two associations, which usually had different positions on government policies, seem to agree on this case.
First, the KRPIA clearly expressed its opposition to the improvement plan that includes the "few subject patients" as a prerequisite.
The improvement plan brought concern in the industry due to the fact that a major premise for the PE exemptions has also been changed. The condition had previously been an “OR” clause included in Article 2(c) of eligibility for PE exemption regulations, along with other clauses such as ‘if a single-arm study was conducted,’ etc.
The association requested the government to maintain the regulation in its current state. KRPIA said, “Drugs that fall under Item 2(a) and 2(b) that have difficulty generating evidence were eligible for PE exemptions even if they were not used to treat ‘few’ patients. However, the revision mandates the ‘few’ condition to be met. This will only reduce the scope of eligible subjects.”
The association also added that expanding the scope of PE exemption to pediatric patients, which the government had heralded as the purpose of the revision, also needs additional improvements.
The government added a clause allowing PE exemption for ‘drugs used to treat pediatric patients that are therapeutically equivalent or has no available treatment option; and demonstrates improvement in quality of life or is otherwise approved by the committee.’
In essence, the added clause excluded the “life-threatening disease” condition for PE exemptions just for pediatric patients. In other words, if drugs used for pediatric patients satisfy the remaining conditions, the PE exemption may be applied even if the condition is not life-threatening.
However, the industry’s opinion is that the application of the standard should be extended. Through the written opinion, the KRPIA stated, “The government had first discussed expanding coverage to diseases that affect a small number of patients and bring a very poor quality of life even if they are not life-threatening in consideration of the characteristics of rare diseases. However, the benefit expansions made to pediatric patients or just main indications is limited and does not align with the government’s initial purpose.”
To what extent the KRPIA and KPBMA’s opinions will be reflected remains to be seen. The Ministry of Health and Welfare and other subordinate institutions have been cautious about expanding the scope of the PE exemption system.
- Strengthen the guarantee of 21 new drug by the third quarter
- by Kim, Jung-Ju Sep 30, 2022 05:53am
- From January to the third quarter of this year, a total of 21 new drugs were newly listed on the drug benefit list or improved access to use due to expanded insurance benefit standards. Among them, two new drugs were newly listed on the drug benefit list this month. The number of domestic patients estimated to benefit or suffer from the government's policy to strengthen the guarantee of new drugs this year is 1,323,065, and the cost of drugs is 451.75 billion won. In particular, with the emergence of ultra-high-priced drugs that focus on the minority, the government's drug guarantee and accessibility policy are becoming more flexible according to social trends and needs. A total of 21 drugs (based on the representative content) have been strengthened due to the expansion of standards among new drugs and registered drugs that succeeded in listing new drug pay lists from January to this month.
On a monthly basis, Vyzulta and Skilarence were newly registered in February, and Besponsa's standards expanded, and the coverage began to be strengthened. In March, Xospata 40mg and five new osteoarthritis treatments, including Lutathera, Keytruda, Vitrakvi Rozlytrek, newly registered ultra-high-priced treatment kymriah in April, and Tecentriq in May.
Looking at the recent drug coverage, the coverage of Kadcyla, a breast cancer treatment, expanded in the third quarter, starting with the new registration of Fexuclu, a treatment for erosive gastritis.
In August, Zolgensma, a new drug for spinal muscular dystrophy, which was called an ultra-high-priced new drug and attracted social attention for a long time, was newly registered, widening the scope of drug coverage. Zolgensma's estimated number of patients in Korea is only seven but expected demand The cost of drugs reached 13.87 billion won, making it difficult to guarantee for a long time. Nevertheless, the fact that this drug was able to be paid can be said to be the result of our society's flexible expansion of coverage by recognizing the social importance, even if the number of patients is small.
Subsequently, Sonazoid, radiation drugs for PET, Doppa check, Donerion and Dongesive, which are used for Alzheimer's-type dementia, were newly listed, and the standards for prostate cancer treatment Xtandi and urinary tract epithelial cancer treatment Keytruda, which had high patient needs, were expanded.
This month, Pfizer Lorviqua and the chronic migraine drug Emgality succeeded in paying, allowing 350 and 2,344 patients, respectively, to receive benefits. The annual fiscal requirement estimated here is an absolute financial forecast.
Among them, since RSA-applied drugs are calculated based on the indicated price, it is estimated that the actual amount required will be less than this considering the refund rate. In addition, the contents of the contract between the insurer and the company, such as the substitute drug and the sharing of required costs, were not reflected.
- Reevaluation deadline for listed drugs extended 5 months...
- by Kim, Jung-Ju Sep 30, 2022 05:53am
- The government finalized its plan to extend the deadline for reimbursed price reevaluations of listed drugs that are subject to conduct bioequivalence tests and made a final report to the top legislative organization for the national health insurance.
The finalized plan will extend the data submission period of listed drugs that are subject to reevaluations by 5 months, and companies that submit review results during the objection period for the Drug Reimbursement Evaluation Committee’s review after exceeding the submission deadline will also be accepted. The objection period on the Drug Reimbursement Evaluation Committee’s judgment will be around the end of May, and the final announcement period for the drug price cuts is scheduled for December next year.
The Ministry of Health and Welfare held a Health Insurance Policy Deliberation Committee meeting on the 29th and reported the ‘Changes regarding the reevaluation of the upper limit (standards) set for pharmaceuticals.’
The reevaluation of listed drugs was made as a follow-up measure after the introduction of the stepped new drug pricing system that links approvals with drug price to ensure the quality of generic drugs and countermeasures against the flood of generics in the wake of the detection of impurities in valsartan-containing drugs in 2018. Since July 2020, all new generics introduced are applied a stepped pricing system under the new drug pricing system when determining its insurance price. The essence of the standard is to prove the results after conducting in-house bioequivalence tests.
However, due to the spread of COVID-19, the bioequivalence tests that were to be conducted by the companies were not progressable due to difficulty recruiting subjects and the increase of confirmed COVID-19 cases among subjects which led to discontinuation or delays in trials and disrupted system implementation. Industry voices on the need for deadline extensions and deferred evaluations increased further due to the time taken in designating reference drugs necessary to demonstrate the bioequivalence of sterile drug products.
Accordingly, the MOHW and the Ministry of Food and Drug Safety discussed flexibly adjusting the reevaluation procedure and schedule to facilitate smoother operations since May. In comprehensive consideration of the special circumstances that include preserving the consistency in insurance finances and the drug pricing system, equity with new products, and the prolonged COVID-19 outbreak, the MOHW decided to partially modify the data submission deadline and evaluation period, but with the goal of completing the schedule within 2023.
According to the HIPDC report, the data submission deadline for existing items had been extended with a condition in consideration of the COVID-19 situation. The extension will be applied to 10,000 tablet preparations among oral prescription drugs and suppositories that are subject to bioequivalence tests.
Among these drugs, if their bioequivalence tests have been delayed due to COVID-19, etc., the company may submit the test result report to the MFDS by February next year or submit the review results by end of May to HIRA within the planned objection period on HIRA’s Drug Reimbursement Evaluation Committee review, will be deemed to have met the final requirements.
If the companies are unable to demonstrate bioequivalence within the set period, their drug’s price will be reduced as of July 1st next year. Authorities plan to identify progress made for bioequivalence tests by company and month within the second half of the year so that submission of bioequivalence test reports will not be concentrated in a specific period, and encourage prompt data submission to the MFDS upon completion.
Adjustments to the reevaluation period will also follow.
The government will also adjust HIRA's reevaluation period in consideration of the current designation status of reference drugs and MFDS's review schedule. The data submission deadline to HIRA is by July next year, and HIRA's evaluation period will be adjusted from July next year to November. With the changes, the drug price reduction announced for unproven products will be made around December next year.
The MOHW will continue to monitor the progress of bioequivalence tests and the designation status of reference drugs and consult with MFDS and other related associations on issues to guide companies to disperse the submission of their reports.
- development of Korea-Japan, the efficacy of COVID-19 drugs
- by Kim, Jin-Gu Sep 30, 2022 05:53am
- The difference in clinical design from Lagevrio and Paxlovid and the stop of the spread of COVID-19 are also variables. The results of phase 3 clinical trials of Xocova, a candidate for oral COVID-19 treatment under joint development by Ildong Pharmaceutical with Shionogi, Japan, have been announced. In the pharmaceutical industry, it is interpreted that it is one step closer to approval for emergency use in that it has produced meaningful results in shortening the period of symptom improvement, the primary evaluation variable.
Some predict that it is difficult to guarantee Emergency Use Authorization because there is a difference in clinical design from Emergency Use Authorized MSD's Lagevrio and Pfizer's Paxlovid, and there was no permission or approval from the U.S. and Europe.
◆Xocova, similar mechanism to Paxlovid, clinical design is different
Shionogi announced the results of phase 3 clinical trials of Xocova on its website on the 28th. In a clinical trial of 1,821 mild and moderate patients in Korea, Japan, and Vietnam, patients who administered Xocova showed significantly lower time than those who administered placebo until the five major symptoms of COVID-19 (nose congestion, runny nose, sore throat, cough, and fever) subsided. The time to suppress symptoms was 167.9 hours (about 7 days) in the group administered low dose Ensitrelvir and 192.2 hours (about 8 days) in the group administered placebo. The results of examining how much viral RNA was reduced on the 4th day of administration also showed that the Ensitrelvir administration group decreased significantly compared to placebo.
Xocova is designed to block the activity of 3CL protease, a key enzyme needed when the COVID-19 virus (SARS-CoV-2) proliferates in cells. The mechanism is similar to Xocova and Paxlovid, but there is a large difference in clinical design. In the case of Paxlovid, the risk of hospitalization and death decreased by 89% as of the 28th day of administration. As of the 29th day of administration, Lagevrio's risk of hospitalization and death decreased by 30%. There is also a result that additional clinical trials conducted in India and other countries showed 65% effect. Xocova is expected to be less burdened by taking drugs than Paxlovid and Lagevrio.
Paxlovid and Lagevrio have many drugs to take at once. Paxlovid is taken twice a day for a total of 5 days as a set of Nirmatrelvir and Litonavir. The total number of pills to be taken for five days is 30. 4 capsules of Lagevrio is taken twice a day for 5 days. The total number of pills taken during the treatment period amounts to 40 capsules.
Xocova is taken once a day for a total of 5 days. The number of pills to be taken per episode has not been clearly determined, but it is known that three tablets are taken on the first day and one tablet is taken every day since then.
If Xocova is approved EUA in Korea, it will be the third drug for oral COVID-19. The Ministry of Food and Drug Safety conducted EUA on Paxlovid in December last year and Lagevrio in March this year.
In the case of Paxlovid, the EUA was decided five days after the request of the Korea Centers for Disease Control and Prevention (December 22, 2021). It is only 48 days, including the period of preliminary review by the Ministry of Food and Drug Safety. Lagevrio took a total of 127 days from the request of the Korea Centers for Disease Control and Prevention (November 17, 2021) to the EUA decision of the Ministry of Food and Drug Safety. Considering the previous cases, Xocova is also expected to take two to four months to make the EUA decision. However, the pharmaceutical industry's prospects are mixed as to whether the Ministry of Food and Drug Safety will finally decide Xocova's EUA.
A pharmaceutical industry official said, "When Japan withheld its judgment on EUA in July, we agreed to wait for phase 3 results to see more accurate data and make a final decision," adding, "We confirmed the effect of improving symptoms through large-scale clinical trials, so the possibility of EUA in Japan has increased. If the EUA is decided in Japan, it will also help the EUA in Korea, he predicted. Some predict that the EUA will be difficult considering the domestic COVID-19 epidemic.
Shionogi applied for Xocova's conditional permission to the Japanese Ministry of Health, Labor and Welfare in February this year. Since then, the EUA application bill in Japan has been passed, and in June and July, the Ministry of Health, Labor and Welfare and Food Sanitation Council discussed whether to do so. The Pharmaceutical Affairs Council mainly said, "It is effective in reducing the amount of the virus, but there is not enough data to improve clinical symptoms."
In Korea, Ildong Pharmaceutical plans to launch EUA regardless of Shionogi. In August, domestic clinical trials were completed. Ildong Pharmaceutical plans to apply for EUA in Korea by submitting the results of phase 3 clinical trials in Japan along with domestic clinical results.
- Research service for re-evaluation of listed drug benefits
- by Lee, Tak-Sun Sep 30, 2022 05:53am
- The HIRA will conduct a study on the re-evaluation of drug benefit adequacy with the aim of ending in February next year. Through this, it will be used as a policy to promote re-evaluation projects. The HIRA announced on the 27th that it would bid for a research service to rationalize the evaluation of drug benefit adequacy. Ticketing is scheduled to take place on October 5. The research period is four months from the date of signing the contract, and the goal is to end in February next year. The budget was allocated 60 million won.
The HIRA explained that through this study, it will come up with a reasonable target selection and evaluation standard improvement plan to stably establish a benefit adequacy re-evaluation system, operate an effective system, enhance predictability of stakeholders, and prevent unnecessary issues.
Re-evaluation of drug benefit adequacy is being conducted by the first comprehensive health insurance plan (2019-2023). Therefore, the relevant grounds will be lost next year.
This year, The HIRA has prepared criteria for selecting the grand prize, but there is no research to support this. In the first half of last year, the HIRA set the criteria for the long-standing registration year when selecting the subject for re-evaluation, and decided to evaluate the clinical usefulness first, considering cost-effectiveness and social demands if necessary.
This is why this study is necessary because the re-evaluation does not achieve the purpose of reducing insurance finances immediately. The HIRA is suspended from administrative litigation and execution by pharmaceutical companies in all three components and Choline alfoscerate in 2020. The committee pointed out that the achievement of the purpose of the system is insufficient and that the reduction of insurance finances is being delayed.
Accordingly, this study plans to conduct policy proposals for selecting targets for re-evaluation and improving evaluation criteria and methods through analysis of domestic and foreign reimbursed drugs, and adequacy re-evaluation system. The main contents of the study are policy suggestions for analyzing the current status and revaluation (post-management) system in Korea, analyzing the overseas revaluation (post-management) system and status, and re-evaluating the rational drug benefit appropriateness (spending efficiency). The HIRA expected that this service study will be used as a policy for selecting targets related to the promotion of drug benefit adequacy re-evaluation projects and managing reimbursed drugs.
- 1st KRAS drug Lumakras can be prescribed at general hospital
- by Eo, Yun-Ho Sep 29, 2022 05:50am
- Lumakras, the first targeted anticancer therapy to target the KRAS mutation, can now be prescribed at general hospitals in Korea.
According to industry sources, Lumakras (sotorasib), Amgen Korea’s treatment for locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations, passed the drug committees of the Big 5 tertiary hospitals in Korea including the Samsung Medical Center, Seoul National University Hospital, Seoul Asan Medical Center, and Sinchon Severance Hospital, as well as other medical institutions nationwide, such as the Gangnam Severance Hospital, Korea University Anam Hospital, National Cancer Center, Seoul National University Bundang Hospital, Chungnam National University Hospital, Kyungpook National University Chilgok Hospital, and Chonnam National University Hwasun Hospital.
Considering that the drug was approved in Korea in February and not listed for reimbursement yet, the drug is quickly settling in medical institutions in Korea. Amgen is currently preparing for its reimbursement in Korea.
Lumakras is approved for use as second-line or subsequent treatment in adult patients with KRAS G12C-mutated, locally advanced, or metastatic non-small cell lung cancer.
Lumakras is the first targeted therapy to be approved by the Ministry of Food and Drug Safety for KRAS G12C NSCLC patients. KRAS is one of the major oncogenes is found in various cancers including NSCLC and is present in 25% of all NSCLCs. It is the second-most common mutation that occurs in Asian patients after EGFR mutations.
NSCLC patients with the KRAS G12C mutation have shown a lower relative survival rate than other lung cancer patients in surgery or chemotherapy as many are resistant to existing standard therapies.
Lumakras is the first-ever oral treatment that selectively inhibits the KRAS G12C mutant protein that is involved with the development of lung cancer. It inactivates the KRAS G12C mutant protein that promotes tumor growth to effectively block the signaling oncogenic activity without affecting the wild-type KRAS.
Professor Myung Ju Ahn from the Samsung Medical Center said, “KRAS G12C-mutated NSCLC is an area where a dire need remained for a new treatment option. The domestic approval of Lumakras, the first targeted therapy for KRAS G12C mutated NSCLC, is news that both the patients and the field have been long awaiting for. Based on the excellent treatment effect and safety profile confirmed in clinical trials, Lumakras is expected greatly contribute to improving the prognosis of patients if introduced to the field.”
Meanwhile, the efficacy of Lumakras was demonstrated through the Phase II CodeBreaK100 trial that included 124 patients with KRAS G12C-mutated locally advanced or metastatic NSCLC.
Patients enrolled in the trial had all progressed after chemotherapy or immunotherapy. Results showed that the overall response rate (ORR) that includes both partial and complete responses was 36%. Also, 82.3% of the patients treated with Lumakras showed tumor shrinkage, with a media maximum tumor shrinkage of 60% in all responsive patients, showing a consistently high treatment effect.