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- 2025-12-19 22:26:23
- Opinion
- [Reporter’s View] No innovation without failure
- by Son, Hyung-Min Jul 01, 2024 05:47am
- Korean biopharmaceutical companies are exchanging joy and sorrow over out-licensing agreements. Last month, three companies, including HK inno.N, have successfully signed agreements to out-licensing of their new drug candidates in addition to AprilBio and ISU Abxis. In contrast, there are instances where new drug candidates that have been successfully out-licensing are later returned. GC Cell announced that a collaborative R&D agreement with Artiva Biotherapeutic, its U.S. subsidiary, for three treatments for CAR-NK solid tumors in 2021 has terminated. Furthermore, Olix Pharmaceuticals and Curacle received notifications of contract terminations from France’s Thea Open Innovation last month. In April, Voronoi terminated the out-licensing agreement made in 2022 with METiS Therapeutics, a biotech company in the United States, for its solid tumor treatment VRN14. Yet, it is too early to be disappointed about the termination of out-licensing agreements. There are instances where companies can succeed by developing drugs for new indications. For instance, last year, Hanmi Pharmaceutical confirmed the potential of Poseltinib for the treatment for recurrent or diffuse large B-cell lymphoma (DLBCL). The licensing of Poseltinib, a BTK inhibitor under development by Hanmi Pharmaceutical, was returned from Lily in January 2019 because the efficacy of the drug was not confirmed in a phase 2 trial involving patients with rheumatoid arthritis. Additionally, Hanmi Pharmaceutical is showing a process in clinical trials for efpeglenatide, a new drug candidate for obesity. Efpeglenatide is a product that initially struck a licensing agreement with Sanofi in 2015 to treat diabetes and later returned to Hanmi Pharmaceutical. Then, Hanmi Pharmaceutical changed its development strategy for this drug to a Korean-focused obesity treatment. Based on recent clinical results, Efpeglenatide demonstrated weight loss effects. During the new drug development process, selecting and focusing are necessary steps. The company’s R&D strategy can be changed, and instances of new drug candidates that fail to demonstrate efficacy can occur. Out-licensing returns are common practice in the pharmaceutical industry. Fortunately, none of the four returned new drug candidates had significant issues regarding their efficacy. Companies with returned technologies plan to proceed with later phases of clinical trials without delays. Now is the time for companies to clearly announce their potential development directions to seek future investment opportunities. When clear directions are suggested, they could seek opportunities to out-license their new drug candidates again. There is no innovation without failure. If a company firmly believes in a pipeline item (new drug candidate), it may not worry about each case of returned licensing or the success of out-licensing. Only the companies that are not discouraged or give up are poised to survive.
- Opinion
- [Reporter's View] No more exemptions, just deferrals
- by Eo, Yun-Ho Jun 24, 2024 05:47am
- The Korean government has set out to fix the pharmacoeconomic evaluation exemption system. Although the authorities coined it as an “improvement,” the direction seems to be near a “reduction.” A report on a study commissioned by the Health Insurance Review and Assessment Service was released at the end of last year. The study, titled 'Study on Preparing a Plan to Improve the System for Exemption from Submission of Pharmacoeconomic Evaluation Data,' analyzed the current status and issues of Korea’s pharmacoeconomic evaluation exemption system, which was introduced in 2015, and proposed measures for its improvement. The report claims that the core of the improvement plan is to change the exemption system into a deferral system. The report pointed out that the core of the positive-listing system is the cost-effectiveness evaluation, therefore, Korea should not exempt drugs from evaluations when other countries do conduct evaluations. Based on the research results, HIRA proposed a revision of the current PE exemption system. To this end, the HIRA and the Korean Research-based Pharmaceutical Industry Association (KRPIA) recently held their first meeting. The industry's reaction to this is understandably grim. The PE Exemption System is literally the only way out for drugs that are difficult to evaluate but deemed necessary. It contains various financial control devices and has embraced an "expenditure cap" design since its inception. In fact, the industry has been constantly claiming that the current system has too high a threshold and has consistently emphasized the need for its expansion. Of course, the contents of the recent report will not be reflected 100%. However, the proposed measures in the report will hardly be satisfactory for the industry. Even now, it is not easy for companies to apply for the PE exemption system, and the number of eligible drugs will be significantly reduced if the reform is implemented. For example, contrary to how the current 200 patients or fewer (the usual threshold required to be eligible for the PE exemption) requirement refers to the number of patients that fall within the drug's scope of use, the proposed reforms refer to a stand-alone disease, meaning that a drug that would have been eligible if it met the 200 patients or fewer requirement based on its genotype or line of therapy indication must now have 200 or fewer patients affected by the disease itself. The fundamental purpose of deferring the PE exemption is more difficult to understand. The pharmaceutical industry has constantly requested the application of a flexible ICER threshold. And we have heard endlessly about how Korea’s ICER threshold is too strict for drugs to be reimbursed. It is doubtful whether drugs that would not have been listed if not for the PE exemption system will be able to remain reimbursed when evaluated after the deferred period. If some regulations are tightened, some need to be loosened as well. The government is already planning to save national health insurance finances by implementing bold drug price reduction mechanisms such as external reference pricing reevaluations and revision of the price-volume linkage system. It may be that the number of applicable drugs has increased since the implementation of the system, rendering improvements necessary. However, it is also true that this system has served as a 'breathing hole' in Korea's listing system, we need to devise other ways out before closing that hole.
- Opinion
- [Reporter’s View] Reliability Verification Review Committee
- by Lee, Hye-Kyung Jun 20, 2024 05:48am
- The Ministry of Food and Drug Safety has formed a Reliability Verification Review Committee. In the 'Guideline for Drug Manufacturing, Sales, and Import Marketing Authorizations and Labeling Change Authorizations,' which was revised by the MFDS on the 17th, a procedure was added for the Reliability Verification Review Committee to verify the reliability of the permit data submitted by companies during the drug approval and review process. In the past, if data with questionable reliability was submitted during the approval and review process, nothing happened if the applicant withdrew the data. Unreliable data is data that is false or falsely presented data. In other words, if false data was submitted intentionally or unintentionally and detected, it was possible for the applicant to just withdraw the application in a ‘no harm no foul’ sense. However, in the future, the data submitted to MFDS will not be nullified even if the company 'voluntarily withdraws’ or 'voluntarily cancels’ the data. The reliability of all the data submitted will be verified without exception. If the committee determines that the submitted data is not credible, it will notify the headquarters and the follow-up department to initiate pharmacovigilance. This process will be applied to all data that are currently under review, even before the committee is formed. What should not be overlooked is that a suspicion of the reliability of an item in the approval/review stage can taint the reliability of the entire drug manufacturing plant during pharmacovigilance. The MFDS said that if the reliability of a single data in the early stages of review is questioned, it is possible to suspect "falsehood" and "falsity" of the entire manufacturing process. Therefore, if data submitted during the approval/examination stage is even slightly wrong, whether intentionally or unintentionally, this one issue can lead to 'revocation of the GMP certificate’ in the pharmacovigilance process. The MFDS also said that it "cannot be said that it is irrelevant" that the "questionable data" submitted by companies that do not follow the principle of good faith may be subject to future disposals up to the revocation of their GMP certificate. Although it may seem like just the MFDS reorganizing, launching a new committee, and refining its procedures, the launch of the Reliability Verification Review Committee seems to be one of those serious regulations that can even lead to the revocation of GMP certificate.
- Opinion
- [Reporter’s View] Finances limit reimbursement of drugs
- by Eo, Yun-Ho Jun 07, 2024 05:51am
- Insurance reimbursement standards and indications for a drug can differ. This is because the government’s pockets are not infinite under the National Health Insurance System. This is why there are always complaints in the field. Not all complaints can be resolved but there are some that evidently require resolution, that were made for incomprehensible “financial” reasons that are difficult to understand. Restrictions on age, duration, and switching drugs are typical examples. In the case of the age restriction, the standard is simple. For the same condition, infants, young children, or elderly patients may be excluded from coverage, or only certain age groups may be included due to concern about financial exhaustion. In this case, reimbursement is often extended later through reimbursement expansion measures. However, some drugs remain inaccessible for the patients. Restrictions set on the duration of use are a little different. Generally, reimbursement standards limit a drug's dosing interval based on the drug's clinical studies or authoritative international guidelines. However, there are also cases where reimbursement is restricted for "financial" reasons without any specific grounds for limiting the dosing interval. Restrictions on switching are the most frequent. Autoimmune diseases are the next big thing in the pharmaceutical industry after anticancer drugs, and numerous classes of drugs and same-class drugs with the same mechanism of action compete in the market. In the case of these drugs, the government often does not allow patients to be reimbursed for the first drug if they switch to another, meaning that if a patient is given a new drug with the expectation that it will work better than the first drug, but experience worse prognosis, he or she cannot go back to the old drug. The same situation was applied to drugs that were introduced long ago, and it took a long time before switching was granted reimbursement. In Korea, drug reimbursement has a significant impact on prescribing practices. Even if a patient needs a drug, doctors will often refuse to prescribe it if it is not reimbursed. This is why restrictions for financial reasons can be detrimental in fields where prescribing is essential. We ask the health authorities to trust the field’s judgment a little more.
- Opinion
- [Reporter's View] Expectations for new Alzheimer's drugs
- by Son, Hyung-Min Jun 05, 2024 05:47am
- Last month, a new drug for Alzheimer's disease, Leqembi, was approved in Korea. Leqembi, which was developed by Eisai and Biogen, targets the amyloid beta (Aβ) protein in the brain, which is considered one of the most likely causes of Alzheimer's disease. The industry welcomed Leqembi’s arrival because there had been no promising new drugs to treat Alzheimer's disease until now. Until now, donepezil, galantamine, rivastigmine, and memantine were used for Alzheimer's, but all were only able to relieve symptoms such as cognitive impairment and do not fundamentally treat dementia. Since then, a number of brain function improvement drugs have been introduced to prevent Alzheimer's disease but failed to prove their effectiveness. In 2022, acetyl-L-carnitine, which was used as a brain function enhancer, failed to prove its efficacy during clinical reevaluations, which led to its indication being removed. Oxiracetam also failed to prove its efficacy during clinical reevaluations last year and was removed from the market. Choline alfoscerate formulations also remain mired in controversy. The reason for the market exit of these drugs that had been used to improve brain function is lack of efficacy. The main problem with these drugs is that they have a jagged effect, which means that they may or may not improve the patient’s condition, depending on how the patient is feeling that day. Side effects have also slowed the development of Alzheimer's disease treatments. Alzheimer's is one of the leading causes of dementia, and it is believed that abnormal proteins such as amyloid beta protein and tau protein build up in the brain, causing nerve cells to die slowly. However, in the case of amyloid-targeted therapies, amyloid-related imaging abnormalities(ARIA), which are abnormal signals such as brain edema or microhemorrhage observed on MRI scans, may occur with their use. Aduhelm, which came close to commercialization before Leqembi also failed due to high rates of side effects in addition to its lack of efficacy. The good news is that other treatments have emerged that have shown promise in early Alzheimer's disease, including Leqembi and Lilly's donanemab. Both treatments target the amyloid beta protein, which is responsible for the development of dementia, and have shown efficacy in clinical trials with manageable side effects. In clinical trials, Leqembi improved a composite measure of cognitive function. This allowed patients with mild cognitive impairment to return to daily life to conduct day-to-day activities. Just as it is meaningful to extend the number of survival days of cancer patients by administering chemotherapy drugs, administering Leqembi is expected to have a similar effect. As we severely lack treatment options for Alzheimer's disease, new drugs are needed to expand treatment opportunities for patients. After the history of failures recorded in the development of Alzheimer's disease treatments, it would be interesting to see if the new Alzheimer's drugs can reverse the fate. It is the reporter’s hope the new drugs will be able to address the dire unmet needs of Alzheimer's patients in Korea.
- Opinion
- [Reporter’s View] An open talk on improving the GMP system
- by Lee, Hye-Kyung Jun 05, 2024 05:47am
- Last month, CEOs of biopharmaceutical companies submitted a statement to the Ministry of Food and Drug Safety (MFDS) requesting an improvement to the 'Cancellation of the GMP compliance decision (GMP One strike-out).' They asked that if non-compliance with GMP has been unintentional, a different set of measures be applied instead of one strike-out. On December 11, 2022, the MFDS initiated a GMP One strike-out act. According to this act, when a company is found to be in violation of the Good Manufacturing Practices (GMP) for medicinal products, their GMP compliance approval may be revoked. This measure has been established due to past incidents in which more than ten companies, including Binex, Vivozon Pharmaceutical, Hanall Biopharma, Dongindang Pharmaceutical, Hansol Pharm, Samsung Pharm, and Medica Korea, altered ingredients without authorization, falsified documents, and provided false information on approval documents. The GMP One strike-out act states that if a company violates GMP compliance, such as obtaining GMP compliance decisions based on false information or illegally and repeatedly falsifying GMP records, action will be taken. This year, there was a case of canceling the GMP compliance decision, and some items will soon be withdrawn. When a company receives a GMP One strike-out, manufacturing the offended item and the same formulation will be stopped. The system was implemented one year and six months ago. During this period, Hutecs Korea Pharmaceutical received a disposition and is pursuing a trial. The companies expecting a disposition may not readily accept the MFDS’s disposition. Consequently, there should be an opportunity to hear the opinions of biopharmaceutical companies CEOs regarding their statement for revising the GMP One-strike out system. The MFDS has reviewed the CEO’s statement regarding the GMP One-strike out system. However, the MFDS has not publicly discussed this matter or announced its official opinion. The MFDS may open a session with the CEOs if the Korea Pharmaceutical and Bio-Pharma Manufacturers Association (KPBMA), which represents biopharmaceutical companies in South Korea, officially submits a statement. However, the MFDS prefers to discuss this matter unofficially. The GMP One-strike out system has been implemented as part of revising the Pharmaceutical Affairs Act Article 38-2 (Standards of Manufacture and quality control). Since this system was established by the National Assembly, the MFDS, an administrative agency, feels certain pressure to discuss measures for revision. However, this policy has been implemented over one year and six months ago. There is a need to conduct a public review of the system. If the KPBMA proposes a clear agenda regarding this system, the MFDS official should provide an opportunity for official discussion.
- Opinion
- [Reporter’s View] We don’t know the fate of rivoceranib
- by Kim, Jin-Gu May 30, 2024 05:50am
- On the 17th, The US Food and Drug Administration issued a complete response letter (CRL) for HLB and Chinese Jiangsu Hengrui Pharmaceuticals’ frontline camrelizumab plus rivoceranib as a treatment for those with unresectable or metastatic hepatocellular carcinoma (HCC). Immediately after the news broke, HLB's stock price plummeted. The stock price, which was KRW 95,800, hit the floor for two days in a row, halving to KRW 47,000. Its market cap evaporated by more than KRW 630 billion in 2 days. As investors had high expectations for the company, which once recorded the second-largest market cap on KOSDAQ, the disappointment was as great. However, its stock has since rebounded, especially on the 27th and 28th, rising by more than 10% for two consecutive days and recovering to the KRW 63,500 level. The analysis is that HLB's strong claim that the FDA's approval was only delayed due to the facility issue at Jiangsu Hengrui Pharmaceuticals and that there is no problem with its final approval, has brought back the investors' attention again. Interpretations of the companies’ CRL receipt had been mixed. Some have said that the FDA "denied" the approval or that the companies have "failed," while others say the approval was just "delayed" or "pending. There is no special meaning to a CRL. It doesn't mean that the possibility of an FDA approval is long gone or that your approval is assured. Receipt of a CRL literally means that the FDA has requested a supplement to the application. Of course, as HLB claims, many new drugs have crossed the FDA threshold after receiving a CRL. HLB and Jiangsu Hengrui Pharmaceuticals plan to reapply for the FDA’s approval. They plan to resolve the facility issues that were pointed out as the reason for the CRL and try again. The exact time of the reattempt was not disclosed, but the industry expects the companies to reapply 'soon.’ We cannot predict whether the reattempt will end a success or failure. While many factors favor a positive outcome, there are also clear factors that point to a negative outcome. According to HLB claims, the CRL was unrelated to the efficacy and safety of the combination therapy. If so, this means that the combination therapy’s longest overall survival (OS) data compared to competing drugs is acceptable. In this case, the reapplication would only need to address the Jiangsu Hengrui Pharmaceuticals’ facility issues that caused the CRL. However, it is different if there are other causes besides the facility issue. In the past, the pharmaceutical industry has criticized the camrelizumab plus rivoceranib combination trial for not being double-blinded and for having a disproportionately large number of Asian patients. There are also other variables beyond the clinical and facility issues. One risk is that the US has been slow to approve new drugs from China for political reasons. The US recently passed the Biosecure Act, which actively restricts activity by Chinese pharmaceutical companies. Furthermore, the imminent release of clinical data of a potential competitor, the Opdivo plus Yervoy combination as a first-line treatment for liver cancer, also renders it difficult to be optimistic about the outcome. HLB Chairman Yang Gon Jin called the CRL a "double hit" for the company. However, it's too early to assess whether it's a double or a triple hit based solely on the FDA’s rejection or delay of approval. The ball hit by the HLB is still in flight. At this point, the ball could go over the fence or be out. Even if the FDA approves the product, the approval by itself would be hard to call a success. While it's clear that crossing the FDA's threshold is very difficult, it shouldn't be the ultimate goal. It’s as important to have a vision of how to commercialize the product after approval. So from various aspects, it is clear that it is too early to call rivoceranib a success or a failure, just based on the receipt of the CRL.
- Opinion
- [Reporter’s View] Lung cancer but also a 'rare disease'
- by Eo, Yun-Ho May 27, 2024 05:48am
- What appears to be the same 'cancer' type can be classified based on different numbers. Cutting-edge, targeted anticancer therapies are being developed to target an extremely small number of patients within a specific category of cancer. The cancer types we refer to as liver cancer, gastric cancer, and lung cancer are major categories, and they are classified as different subtypes. Even if a tumor originates from the same organ, treatment difficulty and the number of patients differ among these subtypes. The transition of medicine’s prescription criteria to the focus on 'genetics' is expected as precision medicine is already being developed. It is knocking on our door, yet we still need time to acclimate. These cutting-edge, targeted anticancer therapies can be used once patients’ genetic mutations are confirmed. However, the South Korean system is having difficulty accepting this type of therapy. Let’s examine the cases of lung cancer, which many anticancer therapies currently target. Anticancer therapies, such as RET-targeted medicines 'Gavreto (pralsetinib)' and 'Retevmo (selpercatinib),' MET-targeted medicines 'Tabrecta (capmatinib),' 'Tepmeko (tepotinib),' and 'Rybrevant (amivantamab),' attempted for reimbursement listing in the past years but they all failed. Although these anticancer therapies fall under the top category of 'lung cancer,' their subject category falls under for the number of patients with orphan drugs. Furthermore, previously listed targeted anticancer therapy and immunotherapy for cancer face hurdles in expanding reimbursement coverage. These drugs need value re-evaluation and prediction of the usage volume because the prices and the expanded usage are high. Such strictness is required to maintain the National Health Insurance system of South Korea. We cannot simply blame the government authorities. However, a transition of approach seems necessary considering one of the characteristics of recently developed novel drugs is that the number of patients, in other words, the number of mutations of a certain genetic, is quite few. As mentioned earlier, novel drugs only target a few patients. Out of the total solid cancer population in South Korea, less than 1% of patients have such rare disease, and less than 200 patients are diagnosed. Furthermore, the experts explain that these patients do not respond well to conventional therapies (previously used medicines). Because of these reasons, the industry has lately advocated for re-establishing the definition of a rare disease. The disease should reflect the number of patients per treatment option rather than the number of patients for the entire disease. Of course, such changes may require more detailed discussion. It’s time to put together ideas on how to have targeted anticancer therapies, which have expanded usage but are targeting fewer patients, to be covered by reimbursement. It’s true that there is an increased number of 'medicines available in the market but cannot be used' in South Korea. Now, the pharmaceutical companies need to be resolute, and the government needs to act.
- Opinion
- [Reporter’s View] Drug Review Coordination Council
- by Kim, Jin-Gu May 16, 2024 05:48am
- The Ministry of Food and Drug Safety (MFDS) has launched the Drug Approval and Review Coordination Council. The council will directly receive coordination requests from complainants when matters for supplemental measures arise during the drug approval and review process. With the Director-General of the Drug Safety Division heading the council, director-level officers at MFDS and 4-5 external experts will be coordinating the issues at hand. In other words, the council will coordinate issues that the MFDS has requested supplementation for under the leadership of the Director-General of the Drug Safety Division. Although it is a 1-year pilot program, the pharmaceutical industry has high expectations. This is because a significant portion of the pharmaceutical industry's complaints related to approval and review arose during the process of handling the supplementary measures. There always has been a discrepancy between the data requested by the MFDS and the data submitted by the pharmaceutical companies, and the process of closing the gap has always been fraught with complaints. The pharmaceutical industry was constantly thirsty for communication in this area. As the MFDS voluntarily offered to meet this need in this situation, the pharmaceutical industry welcomed the decision with open arms. In particular, the industry expressed expectations over the fact that the coordination process will be handled by the Director-General of the Drug Safety Division. The industry’s hope is that the complaints, which had become an ongoing hassle between working-level staff members of the MFDS and companies, will be adjusted more flexibly from a larger direction. However, no system, no matter how good, can satisfy 100% of the complainants who have expressed concerns over MFDS’s plan. The biggest concern is that the approval and review period could increase. With so many complaints focused on the processing of supplemental measures, the fear is that handling a large number of coordination complaints with limited manpower will create a kind of bottleneck phenomenon, increasing the time required for approval and review. As if acknowledging these concerns, the MFDS announced that it will exclude complaints for which there are clear regulations or have already gone through Central Pharmaceutical Affairs Council review. Furthermore, the MFDS is also planning to limit the number of coordination applications to '1 case per product by company'. Some in the industry are disappointed with this decision regarding the restriction. There were also concerns about equity. As the criteria for determining the coordination subjects is not clearly laid out, there is a possibility that complaints may arise on how the MFDs are only responding to the needs of certain pharmaceutical companies. The MFDS’s decision to open up a communication channel that the pharmaceutical industry has long awaited for is great news. Some industry insiders have complimented that the “MFDS has changed for the better.” However, this is the crucial moment. In order for the acclaimed MFDS’s plan to avoid becoming a ‘nothingburger,’ the authorities now need to prepare substantive sub-regulations, such as criteria for selecting coordination subjects, coordination procedures, and on how to apply the coordinated results.
- Opinion
- [Reporter’s View] MFDS’ Regulatory Innovation 3.0
- by Lee, Hye-Kyung May 14, 2024 05:48am
- The Ministry of Food and Drug Safety (MFDS)’s announcement of the regulatory innovation tasks is now an annual event. The Regulatory Innovation 1.0, announced just two months after Oh Yu-kyoung’s appointment as the minister, focused on regulations that need system improvements. Since 1.0 was criticized for not considering citizens’ opinions, 2.0 announced tasks, including managing digital safety, increasing consumer and small business benefits, and supporting future businesses. What about the implementation rate? The Regulatory Innovation 1.0, which included 100 tasks in three fields as part of the 'Improvement of Safety and Enhancement of Convenience for Health Functional Food,' had 88% implementation rate. 'Regulatory Innovation 2.0 Tasks for Food and Drug' solved 65 out of 80 tasks in five fields, showing 81.3% implementation rate. Both projects achieved over 80% implementation rate in a year. On May 2, the Regulatory Innovation 3.0 was announced. Unlike previous regulatory innovation announcements that felt like a mandatory annual event, 3.0 was different. Previous announcements lacked innovative tasks related to pharmaceuticals despite their intentions to include both food and drugs. While 1.0 and 2.0 merely updated old regulations, 3.0 aimed to solve regulations essential to the field. 3.0 included regulatory innovation tasks that would meet the needs of the pharmaceutical industry. After the Regulatory Innovation 3.0 announcement, the MFDS also provided a separate session for the pharmaceutical industry, sharing 3.0’s policy and agenda related to the field of pharmaceuticals. This year, there will be significant changes to the GMP evaluation policy, the department of approval, the clinical trial system, and the post-management of drugs. After the 3.0 announcement, there was significant interest from the pharmaceutical industry regarding the revision of requirements for registering APIs. The GMP evaluation for APIs will be replaced with documents proving the country of origin and PIC/S countries. The MFDS is already discussing internally to revise the regulation related to GMP within this year. They will announce the legislation this month and set a goal to implement the revision by December after hearing experts’ opinions and the review by the Office for Government Policy Coordination. The revision will be made so that facility audits will be substituted with submitting documents for GMP evaluation of APIs starting next year. There were doubts when Regulatory Innovation 1.0 was announced three years ago, but now the industry looks forward to the announcement of 4.0.
