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- 2025-12-24 10:00:02
- Policy
- Forxiga's pro-drug by Dong-A ST, conducted clinical trials
- by Lee, Tak-Sun Jul 14, 2020 06:11am
- Dong-A ST recently succeeded in overcoming a material patent, and SGLT-2 suppression-based diabetes treatment Forxiga by AstraZeneca is speeding up commercialization. IND has already been approved by the MFDS in April. According to the MFDS on the 10th, IND of Dong-A ST's 'DA-2811' was approved on April 16 to confirm its equivalence with Forxiga. According to the recently published plan, DA-2811 is tested with Forxiga 10 mg (Dapagliflozin), Comparator. and a clinical trial is conducted in 60 healthy adults in the month of July at Seoul National University Bundang Hospital. Clinical trials are conducted in a public, randomized, single dose, or cross-over manner to evaluate pharmacokinetic properties, safety, and tolerability compared to Forxiga. Dong-A ST's DA-2811 has no medicinal properties in itself, but when absorbed by the human body, it turns into an active ingredient and is known as a pro-drug. In a recent patent trial, Dong-A ST was the first domestic drug company to evade Forxiga's substance patent (expired on April 7, 2023) with this pro-drug. Accordingly, upon successful commercialization of the product, it laid the foundation for bringing the product to market. It is known that Forxiga's material patent specification does not include pro-drug in its scope of rights. Looking at the trial of the patent trial, Donga ST's product is a prodrug ester compound in the form of formic acid bound to the carbon at the glucose site in the Dapagliflozin molecule. It was named 'Dapagliflozin Formate' in the trial. In other words, when Dapagliflozin Formate is administered to the human body, Dapagliflozin is a drug that produces an active ingredient. Comparison of chemical formula between Forxiga (left, AZ) and prodrug (right, Dong-A ST) (Source: Patent trial decision)Because of this characteristic of the prodrug, securing the comparability with the original reference drug is interpreted as the key to commercialization. Animal model tests have been shown to demonstrate equivalence. Dong-A ST plans to successfully complete phase I clinical trials and apply for permission in the first half of next year. Dong-A ST, along with SGLT-2, possesses the DPP-4 inhibitor, Suganon, which is currently leading the diabetes treatment market, so it is likely that Forxiga's prodrug will be more competitive if it is released early.
- Policy
- NHIS expects avg 322 generic pricing negotiations per month
- by Lee, Hye-Kyung Jul 13, 2020 06:12am
- Korea’s National Health Insurance Service (NHIS) is to start negotiating with generics over healthcare reimbursement contracts from the second half of the year. At a press conference convened on July 7, NHIS Reimbursement Executive Director Kang Chung-hee stated, “For the pricing negotiation on generics to be conducted from August to September, the Drug Pricing System Improvement Division previously operated under one team of six staffs in one division would be expanded to two teams of nine staffs in one division.” According to the deliberations done by Health Insurance Policy Deliberation Committee (HIPDC) from last year January to last March, average 322 generic items would be negotiated for pricing every month. When NHIS initiates pricing negotiation with generic, pharmaceutical companies would have a preliminary consultation with NHIS regarding negotiation and contract compliance as they submit an application for reimbursement listing to Health Insurance Review and Assessment Service (HIRA). After HIRA calculates drug pricing, the pursuing company should engage in a pricing negotiation with NHIS for 60 days and a deliberation by HIPDC before the final announcement of listing and pricing is made. Director Kang said, “The negotiation process would be streamlined through preliminary consultation with pharmaceutical companies,” and “the contract would become the focal point of the generic supply and quality management.” For the process, NHIS held a meeting on July 8 with Korea Pharmaceutical and Bio-Pharma Manufacturers Association (KPBMA), Korea Biomedicine Industry Association (KoBIA) and Korean Research-based Pharmaceutical Industry Association (KRPIA). At the meeting, NHIS explained about detailed guidelines of revised ‘Regulations on National Health Insurance Reimbursement Criteria’ and ‘Pharmaceutical Decision and Adjustment Standards,’ which mandate a 60-day drug pricing negotiation on generics listed through authorized pricing calculation, instead of pricing negotiation. Answering the industry representatives’ concern on the pricing negotiation delaying the listing process, Director Kang said, “The Ministry of Health and Welfare would decide on the detailed guideline,” and “the delay would be minimized by conducting a preliminary consultation first.”
- Policy
- Clarifying the conditional approval target
- by Lee, Tak-Sun Jul 13, 2020 06:12am
- Chief Ho-sang Jeong (left) & team leader Jeong-won Oh (right), who conducted briefings with the reporters on the 7thThe MFDS strictly enforces the Advanced Bio Act (the Act on the “Safety and Support of Advanced Regenerative Medical and Advanced Biopharmaceuticals”), and said that concerns about safety are only a concern. However, the conditional approvals subject to the enacted legislation will maintain the previous conditions. Ho-sang Jeong, chief of the Cell Gene Therapy Products Division, and Jung-won Oh, leader of the permission team of the MFDS, who is in charge of the screening and licensing parts of the cell and gene therapy products, said in a press briefing on the 7th. On August 28, the MFDS issued an administrative notice by setting up 'Regulations for Permit and Examination of Items for Advanced Biologics' prior to the implementation of the Advanced Bio Act. Accordingly, advanced biopharmaceuticals such as cell therapies and gene therapies that have been applied to the existing the pharmaceutical affairs law will be subject to the new regulations within the framework of the new law. Although the number of licensed items for cell and gene therapies in Korea is small, it is a new kind of treatment, and there are many items developed by listed ventures, which is of interest. In addition, the necessity for strengthening the permit screening is being raised through the case of Invossa, a gene therapy product that has been canceled. Some are also raising concerns about whether drugs subject to expedited review or drugs subject to conditional approval, such as exemption of a phase III, will be screened with neglecting safety. In response, the MFDS explained that safety measures were faithfully reflected in the law to prevent safety problems. For example, a follow-up management system, such as a long-term follow-up survey, was established. ""In fact, even before the law was enforced in August, the screening system for cell and gene therapies was prepared similarly to the standards of developed countries," said Ho-sang Jeong. He said, "The Advanced Bio Act supports high-tech biopharmaceuticals while strengthening safety at the same time, and the rapid review regulations that existed at the public notice level have been enacted, so that the drugs subject to rapid review can be approved within a short period of time." In the meantime, "the criteria for rapid review or conditionally approved products have been clarified, so that there are no concerns about safety due to the misuse of conditionally licensed medicines at some point." He added, "The management became tighter while clarifying the measures for under-conditional items." The MFDS is also considering the input of screening personnel tailored to this. The conditional approval was mainly a system to conditionally phase III clinically and approve items in phase II completion. It was possible because there were no existing treatments, significant life-threatening diseases, or endpoints that could predict clinical benefit. However, these conditions were abstract, and there were few cases where conditionally approved drugs were actually used in patients. The MFDS recognized this problem and explained that the Advanced Bio Act clarified the requirements for conditional approval or expedited examination. Accordingly, it is expected that there will be fewer cases of disagreement over the conditional approvals with companies. The MFDS recently filed a lawsuit against Pharmicell for a conditional license for 'Cellgram-LC' and lost it. However, it is the policy that the conditional permits and pre-licensed items will maintain the previous conditions. The Advanced Bio Act states that licensed items must be re-applied within one year after promulgation. Accordingly, 16 items of cell therapy products must be re-applied. Some of these items are licensed under the condition of phase III. "The three items are conditionally approved under the premise of phase III clinical trials, and the items under phase III clinical trials are planned to maintain the existing license conditions until the re-application is made," said Jeong-won Oh. "On the 3rd, the information submitted to companies with re-permitted items was guided. Basically, safety and effectiveness data have similar requirements according to the pharmaceutical affairs law. They have to submit the data in CTD version," he explained.
- Policy
- Mixed responses on exempting PE for antibiotics
- by Eo, Yun-Ho Jul 10, 2020 06:14am
- The people are voicing both positive and negative reactions on the pharmacoeconomic evaluation (PE) exemption track opened to antibiotics. Considering the unique characteristic of the drug, expanding the coverage on antibiotics with the difficulty of conducting PE is an improvement. But there is a dispute brewing on the definition of antibiotics. In March, Korea’s Ministry of Health and Welfare (MOHW) and Health Insurance Review and Assessment Service (HIRA) preannounced the revised regulation of pharmaceutical healthcare reimbursement subject evaluation criteria and procedure, and started accepting relevant public opinion. The noticeable changes in the regulation related to PE exemption track is expanding the subject scope, currently limited to rare disease only, to include tuberculosis treatment, antibiotics, and emergency antidotes essential to promote public health. ◆A definition of antibiotics could cause confusion The controversial issue is in the definition of ‘antibiotics,’ which could get limited to ‘antibacterial.’ Apparently, the government has expressed intention to positively review the issue as raised by Korean Research-based Pharmaceutical Industry Association (KRPIA). As a medical term, antibiotics means ‘antimicrobial medicine’ functioning as ‘antibacterial (treating bacterial infection),’ ‘antifungal (treating fungal infection),’ and ‘antiviral (treating viral infection).’ And constant rise of antimicrobial resistance (AMR) has been addressed as the most alarming public health issue around the world. Usually, many people interchangeably use the term antibiotics as antibacterial or antimicrobial. But medically speaking, drugs used to impede growth of microbe, like bacteria, fungus and virus, are categorized as antimicrobial medicines. President Choi Jung Hyun (Infectious Disease Division of the Catholic University of Korea Eunpyeong St. Mary’s Hospital) of Korean Society for Antimicrobial Therapy (KSAT) said, “As PEs were conducted without full understanding of newly developed antibiotic and antifungal drugs targeting antibiotic-resistant bacteria, which cannot be treated with other existing options, the drugs were impossible to enter the Korean market. The sources of infectious diseases like bacteria, fungus and virus should be handled by taking in account of possible development of AMR during treatment. ◆The background of introducing PE exemption track on antibiotics The objective of revising the regulation is to revisit some of criteria in PE exemption track to include drugs, challenged to produce PE results but essential to public health improvement. The clinical trial on antibiotics tests non-inferiority against a reference drug. As antibiotics have to treat infectious disease, it is unethical to confirm superiority or to use a drug with developed AMR and diminished treatment effect as a reference drug to confirm superiority. Under such circumstances, PE has been pointed out as the cause of delay in listing antibiotics regardless of the high medical needs. The industry highly anticipates the revised PE exemption benefit would contribute in promptly and reliably supplying new antibiotic and antifungal drugs to Korean market. The U.S. Food and Drug Administration and the European Medicines Agency (EMA) also approve new antibacterial and antifungal drugs based on non-inferiority clinical trial results. President Choi stressed, “We would like to express our appreciation for the government’s effort to secure infectious disease treatment crucial in responding against severe infection seriously threatening the public health. The regulation revision would provide the foundation to have stable access to antibiotic and antifungal drugs to treat antibiotic-resistant bacteria. It would also be a great help for developing the antimicrobial stewardship and resistant bacteria practice guideline the academic society is leading.” Introduced in 2015, the PE exemption track, also known as ‘special PE benefit,’ excludes rare disease treatment or anticancer treatment from the PE data submission requirement, a part of pharmaceutical reimbursement review process. The drugs listed with PE exemption track are applied with expenditure cap type risk sharing agreement (RSA). However, the public has been constantly demanding for the PE exemption subject to expand as drug other than anticancer or rare disease treatment struggling to prove the cost-effectiveness. This marks the first revision made since the system was established in 2015.
- Policy
- Dongkuk's DKF-313 entered clinical trial phase III
- by Lee, Tak-Sun Jul 10, 2020 06:13am
- The prostate hyperplasia complex developed by DongKook Pharmaceutical enters Phase III clinical trials. YuYu Pharma is also developing the same prostate hyperplasia complex, which attracts interest in the competition between the two companies. On the 9th, the MFDS approved the clinical trial phase III trial (IND) for 'DKF-313', which DongKook Pharmaceutical applied for. DKF-313 is known as a combination of Dutasteride and Tadalafil currently used in prostatic hyperplasia. This trial is a multicentre, randomized, double-blind, double placebo, parallel group, phase III clinical trial to evaluate the efficacy and safety of DKF-313 in 654 patients with benign prostatic hyperplasia. The test will be conducted at Asan Medical Center. Dutasteride-Tadalafil combinations are currently not commercially available. It will be the first in the world If developed. YuYu Pharma was approved for a phase III clinical trial plan for 'YY-201,' a candidate for the same ingredient in March 2018. Therefore, it is noted who will succeed in commercialization first. The size of the domestic prostate hyperplasia treatment market is about ₩200 billion , and the original drugs of foreign pharmaceutical companies occupy most of the market share. Representative drugs include Harnal (Tamsulosin HCl, Astellas Korea), Avodart (Dutasteride, GSK), and Proscar (Finasteride, MSD). Tadalafil (Cialis, Lilly) is more famous for erectile dysfunction, but is also used for benign prostatic hyperplasia in low doses. For reference, Dutasteride is effective for prostate hyperplasia as well as hair loss. Therefore, if a combination drug is developed, it is expected that it will be spotlighted in patients with erectile dysfunction and hair loss accompanied by prostate hyperplasia. It seems to be the key to commercialization whether it is possible to increase the solubility of the two components in a single formulation in view of the fact that Dutasteride is a poorly soluble drug that is insoluble in water.
- Policy
- Safety verification data should be submitted for Metformin
- by Lee, Tak-Sun Jul 10, 2020 06:13am
- When applying for the approval of Metformin, a diabetes treatment drug for which carcinogenic substance NDMA has been detected, additional safety verification data should be submitted in the future. In particular, data that can prove that NDMA is not generated during the process should also be attached. According to the industry on the 8th, the Convergence Innovation Product Support Group of the MFDS recently prepared a 'Metformin Raw Material and Containment Authorization Management Plan', and provided information through associations. On May 26, the MFDS discontinued and recovered 31 items of Metformin in which NDMA, a carcinogenic substance, was detected excessively. It was instructed to submit process verification data demonstrating that NDMA is managed below the standard in the manufacturing process of the drug product by August 31st. The management plan prepared this time is about the permission, notification and registration (change) of raw materials and containing agents. According to the management plan, if new raw materials and containing agents are managed under NDMA management (maximum allowance of 96 ng per day), permission, notification and registration are processed. In addition, it is planned to check the evidence only for quality-related changes (raw drug and its quantity, manufacturing method, manufacturer, storage method, and usage period). Safety data includes 'process verification data' that can prove that NDMA is not generated during the process, and 'stability data' that has undergone long-term preservation tests. Specifically, the process verification data includes process variables that may affect NDMA production, NDMA generation potential review data due to the effect between Metformin and other components, storage conditions tests, and packaging and container reviews, In the future, NDMA occurrence in the manufacturing process or preventive/corrective measures that can be adjusted within the maximum allowable capacity per day, and NDMA detection variability between manufacturing lot numbers are considered. It also includes considerations for NDMA test results and test method validation data (when using its own test method), manufacturing process, process inspection, and standards. The stability data is based on the new drug, and the period of use is set by the long-term preservation test, but the period of use is set within 24 months based on the long-term preservation test for 12 months, the accelerated test for 6 months. NDMA detection list is added to the stability test, and in the case of the test method, validation data is exempted when using the test method by domestic and foreign regulatory agencies such as the MFDS. However, at least one actual production batch data should be submitted when selecting a stability test lot. The MFDS plans to supplement and submit safety proof data in connection with the process of complaint handling in the case of permits, reports, and changes to Metformin.
- Policy
- Government asks Gilead to import Remdesivir for 5,360 people
- by Lee, Jeong-Hwan Jul 10, 2020 06:13am
- While COVID-19 Pandemic was prolonged, it was found that the government limited the amount of Remdesivir, which was known to be effective in COVID-19 treatment, to 5,360 servings. The Central Disease Control Headquarters requested an emergency import of Remdesivir for 360 people and the pandemic preparation for 5,000 people. Kang Giyun, a member of United Future Party said on the 8th, "As a result of confirming the private internal documents of the KCDC, only requested the import of Remdesibir for 5,360 people." An antiviral drug, Remdesibir, was approved by the US FDA on May 1st for emergency use following the announcement that the recovery period for COVID-19 inpatients has been reduced by 31%. Currently, the United States has announced plans to secure 92% of Gilead's production of Remdesibir by the end of September. It means that countries around the world have jumped into the battle to secure the quantity of Remdesibir, and the competition has become fierce. Provided by Kang Ki-yoon In this situation, the KCDC asked Gilead Korea on the 3rd of last month to import Remdesibir for 5,360 people. According to data released by Kang Giyun, the KCDC officially sent Gilead a request of Remdesivir for urgent use (for 360 people) and the pandemic (for 5,000 people). Earlier, the KCDC received a portion of the free supply from Gilead in July and supplied Remdesivir to 29 domestic patients as of July 6th. Some of the quantities supplied by the KCDC in July have not been revealed, and the company plans to continue to purchase Remdesivir through price negotiations with the goal of importing 5,360 people from August. A member Kang said that the U.S. government is swearing that all Americans will get treatment whenever they want, and it is not possible to specify when the pandemic will end and when a domestic outbreak will occur. Also he added that it is necessary to properly check whether the amount of 5,360 servings is appropriate in terms of scale and secure sufficient treatment.
- Policy
- Hanmi loses out on patent trial, drops Vildagle approval
- by Lee, Tak-Sun Jul 09, 2020 06:26am
- Hanmi Pharmaceutical dropped the sales approval on antidiabetic dipeptidyl peptidase-4 (DDP-4) inhibitor Vildagle 50 mg tablet (vildagliptin hydrochloride) that the company won by excluding the indication relevant to Galvus’ extended patent. Sources interpret the Korean company’s action was following up with the failed attempt to evade the original drug Galvus’ patent at a patent trial earlier this month against Novartis Korea. According to Korea’s Ministry of Food and Drug Safety (MFDS), Hanmi Pharmaceutical’s withdrawal of the sales approval on Vildagle 50 mg tablet was decided as of July 6. The product received the health authority’s item approval on Jan. 21 and even received reimbursed pricing in last April as well. The drug was initially targeting an early release to the market by applying for the approval without indication based on the original Galvus’ extended patent, which is to last until Mar. 4, 2022. However, the product was not yet released as the patent evasion was not fully approved during the legal proceedings. On July 1, Intellectual Property Trial and Appeal Board rejected Hanmi Pharmaceutical’s request to confirm the negative scope of the original’s patent. Without the complete patent evasion, the product would be able to enter the market only after Mar. 4, 2022 when the original patent term expires. The Korean company could have judged it would be better to reapply for the approval with all indications identical to Galvus. The company has already succeeded in shortening the extended original patent term through the Intellectual Property Trial and Appeal Board, and is ready to launch the product from Aug. 30, 2021. But Ahn-gook Pharmaceutical is also launching its vildagliptin drug from then. As Hanmi Pharmaceutical withdrew the approval, there is no need for Novartis to continue on with the litigation proceedings against MFDS to revoke Hanmi Pharmaceutical’s approval. Novartis has filed litigation against MFDS claiming the government body has neglected its duty to notify the patent owner, according to the Patent-Approval Linkage System, when Vildagle applied for an approval. Now that Hanmi Pharmaceutical has retracted its early release scheme, other pharmaceutical companies also targeting for an early release would inevitably have to revisit the strategy on approval application and challenging the original patent.
- Policy
- The Korean New Deal was confirmed by supplementary budget
- by Kim, Jung-Ju Jul 09, 2020 06:26am
- During the COVID-19 situation, supplementary budget of ₩1.088 trillion was established to strengthen the MOHW for the so-called 'Korean New Deal' project. At the plenary session of the National Assembly on the night of the 3rd, the MOHW focused on ▲strengthening K-disinfection capabilities and R&D investment, ▲ establishing a non-face-to-face basis (infrastructure) for infectious diseases, and ▲expanding the Korean jobs and social safety nets. The government announced that it had increased by ₩34.6 billion compared to the government proposal (₩1.054 trillion). The increase was ₩22.4 billion for the National Immunization Program for influenza targeted at ages 62-64, ▲ ₩12 billion for supporting medical personnel such as COVID-19, ▲ ₩200 million for the establishment of an integrated information system for epidemiological investigations of infectious diseases. ◆Strengthening K-disinfection capabilities and R&D investment =₩48.9 billion was set for the expansion of national immunizations (45.5 million people) for 14~18, 62~64 yearolds in preparation for the possibility of COVID-19 in the future and ₩200.9 billion was set for quarantine items such as level D protective clothing and masks. ₩10.2 billion established for the construction of negative pressure screening clinics in the 67 public health centers in order to expedite medical treatment at local areas, Following the first supplementary ₩400 billion in medical institutions with a sharp drop in sales due to COVID-19, additional ₩400 billion in financing was also established. COVID-19 treatment and vaccine support for clinical trials, advancement of quarantine equipment, and expansion of research and development (R&D) related to the expansion of the infrastructure of the National Institute of Virus and Infectious Diseases will be able to invest ₩140.4 billion. ◆The Korean New Deal project = 5G network, monitoring equipment, etc., including the establishment of non-face-to-face infrastructure for infectious diseases, increased ₩6 billion to minimize the risk of infection in hospitals and establish smart hospitals (3 locations) for efficient treatment. In order to prepare a safe medical treatment system for patients with respiratory diseases and prepare for the possibility of secondary epidemics, ₩50 billion was set up to establish a dedicated respiratory clinic (500 locations), and ₩1.1 billion was confirmed to expand health management projects (130→140 locations) through local clinics and public health centers using ICT devices. ◆Expansion of jobs and social safety netwrok =₩58.3 billion for temporary job support (6,312 people) to provide quarantine support for health centers and hospital-level medical institutions, and extended periods for relief of urgent welfare support requirements (July → end of the year) to expand support for low-income households threatened with livelihood According to the supplementary budget, the total spending by the MOHW in 2020 increased from ₩86.165 trillion to ₩87.146 trillion. Projects that are difficult to execute with COVID-19 will be used as additional financial resources by reducing ₩107.7 billion through restructuring expenses. The MOHW announced that it would thoroughly prepare for the rapid execution of the supplementary budget, and will actively strive to protect people's safety from COVID-19 and support public economy.
- Policy
- 13 drugs were sold before patent termination
- by Lee, Tak-Sun Jul 08, 2020 05:37am
- Domestic pharmaceutical companies were caught largely on charges of sales before patent termination. These pharmaceutical companies reported to the MFDS that they would sell after the end of the patent at the time of the application, but the sale was made even before the end of the patent through reporting on supply. The industry believes that they have committed illegal acts due to a lack of understanding of patent-linkage system introduced in 2012. However, there are criticisms that pharmaceutical companies have responded too easily because the allegations of selling before the end of the patent are just the reason for canceling the license. The MFDS has recently disclosed the results of disposing of products suspected of being sold prior to the termination of the patent. A total of 13 items were revoked by the 5th. These items are generic (Varenicline) for Pfizer's anti-smoking treatment 'Champix', and generic (Bazedoxifene Acetate) for Pfizer's osteoporosis treatment 'Viviant'. It was discovered that the items for cancellation of license were sold before the patent expired. According to the Pharmaceutical Affairs Act, the drug is withdrawn before the period expires if a person who applied for approval or revised approval of a drug is filed to market the drug after the period of a registered patent expires. This was reflected in the Pharmaceutical Affairs Act at the time of the introduction of the licensed patent linkage system in 2012. In the case of generic drugs with original patent rights, the application for permission is accompanied by a confirmation of the relationship of the patent, which is to be sold before patent termination through patent challenge or after patent termination. This is notified to the patent holder so that the patent holder can prepare in advance. A patent owner may make a request for prohibition of sales for nine months with a lawsuit against an item deemed to be infringement of a patent to the MFDS. Although the item that was caught this time has been applied for permission to be sold after the patent is over, it is suspected of being sold even before the patent expires. It is known that the MFDS caught the items sold before the end of the patent through report on supply history and field investigation. Administrative measures are underway because more items are caught than the 13 items that have been released so far. According to the industry, hepatitis B treatment and erectile dysfunction treatment are also included. It is known that some companies have additionally approved salt-altering items in preparation for cancellation of the license or have obtained the same active ingredients through affiliates.
