- by Lee, Tak-Sun Apr 21, 2021 05:50am
Attention has been rising on the reason for the delayed approval of the imported AstraZeneca’s COVID-19 vaccine, which was the first vaccine to submit its application in Korea.
Although the Ministry of Food and Drug Safety (MFDS) had shortened the review period to 40 days, 3 months have passed and no news on the approval of the imported product has been heard to date. This means that Korea’s procurement of AstraZeneca vaccines depends solely on the local supply produced by SK Bioscience.
On January 4th, AstraZeneca had submitted two applications for its vaccine; one for the manufacture and marketing authorization of its products manufactured by its CMO SK Bioscience, and the other for the import authorization of products manufactured outside of Korea, including those from Italy.
The ‘Korea AstraZeneca’s COVID-19 Vaccine Inj.’ which is manufactured under a CMO deal by SK Bioscience was been approved on February 10th and became the first COVID-19 vaccine to receive marketing authorization in Korea. The approval process took only 40 days through a rolling review by MFDS.
However, the application for the imported product that was submitted the same day is still under review.
Regarding the matter, an MFDS official explained, “The GMP site data is known to be insufficient. It seems that the submission of supplementary data by the company is being delayed due to the global use of the vaccine.” However, he added that the review process will not take long.
Among the AstraZeneca vaccines in use, 1.57 million doses (for 780,000 people) that were secured via independent contracts were approved for national lot release on February 17th. However, due to the limited supply, authorities are having trouble speeding up the vaccination process.
Fortunately, an additional 7 million doses are expected to be introduced from May to June to be used for vaccination of those aged 65 or older
However, regrets remain as the approval of the imported vaccine would have made procurement much easier.
3 types of vaccines &8211; Pfizer and Janssen’s vaccines in addition to the AstraZeneca vaccine produced by SK bioscience &8211; are currently approved in Korea. On the 12th, GC Pharma, which is responsible for the domestic distribution of the Moderna vaccine, applied for approval. All vaccines other than the AstraZeneca vaccine are imported products.
The prevailing opinion is that we need more locally manufactured vaccines for better procurement. In the same line, the possibility of Moderna establishing a subsidiary in Korea for local production of vaccines has been raised. In the ‘Moderna plans to establish a subsidiary in Korea’ report, Byung-Gook Park, a researcher at NH Investment & Securities stated that “Moderna had mentioned the possibility of establishing a subsidiary in Korea in its second Moderna Vaccines Day held on the 15th. It plans to strengthen its vaccine capability by establishing subsidiaries in Korea, Japan, and Australia this year.”
For a locally manufactured Moderna vaccine to be introduced to the market, the company would need to submit an additional marketing authorization application for the drug to MFDS.
- Schingles is expected to be released in the end of the year
- by Apr 21, 2021 05:50am
- GSK's Schingles, which boasts the highest efficacy among the existing shingles vaccines, is expected to receive product approval at the end of the year as soon as possible. When Schingles is released in Korea, fierce competition is expected with Zostavax and Sky Zoster.
According to the pharmaceutical industry on the 21st, GSK applied for Schingles item approval from the MFDS in January and is currently undergoing review. Approval is expected within the year, considering the period of time it normally takes for a permit review. It is expected that it will be able to obtain a permit at the latest early next year. Schingles was first approved in the United States in October 2017 and in Europe and Japan.
In the US, the market share reached 98% a year after the launch of Schingles. Worldwide sales amounted to ￦1.1 trillion in 2018, ￦2.5 trillion in 2019, and ￦3 trillion in 2020.
The defense rate is stronger than other products. In a clinical trial involving adults 50 years and older (ZOE-50), Schingles demonstrated a 97.2% ERA at 3.2 years of follow-up. Those over 70 years old (ZOE-70) showed 89.8% efficacy after 3.7 years of follow-up.
The conventional vaccine, MSD's Zostavax, showed 51% protection in patients over 50 years of age. It was 41% of those over 70 years old. SK Bioscience's Sky Zoster has no known ERA figures. With a non-inferiority test against Zostavax, it can be assumed that the ERA is similar. Schingles is an inactivated vaccine, unlike the live attenuated vaccine Zostavax, and is particularly recommended for patients with weakened immunity.
Accordingly, the CDC recommended Schingles first over existing products as a shingles vaccine for adults over 50 years of age. People who had previously been vaccinated with Zostavax also recommended Schingles re-vaccination.
Schingles has two doses and is a bit more expensive. Zostavax and Sky Zoster are given a single dose, whereas Schingles requires two doses at intervals of 2 to 6 months. The price is also expected to be higher than the two products.
Concerns over Schingles' supply shortages are reported to be largely resolved. At the time of launch, there was a shortage of supply due to failure to keep up with demand. Accordingly, GSK is continuously expanding its production capacity and increasing its supply.
Currently, the domestic shingles vaccine market includes Zostavax and Sky Zoster. Originally, Zostavax was the only one, but with the launch of Sky Zoster in October 2017, it quickly eroded the market. Market sales of Zostavax and Sky Zoster based on IQVIA last year were ￦43.2 billion and ￦29.1 billion, respectively.
Competition between the three products will be fierce from next year when Schingles sales are in full swing.
- Lynparza tablet to be prescribed at Big 5 hospitals
- by Eo, Yun-Ho Apr 21, 2021 05:49am
The tablet formulation of the anticancer drug ‘Lynparza’ can now be prescribed at the Big-5 tertiary hospitals.
Industry sources reported that AstraZeneca’s poly ADP ribose polymerase (PARP) inhibitor Lynparza (olaparib) passed the review of drug committees (DC) in the five major hospitals, the ‘Big-5s,’ which include the Samsung Medical Center, Seoul National University Hospital, Seoul St. Mary’s Hospital, Asan Medical Center, and Severance Hospital. With Severance Hospital’s DC giving the last nod, Lynparza has now landed in all five hospitals as well as 25 other medical institutions nationwide.
As the company received approval from HIRA's Drug Review Evaluation Committee (DREC) to reimburse Lynparza for the ‘first- and second-line maintenance treatment of patients with BRCA-mutated ovarian cancer,’ prescriptions are expected to be made soon after being listed for reimbursement.
The company had submitted an application to expand Lynparza tablet's reimbursement to ▲first-line maintenance treatment for patients with BRCA-mutated advanced ovarian cancer; ▲second-line or higher maintenance monotherapy for patients with recurrent platinum-sensitive advanced epithelial ovarian cancer; and ▲HER-2 negative metastatic breast cancer; however, reimbursement for second-line treatment of mBRCA-negative ovarian cancer and breast cancer patients were rejected in the listing process.
The addition of the tablet formulation also signifies an improvement in the convenience of oral administration for patients. In the SOLO-2 trial, which investigated the efficacy of the tablet formulation of Lynparza, the 300mg of the tablet formulation taken twice a day met the primary efficacy endpoint.
The recommended dose of the Lynparza tablet is two 150mg tablets (300 mg) taken orally twice daily, while the dose for the Lynparza capsule is eight 50mg capsules (400mg) taken orally twice daily. The total number of pills to take is reduced from 16 to 4 per day with the tablet formulation.
Lynparza was listed for ovarian cancer in October 2017 as an expenditure cap type under the Risk Sharing Agreement (RSA) through the PE exemption policy.
However, the coverage only applied for its use as maintenance therapy for 15 months following chemotherapy. Due to the period limit, cases of patients being discontinued reimbursement started to arise from January 2019. To resolve the issue, the government and AstraZeneca discussed expanding the reimbursement and lifted the period limit set on the drug.
- The domestic COVID-19 vaccine is still some way off
- by Lee, Jeong-Hwan Apr 21, 2021 05:49am
- It was pointed out that amid intensifying competition in countries around the world over the supply and demand of COVID-19 vaccine, there is a low possibility that a domestic vaccine will be marketed within this year, increasing public anxiety.
Compared to the fact that about three domestic-made COVID-19 treatments are expected to be marketed within the year, domestic vaccines are planned to be used in a phase 3 clinical trial at the end of the year, so they can only be approved for use next year. This was revealed through the 'COVID-19 Treatment and Vaccine Domestic Clinical Support Status' data submitted by the KHIDI.
It is estimated that the government is supporting ￦71 billion for R&D for the development of a domestic COVID-19 treatment and ￦34 billion for the vaccines.
The domestic companies that are developing COVID-19 treatments that are receiving government support are 4 pharmaceutical companies including Celltrion, and 5 pharmaceutical companies including SK Bioscience for vaccines.
In the case of COVID-19 treatment, Celltrion's Regkirona received CMA in February of this year and is using it, and the blood system treatment under development of GC Pharma is also scheduled to apply for CMA in April. Daewoong is receiving support for the development of two treatments, and CMA is expected in the second half of this year.
As for the vaccine, SK Bioscience, Genexine, Geneone Life Science, CELLID, and EUBIOLOGICS are in clinical trials with government support. However, it is currently in the early stages of phase 1 or 2 clinical trials, and it is expected to enter phase 3 in the second half of this year, so it is unlikely that marketing approval will be possible within this year.
Rep. Jeon Bongmin said, "Recently, people are feeling anxious about the supply and demand of COVID-19 vaccine. It is regrettable that the development of this year is difficult in the current situation." He added, "The government should prepare measures to relieve public anxiety related to the supply and demand of vaccines as soon as possible."
- Korean bio-pharma companies attract attention at AACR 2021
- by Whang, byung-woo Apr 21, 2021 05:49am
- The AACR 2021 Annual Meeting, the largest meeting on cancer research in the world, took place from April 10th to April 15th. At the meeting, new combination therapies were introduced, raising expectations for the use of new mechanisms of action in the field of cancer treatment.
Through a presentation of data on the use of nivolumab (Opdivo) in early-stage non-small cell lung cancer (NSCLC), Bristol Myers Squibb (BMS) presented its next target area for its PD-1/L1 inhibitor. Bayer appealed the efficacy of its PI3K inhibitor copanlisib (Aliqopa) in combination with rituximab.
Results of Combination therapy studies show potential to expand treatment scope
The presentation that first drew attention was the latest clinical data on Opdivo, which was one of the first PD-1 inhibitors approved in the field of immuno-oncology.
Patients with early-stage NSCLC who received the Opdivo-chemotherapy combination before surgery were nearly 14 times more likely to show no signs of cancer cells in their resected tissue than those who received only chemotherapy.
The findings came from the Phase III CheckMate-816 trial, which enrolled patients with stage IB to IIIA NSCLC. BMS explained that this was the first time for a presurgery use of the Opdivo-chemotherapy combination to show a significant improvement in the complete pathological response in patients with earlier stage NSCLC
More specifically, 24% of patients receiving the Opdivo-chemotherapy combination had a pathological complete response (pCR) which was defined as no residual viable tumors in their resected tissues and lymph nodes, compared with 2.2% in the chemotherapy alone arm,
Also, pathological response in patients in the Opdivo combination group was 36.9%, significantly higher than the 8.9% in the chemotherapy alone group.
Patrick Forde, professor at Johns Hopkins University said, “For the first time in a phase III trial, we see the potential for an anti-PD-1 immunotherapy to improve outcomes in earlier-stage NSCLC. We are highly encouraged by the marked improvement in pCR, the overall good tolerability, and the absence of impact on surgery feasibility when nivolumab is added to neoadjuvant chemotherapy,”
Bayer had presented the role of PI3K inhibitors in treating patients with indolent non-Hodgkin’s lymphoma (iNHL) who relapsed after at least one prior therapy with the combination of its copanlisib (Aliqopa) and rituximab (Rituxan).
The data was from the Phase III Chronos-3 trial, in which patients were randomly assigned to copanlisib-rituximab combination (307 patients) or placebo-rituximab combination (151 patients)
After a median follow-up of 19.2 months, the study met its primary endpoint of progression-free survival (PFS), showing a 48% reduction in the risk of lymphoma progression or death in the copanlisib-rituximab arm.
The overall response rate (ORR) was 80% in the copanlisib-rituximab arm and 47.7% in the placebo-rituximab arm. The complete response rate (CRR) was 33.9% in the copanlisib-rituximab arm, compared to the 14.6% in the placebo-rituximab arm.
Regarding the results, Bayer stated that Aliqopa was the first PI3K inhibitor to demonstrate superior efficacy in combination with Rituxan with a manageable safety profile in patients with relapsed iNHL.
Also, Lilly presented the potential of its Retevmo to be approved for indications other than those reived for lung cancer and thyroid cancer with RET abnormalities.
At the annual meeting, Lilly announced that Retevmo shrunk tumors in 47% of patients with RET fusion-positive cancers originating from different sites in the body other than the lung and the thyroid in a Phase 1/2 study.
In particular, Lilly emphasized that more than half of the patients still showed benefits after a median follow-up of 13 months.
The 47% tumor response rate presented at the 2021 AACR was generated from 32 patients that had 12 unique cancer types with RET fusion. Over 60% of patients had treatment-resistant gastrointestinal cancers that typically do not respond well to targeted therapy.
Based on such data, the company said it plans to take the ‘tumor agnostic' approach with Retevmo.
Increasing the response rate with combination therapies…compatibility between candidate substances?
Clinical research by domestic biopharmaceutical companies presented at AACR mostly ended at preclinical trial outcomes or examining the potential of combination therapies. However, some showed promise by drawing a response rate from patients that did not respond to existing drugs.
At the poster session held on the 12th, PharmAbcine presented the nonclinical data of its immune-oncology drug candidate PMC-309. PMC-309 is showing promise as an immunotherapeutic strategy to be used alone or in combination for patients who showed no response to existing immune-oncology drugs by inhibiting a new immune checkpoint.
PMC-309 is a monoclonal IgG (Immunoglobulin G) that targets human VISTA (V-domain Ig Suppressor of T cell Activation), an immune checkpoint regulator.
The nonclinical study results show that PMC-309 increased T cell activities in in-vitro settings with its anti-VISTA effect. In in vivo studies using a human VISTA Knock-In mouse model, the tumor growth inhibition was significantly higher for the PMC-309 group compared to the control group. The tumor growth inhibition rate was comparable to the PD-1 administered group and showed a possible synergistic effect when used in combination with existing immunotherapy.
The company plans to evaluate the potential toxicity risk of PMC-309 this year to submit for the IND (Investigational New Drug)-enabling studies, and expects to enter the clinical stage next year.
ABL Bio presented the preclinical trial results of its bispecific antibody dual immune checkpoint blockade that includes the target LAG-3, an emerging next-generation immuno-oncology drug.
ABL501 is a bispecific antibody that simultaneously targets both PD-L1 and LAG-3. Recently, BMS announced successful results of a Phase II/III trial using its anti-LAG-3 antibody(elatlimab) in combination with its PD-1 inhibitor (nivolumab) in patients with melanoma, bringing the candidate substance one step closer to commercialization.
In-vitro and in-vivo assessments of the drug demonstrated that ABL501 showed better anti-tumor effect than the PD-L1and LAG-3 combination therapy. With such positive results, the drug was evaluated to have potential as a new alternative to patients who did not see an effect with existing PD-1 or PD-L1-based therapies.
ABL Bio plans to submit a Phase 1 Investigational New Drug Application (IND) based on the data.
MedPacto presented the potential to use its immune-oncology drug Vactosertib as a combination therapy.
The combination of Vactosertib and Onivyde was found to significantly reduce metastasis of cancer cells and greatly improved survival rates compared to Onivyde alone.
In the 50-day study of the combination using animal models, the survival rate of the group that was not administered Vactosertib and the group that used the current established treatment was 23% and 53% respectively. However, the Vactosertib combination group’s survival rate improved to reach 84%. This suggests the potential of the combination as a new treatment option.
Also, Qurient announced the results for its CDK-7 inhibitor ‘Q901’ and received attention for its potential as an alternative for patients developing resistance. Although the study is yet in its in-vivo stages, Q901 showed tumor growth inhibition effect in mice that developed resistance to the CDK4·6 inhibitor (Ibrance), suggesting its potential in patients who developed resistance to existing breast cancer treatments that may found in clinical studies in the future.
- Generics for Eliquis are sold out
- by Apr 20, 2021 09:13am
- The production and sales of generics that lost Eliquis(Apixaban)' patent dispute were halted. According to the drug distribution industry on the 16th, generic for Eliquis companies stopped producing and selling items at once after the Supreme Court ruling. There is some inventory that has been passed to wholesalers.
Generics for Eliquis have been released since June 2019 ▲Chong Kun Dang's Liquisia ▲Yuhan’s Yuhan Apixaban ▲Samjin's Elxaban ▲Hanmi’s Apixban ▲Yooyoung’s Yupix, and ▲Huons’ Apiquis. The Supreme Court overturned the court case on the 8th and sided with the patent holder, BMS. Distribution was stopped in preparation for compensation for damages in the final judgment.
The Supreme Court overturned the court case on the 8th and turned to the side of the patentee, BMS. Unless a new allegation is raised, the judgment of the superior court is usually followed.
Accordingly, domestic companies began to stop sales in preparation for a lawsuit for damages that BMS will file. They sent an official letter to the retailer, saying, ``We will stop production and sales after it is sentenced according to the decision to abolish the court's judgment in the court below.
Most of the pharmacy-only online malls were sold out, except for some wholesalers that had left stock. Representatively, Chong Kun Dang’s Liquisia 2.5mg is out of stock, and only 8 of Liquisia 5mg are in stock. Since the amount of damages is determined in proportion to the amount of sales, it seems that generic companies have quickly stopped selling.
Generic for Eliquis market has grown significantly over the past year. The generic market, which had sales of \1.2 billion in 2019, expanded 622% to \8.3 billion in 2020. This contrasts with the 2.6% decline in sales of original Eliquis. However, if the Supreme Court verdicts at the remand of revocation, the generic can only be released after September 2024.