- 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.
- 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 &8361;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.
- General hospitals to prescribe Jeil Pharmaceutical Lonsurf
- by Eo, Yun-Ho Jul 10, 2020 06:13am
- Major general hospitals in Korea are readying prescription of Jeil Pharmaceutical’s Lonsurf indicated to treat patients with colorectal cancer.
According to pharmaceutical industry sources, Lonsurf (tipiracil/ trifluridine) has been passed by drug committees (DCs) at the Big Five&8212;Seoul National University Hospital, Samsung Medical Center, Seoul Asan Medical Center and Severance Hospital.
Jeil Pharmaceutical won the sales license in Korean market over Lonsurf from Japan-based Taiho Pharmaceutical. The drug is indicated to treat patients with metastatic colorectal cancer previously treated with fluoropyrimidine&8209;, oxaliplatin&8209; and irinotecan&8209;based chemotherapy, an anti&8209;vascular endothelial growth factor (VEGF) biological therapy, and an anti&8209;epidermal growth factor receptor EGFR therapy (if confirmed as RAS wild type). It was approved for Korean market in October last year.
The drug uses tipiracil to inhibit thymidine kinase that breaks down trifluridine to maintain the blood concentration.
A clinical study confirmed Lonsurf’s statistically meaningful improvement in overall survival (OS) against the best supportive care and the treatment meeting the primary clinical endpoints. The drug’s safety was also confirmed in another clinical study conducted previously.
As of 2016, according to Korea Central Cancer Registry (KCCR) report, the number of patients diagnosed with colorectal cancer in Korea reached 28,127, coming second after stomach cancer. And the demand for drugs to be used in patients, who do not respond to standard of care, is rising. Specifically, Lonsurf is taking the limelight as a new treatment option that meets the demand.
Lonsurf is approved in 75 countries and regions around the world including Korea as a treatment for metastatic colorectal cancer. In last year, the drug was also indicated to treat metastatic stomach cancer in the U.S., Japan and Europe. The drug globally generates approximately USD 30 million.
The U.S. National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) guidelines respectively recommend Lonsurf as ‘Category 2A’ and ‘Level 1/ Grade B’ to patients with metastatic colorectal cancer who have failed to respond to standard of care.
- 66 companies complain choline alfoscerate coverage reduction
- by Jul 10, 2020 06:13am
- A group of pharmaceutical companies filed a complaint against the government’s decision to reduce coverage on choline alfoscerate drugs.
On July 8, 66 pharmaceutical companies with choline alfoscerate issued a joint statement about their complaint filed for Korea’s Health Insurance Review and Assessment Service (HIRA) to reassess the reimbursement adequacy.
The companies reprimanded the decision contrasts against the government’s objective of adopting selective reimbursement system as the pharmaceutical expenditure among senior citizens would rise significantly, it does not properly reflect social demand on the drug, and they claimed the unreasonable decision goes against the order of executing clinical reevaluation first followed by reimbursement reevaluation.
The 66 companies argued, “Steeply raising the patient copayment rate from 30 percent to 80 percent on some of choline alfoscerate’s indications (mild cognitive impairment and depression) completely contradicts the foundational goal of National Health Insurance coverage enhancement initiative that provides coverage on non-reimbursements (selective reimbursement system) to lower patient’s burden on medical expense and to improve medical accessibility.”
The companies added, “While the global medical scene is still seeking for a proper dementia treatment, lowering the coverage rate on choline alfoscerate that delays the progression of dementia in order to save finance also contradicts the National Dementia Management Program.”
The government's decision would leave no choice for the economically vulnerable senior citizens but to give up on using the drug.
The companies also rebuked the decision does not properly reflect the social demands based on financial impact, medical importance, affected age group, and patient’s financial burden. To accommodate the social demand, the current special case in patient copayment imposes differentiated rate by categorizing depression as a mild case (copayment rate at 40 percent to 50 percent when prescribed in general hospital), and stroke as a severe disease (copayment rate at 5 percent).
However the pharmaceutical companies states the new reevaluation on choline alfoscerate has fixed the copayment rate at 80 percent for all three indications&8212;emotional and behavioral change, senile pseudo-depression, and secondary symptoms induced by mild cognitive impairment and stroke with risk of progressing into dementia.
They also complained the order of reimbursement reevaluation was shuffled. The companies criticized, “Generally, drugs undergo reimbursement listing procedure after receiving an item approval, but choline alfoscerate had its reimbursement feasibility evaluation before re-verifying the safety and efficacy of the drug,” and “as a result, the affected pharmaceutical companies’ motivation to conduct the clinical reevaluation on choline alfoscerate has greatly diminished.”
The 66 companies urged, “Choline alfoscerate has been prescribed for over two decades in Korea, and even the clinicians stress the reimbursement should be reevaluated based on the Ministry of Food and Drug Safety’s (MFDS) approval details.”
On June 11, HIRA has decided to grant selective reimbursement on choline alfoscerate after reevaluating the drug’s reimbursement feasibility.
A patient diagnosed with dementia taking choline alfoscerate drug to improve symptoms like cognitive impairment would maintain the copayment rate of 30 percent. But patient prescribed with the drug without the diagnosis would pay 80 percent of the pharmaceutical expense as copayment.
- 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.
- 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.
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.