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- 2025-12-22 17:41:56
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- Will Eylea K-biosimilar overcome evergreening in the U.S.?
- by Hwang, Byung-woo Jul 16, 2024 05:48am
- The expiration of the U.S. substance patent for the blockbuster biopharmaceutical Eylea (aflibercept) is expected to spark competition in the biosimilar market. Samsung Bioepis, which preemptively received marketing authorization for an Eylea biosimilar, is stuck in a patent dispute with Regeneron, which owns the original Eylea. It is expected that other latecomers will also face a tough time entering the market depending on Regeneron’s patent response. Pic of Eylea Eylea is a treatment for eye diseases such as macular degeneration that binds to vascular endothelial growth factor (VEGF) and inhibits neovascularization. The drug generated global market sales of KRW 13 trillion. Of these, the U.S. market accounts for USD 5.719 billion in sales, accounting for a 62% share. Currently, Eylea’s patent has expired in Korea and its biosimilar has been launched into the market, and the patent is scheduled to expire in May 2025 in Europe. In the U.S., the product patent expired in June of this year, but the other patents will expire as follows: ▲formulation patent in 2027, ▲ regimen patent in 2032, ▲purification and batch patent in 2040 The difference between biosimilar entry in Korea and the United States is in the existence of patent disputes. In Korea, Bayer, which sells Eylea, did not file a patent suit, so there was no problem with the launch of Eylea biosimilars. However, in the U.S., Regeneron filed a patent infringement lawsuit against Celltrion and Samsung Bioepis in November last year. Regeneron patent defense remains a hurdle in the Eylea market...launch timing remains in question Samsung Bioepis is the company facing an immediate issue due to the patent suit. In May, the U.S. Food and Drug Administration (FDA) approved Samsung Bioepis' Eylea biosimilar, Opuviz, along with India's Biocon Biologics' Yesafili, as the first biosimilars. However, on June 15, the U.S. District Court for the Northern District of West Virginia granted Regeneron's motion for a preliminary injunction against Samsung Bioepis, which prevents Opuviz from launching in the United States. Samsung Bioepis immediately filed an appeal against the preliminary injunction, but the appeal is expected to take 6 months to a year. A Samsung Bioepis official said, “We have no position on the patent dispute that we can disclose at this time.” While it is difficult to predict the outcome of the patent dispute, the general consensus is that the ruling aligns with Regeneron’s intent as the request for a preliminary injunction has been granted. "In the current situation where the product patent has already expired, it is important to determine whether the formulation patent is infringed, and Samsung Bioepis or Celltrion must prove that the patent has not been infringed," said an official from the Korean Intellectual Property Office. "Regeneron's strategy will be to delay the launch of the similar by claiming patent infringement." "In addition to the remaining formulation patent, Regeneron's dosing regimen patent expires in 2032, among others, so the company has an evergreen strategy in place and does not need to hasten the process. The Korean company can appeal to the federal court, but that will also take time, so the originator has an advantage." Considering this, it is difficult to gauge the exact timing of Opuviz’slaunch as its launch is banned until the end of the patent dispute. Given the nature of biosimilars, where multiple competitors enter the market at the same time, it is important to arrive first into the market. However, in this situation, it is unclear whether the biosimilar companies will be able to enjoy the advantage of first approval. The industry believes this is a red flag for Celltrion as well, as the company has also completed applying for U.S. FDA marketing authorization for its biosimilar. However, the result may differ, as there have been cases like Humira where the original and generic companies discussed royalty payments to enable earlier market launch of the generics. AbbVie had delayed the launch of Humira biosimilars beyond the product patent term by building a patent barrier, but Amgen agreed to pay royalties on the remaining patents and released the first Humira generic. "At the time, the industry expected Humira’s generic release to be a long battle as well, but discussions were dramatically held, allowing for the generic’s launch last year,” said an industry official. "If the company feels that it has been extended Eylea’s patent long enough, there is a possibility that the timing of the launch of its generics could be coordinated through similar discussions.”
- Company
- Bladder cancer drug Balversa lands in KOR 1.5yr after apvl
- by Eo, Yun-Ho Jul 15, 2024 05:47am
- The new bladder cancer drug Balversa may now be prescribed, one year and a half after being approved in Korea. According to industry sources, Janssen Korea’s FGFR targeting urothelial carcinoma (bladder cancer) drug Balversa (erdafitinib) recently passed Seoul Asan Medical Center’s drug committee (DC) review. Balversa was approved by the Ministry of Food and Drug Safety in January 2022. Specifically, the drug is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with FGFR2 or FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy, which includes platinum-based chemotherapy, or whose disease has progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy. However, the approval of PD-1 and PD-L1-directed immuno-oncology agents in the first- and second-line settings that followed Balversa’s approval led to the need for Balversa todemonstrate efficacy in patients who previously received these agents. The situation was addressed with the publication of Balversa’s Phase III THOR trial study, which demonstrated a prolonged overall survival (OS) benefit with Balversa over chemotherapy in patients with metastatic urothelial carcinoma with FGFR3/2 gene alterations whose disease progressed after first-line treatment with immuno-oncology agents. In the study, Balversa prolonged overall survival (OS) compared with chemotherapy in patients with metastatic urothelial carcinoma. Results showed that over a median follow-up of 15.9 months, the mOS was 12.1 months in the Balversa arm, reducing the risk of death by 36% compared with the 7.8 months in the chemotherapy arm. Based on these findings, the U.S. Food and Drug Administration (FDA) granted Balversa formal approval in January, but with a more restricted indication than originally approved, and the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recently recommended expanded indications for Balversa. Janssen Korea has also additional submitted results from the THOR study to Korea’s Ministry of Food and Drug Safety. Therefore, the company well may launch Balversa in earnest in the second half of the year. It remains to be seen whether Balversa will be able to go beyond landing in medical institutions and gain insurance coverage in Korea. Meanwhile, bladder cancer is one major cancer that has lacked a targeted therapy option. Balversa is the first targeted anti-cancer drug for bladder cancer with a novel mechanism of action that inhibits fibroblast growth factor receptor (FGFR). FGFR is a biomarker involved in cancer cell growth that is associated with various cancers. FGFR mutations are particularly common in bladder cancer, with 20 to 30% of patients carrying mutations.
- Company
- Severe asthma drug 'Fasenra' lands in general hospitals
- by Eo, Yun-Ho Jul 15, 2024 05:47am
- AstraZeneca Korea’s Fasenra (benralizumab) has passed the drug committees (DC) of tertiary general hospitals. ‘Fasenra,’ a severe asthma treatment, has been listed for insurance reimbursement this month and is now available for prescriptions at general hospitals. Industry sources said that AstraZeneca Korea’s Fasenra (benralizumab) has passed the drug committees (DC) of tertiary general hospitals, including Samsung Medical Center in Seoul, Seoul National University, Seoul Asan Hospital, and Seoul St. Mary’s Hospital, and medical institutions, including Kyungpook National University Hospital, Pusan National University Hospital, Seoul National University Bundang Hospital, Ajou University Hospital, Chonnam National University Hospital, and Chungnam National University Hospital. Since July 1st, Fasenra has been approved for reimbursement. Severe eosinophilic asthma accounts for most of the cases of severe asthma. The basis of Fasenra’s approval was improvements in patients with severe eosinophilic asthma: up to 87% of the patients treated with Fasenra no longer had advanced asthma. The drug can be reimbursed when treating patients with severe eosinophilic asthma who are inadequately controlled despite treatment with high-dose inhaled corticosteroid-long-acting beta-agonist (ICS/LABA) and long-acting muscarinic antagonist (LAMA). In detail, the following criteria should be met: ▲Within the year before starting treatment, the eosinophil count in the blood was 300 cells/㎕ or higher, and within the first year of treatment, systemic oral corticosteroids (OCS) were required for acute exacerbations four or more times, or within 6 months before starting therapy, systemic oral corticosteroids were continuously administered, or ▲The eosinophil count in the blood was 400 cells/㎕ or higher within the year before starting treatment. Systemic corticosteroids were required for acute exacerbations three or more times within the first year of treatment. Severe eosinophilic asthma accounts for approximately 84% of severe asthma cases. It involves frequent exacerbations and may lead to reduced quality of life despite treatment with high-dose inhaled corticosteroids and other conventional therapies. In particular, when symptoms are not controlled, even with asthma controllers, oral steroids may be necessary. However, long-term use of these medications is associated with systemic side effects such as osteoporosis, hypertension, and diabetes. Therefore, biological agents are recommended to reduce the dosage of these treatments. Fasenra is a targeted biologic agent that binds directly to interleukin-5 receptor alpha (IL-5Rα) expressed on eosinophils' surface, inducing cell apoptosis. It has been demonstrated to reduce blood eosinophil counts rapidly within one day of administration. In the global Phase 3 SIROCCO clinical study, enrolling 1205 severe eosinophilic asthma patients worldwide, including Korea, Fasenra administered at 8-week intervals showed a 51% reduction in annual asthma exacerbation rates compared to placebo after 48 weeks of treatment. In the CALIMA study, Fasenra treatment also resulted in a 28% reduction in annual asthma exacerbation rates compared to placebo.
- Company
- K-Bios make progress in new rare lung cancer drug dev
- by Son, Hyung-Min Jul 15, 2024 05:47am
- The c-MET-mutation-targeted NSCLC drugs that are being developed by Korean pharma and biotech companies have been recognized for their potential. Recently, Abion Bio signed an agreement with Janssen to receive Leclaza (lasertinib) free of charge. This agreement will allow Abion Bio to commercialize the combination of its in-development vabametkib and Leclaza for the treatment of lung cancer. InnoCure Therapeutics’s targeted therapy has been recognized for its value by being selected as a national new drug development project According to industry sources on the 13th, Johnson & Johnson’s subsidiary Janssen will provide domestic biotech Abion Bio free lasertinib for its EGFR-positive non-small cell lung cancer (NSCLC) clinical trial. Abion Bio’s NSCLC drug candidate in development is vabametkib, which targets the c-MET mutation. c-MET is a protein expressed by the mesenchymal-epithelial transition (MET) gene. It is one of the proteins that transmit signals to cells and is considered a typical oncogene and is associated with the development of various solid cancers, including lung, colon, stomach, and liver cancers. It is estimated that 6% of patients with non-small cell lung cancer harbor a c-MET mutation. Janssen will be testing lasertinib’s potential in EGFR-positive NSCLC in combination with Abion Bio’s vabametkib. Approximately 30-40% of patients with EGFR-mutated NSCLC develop a c-MET mutation after receiving a prior EGFR targeting therapy. In clinical results, vabametkib demonstrated an objective response rate (ORR) of 52.9% in patients with c-MET-mutated NSCLC who failed prior treatment. In previously untreated patients, the ORR was 75%. In terms of safety, vabametkib’s incidence of grade 3 or higher treatment-related adverse events (TRAE) was 10%. This was lower than the TRAE rates of 38% and 28% identified with Novartis' Tabrecta and Merck's Tepmetko. Abion is aiming to develop vabametkib as a treatment for EGFR-mutant NSCLC in combination with Leclaza and as monotherapy for MET-mutant NSCLC. InnoCure develops c-MET-mutated lung cancer treatment with target protein degrader InnoCure Therapeutics has also made progress in the development of c-MET lung cancer therapies. Recently, the company's new drug candidate was selected as an R&D project to support the establishment of a new drug ecosystem that is being organized by the Korea Drug Development Fund. InnoCure develops new drugs with next-generation target protein degrader (TPD) technology. The company is focused on the development of new drugs for non-small cell lung cancer by utilizing its main technologies, ELKBIL, NEOELKBIL platform, and its oral formulation platform MILPROTAC. InnoCure Based on its TPD technology, Innocure has been developing a c-MET targeted inhibitor for the treatment of NSCLC. With the selection of this new drug development project, the company plans to derive new drug candidates and conduct research to enter clinical trials. While there is a treatment available for MET exon 14 deletion among c-MET mutations, no other targeted therapies are available on the market. InnoCure Therapeutics aims to address this unmet need by degrading the c-MET target protein.
- Company
- K-Bio speeds up novel drug development to treat MASH
- by Son, Hyung-Min Jul 15, 2024 05:47am
- The biotech industry in South Korea has made notable achievements in treating MASH. Many pharmaceutical companies have failed in clinical trials to develop a treatment for MASH due to its complex pathogenesis. As the first treatment for MASH has been approved, the industry draws attention to the success of the commercialization of other new drug candidates of various pharmaceutical companies that entered clinical trials in South Korea. On July 11th, the current trend in the MASH treatment development was discussed during the Bioplus-Interphex Korea 2024 (BIX 2024), sponsored by the Korea Biotechnology Industry Organization (Korea Bio) and RX Korea. MASH was previously known as Non-Alcoholic Steatohepatitis (NASH). International academic associations, such as the American Association for the Study of Liver Diseases (AASLD), agreed upon the use of the term Metabolic dysfunction-associated steatohepatitis (MASH). Developing treatment for MASH has been challenging until now. However, the first novel drug to treat MASH in March became available after the U.S.-based Madrigal Pharmaceuticals’ Rezdiffra was approved. The late-comers eye on the opportunity to develop the second potential novel drug development through various mechanisms. Lee Seul-ki, D&D pharmatech CEO D&D pharmatech has entered a phase 2 trial in the United States. The company has recently received approval for its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA). DD01’s phase 2 trial will be conducted across 10 institutions in the United States, enrolling 68 patients with MASH-accompanying overweight and obesity. DD01 is an agent targeting both GLP-1 and glucagon. In preclinical trials, D&D pharmatech’s DD01, an agent targeting both GLP-1 and glucagon, has shown a significant decrease in liver fat and a weigh loss effect. DD01’s effect has been maintained in a phase 1 trial. The phase 1 trial evaluated the drug tolerance and safety of DD01 and placebo in patients with MASH accompanied by obesity instead of in healthy adults. The clinical results demonstrated that a 4-week DD01 treatment reduced liver fat by 52%. These results were similar to those of the 1-year treatment with semaglutide (57% reduction) or Tirzepatide (47% reduction). High-dose (80 mg) DD01 treatment reduced liver fat by 30% in all patients. In contrast, the placebo’s reduction effect was shown in 8% of all patients. Lee Seul-ki, D&D pharmatech’s CEO, said, “We believe that glucagon plays an important role because many obesity patients also have MASH. Clinical studies reported that glucagon therapy reduces liver fibrosis by 50-80%.” Lee added that “DD01 is formulated with GLP-1 and glucagon in a ratio of 10:1. In a preclinical study, DD01 demonstrated to maintain the effect of GLP-1 as well as the effect of glucagon.” “We need a drug that effectively regulates blood glucose and weight to treat MASH. GLP-1 drugs that can quickly elevate blood glucose have adverse reactions, such as dizziness and vomiting. For DD01, we confirmed that it is more slowly released into the blood than other therapies. Additionally, we received approval of an IND application for a new protein therapy targeting collagen synthesis and investigating the potential of various novel drugs,” Lee commented. OliX Pharmaceuticals is developing a new drug candidate, OLX75016, to treat MASH. OLX75016 works by inhibiting MARC1 expression, which is related to the pathogenesis of MASH and reducing liver fat. June Hyun Park, OliX Pharmaceuticals Director OliX Pharmaceuticals has recently entered a phase 1 trial for OLX75016 in Australia and started the first patient administration. Notably, OliX Pharmaceuticals is investigating the possibility of using OLX75016 in combination with novel drugs targeting GLP-1 and glucagon. Since most MASH treatments target GLP-1, OliX Pharmaceuticals plans to develop treatments that have distinguished mechanisms and improve synergistic effects with GLP-1 agents. In a preclinical trial, OLX702A demonstrated effects in reducing liver fat and reversing liver fibrosis. June Hyun Park, OliX Pharmaceuticals Director, said, “Fibrosis contributes to deaths associated with liver. We are confirming the role of MARC1 in liver fibrosis. As we confirm MARC1 as an important factor in fibrosis, we are exploring the potential of novel drug development.”
- Company
- Protein C deficiency drug 'Ceprotin' begins negotiations
- by Eo, Yun-Ho Jul 12, 2024 05:48am
- Takeda Pharmaceuticals Korea 'Ceprotin' has entered the last stage of obtaininig reimbursement listing. According to our investigation, Takeda Pharmaceuticals Korea has started to negotiate drug pricing with the National Health Insurance Service (NHIS) for Ceprotin (Human potein C), a novel drug for the treatment of congenital protein C deficiency. ‘Human protein C deficiency’ is a type of thrombotic disease that causes blood clotting and it was first reported in 1981. 'Severe congenital protein C deficiency,' a type of protein C deficiency, is an extremely rare disease that occurs in one in every 4 million. In South Korea, there have been reported cases of 13 patients to date (according to 2019 KOSIS statistics). Congenital protein C deficiency is a hereditary disorder that occurs when the body lacks ‘protein c,’ a naturally occurring thrombolytic agent in the body, due to genetic abnormalities. On average, healthy individuals have a 'protein C' level of around 100 ng/dL. However, patients with severe congenital protein C deficiency are known to have less than 1% of normal levels (less than 1 ng/dL), disrupting the balance between blood clotting and anticoagulation. This imbalance results in frequent thrombosis, recurrent venous thrombosis, venous stasis ulcers, and pulmonary embolism. These symptoms can lead to high-risk conditions such as myocardial infarction or stroke. Additionally, it occurs when blood vessels become blocked due to thrombosis, causing bleeding throughout the body, the most common manifestation is large, purplish patches resembling bruises on the skin. Currently, there is no known drug therapy that can prevent or fully control venous thrombosis and purpura fulminans (PF) in patients with severe congenital protein C deficiency. Ceprotin is a concentrated solution of human protein C made from human protein C. It received the Orphan Drug Designation from the Ministry of Food and Drug Safety (MFDS) in March 2021. Based on an early phase clinical study, enrolling 18 patients with severe congenital protein C deficiency, Ceprotin was demonstrated to be effective in treating purpura fulminans (PF) or other thrombotic events compared to the histological control group. In the study, 18 patients with purpura fulminans (PF) (6 severe, 11 moderate, and 1 mild) were treated with Ceprotin. 17 patients (94.4%) were assessed as 'effective,' 1 patient (5.6%) as 'effective with complications.' There were no reports of 'ineffective' outcomes. This result demonstrated more effective treatment outcomes than a control group (21 patients), which received traditional therapies such as fresh frozen plasma or traditional anticoagulants. In the secondary efficacy rating of Ceprotin, out of 18 cases of purpura fulminans (PF), 13 cases (72.2%) were evaluated as 'excellent,' 4 cases (22.2%) as 'good,' and 1 case (5.6%) of severe purpura fulminans (PF) was assessed as 'fair.' Additionally, out of the 5 cases of venous thrombosis, 4 cases (80%) were evaluated as 'excellent' and 1 case (20%) as 'good'. Furthermore, Ceprotin effectively reduced the size and number of skin lesions. Non-necrotic skin lesions were treated within a maximum of 12 days (median 4 days), while necrotic skin lesions were treated within a maximum of 52 days (median 11 days) with this drug.
- Company
- Will Epkinly become a game-changer in the blood cancer mkt?
- by Hwang, Byung-woo Jul 12, 2024 05:47am
- The arrival of bispecific antibody-based therapies in Korea is expected to shift the blood cancer treatment market paradigm. The industry is welcoming the introduction of a new treatment option, as an unmet need exists in diffuse large B-cell lymphoma (DLBCL), which has a poor prognosis even after three or later lines of treatments. AbbVie hosted a press conference on the 10th to highlight the significance of Epkinly’s approval. Professor Jin Seok Kim. Department of Hematology-Oncology at Severance Hospital, is presenting data related to blood cancer.AbbVie hosted a press conference on the 10th to celebrate the launch of 'Epkinly (epcoritamab)’ as a third-line treatment for DLBCL and highlight the implications of the approval. Epkinly was approved by the Ministry of Food and Drug Safety in late June for the treatment of adult patients with relapsed or refractory DLBCL who have received 2 or more prior systemic therapies. Epkinly is a humanized bispecific antibody (IgG1) that binds to CD20 on B cells and CD3’s extracellular specific epitopes on T cells. It has a mechanism of action that induces specific T-cell activation and T-cell-mediated CD20-expressing cell death by simultaneously acting on CD20-expressing cancer cells and CD3-expressing endogenous T cells. Epkinly is the first subcutaneous bispecific antibody approved in Korea for the treatment of DLBCL. It has the advantage of being administered in less than one minute, allowing for a relatively short hospital stay and rapid treatment. The duration of the treatment is not limited and can be administered until disease progression or unacceptable toxicity Epkinly’s approval is noteworthy because it provides a new option in the treatment of DLBCL, an area with much unmet need. Professor Deok Hwan Yang, Department of Hematology-Oncology at Chonnam National University Hwasun Hospital, said, "Even after receiving first-line standard therapy for DLBCL, 30 to 40% of patients relapse or become refractory to treatment and move on to the next line of treatment. Patients who relapse after receiving autologous stem cell transplantation as a second-line treatment have poor prognosis, and patients who relapse after receiving CAR-T as a third-line treatment also have poor outcomes." This means that patients who relapse after receiving three or more lines of treatment generally have a poor prognosis, with lower overall response rates and worse survival outcomes. "Currently, there are limited options in the third and later lines of treatment, with no set standard of care. In this way, there is a large unmet need for new options.” (From the left) Professor Deok Hwan Yang, Department of Hematology-Oncology at Chonnam National University Hwasun Hospital; Professor Jin Seok Kim. Department of Hematology-Oncology at Severance HospitalThe study that became the basis of Epkinly’s approval is the EPCORE NHL-1 study, a non-randomized, single-arm trial. Its efficacy analysis showed an overall response rate (ORR) of 62%, with 39% achieving complete response (CR). Professor Jin Seok Kim. Department of Hematology-Oncology at Severance Hospital, said, “We found Epkinly was well tolerated in heavily pretreated third-line patients, and most adverse events were manageable and predictable. At 30 months of follow-up, median overall survival (mOS) was 19.4 months, confirming that it is a viable option for prolonging survival in this patient population." The advent of such bispecific antibody-based therapies sheds light on the question of how they will compare to CAR-T therapies that are being reimbursed through national health insurance. Experts predict that bispecific antibody therapies such as Epkinly will become complementary options in the future, assuming that they also be reimbursed. Professor Kim explained, "If you look at the average cost, I think they will be very similar to CAR-T therapies, and I don't think one can be a substitute for the other. I think it's going to be a patient-specific choice because they have different targets, but I think there will be cost concerns."
- Company
- "Enhertu gets expanded indication to treat lung cancer"
- by Son, Hyung-Min Jul 11, 2024 06:12am
- Ahn Myung Ju, Professor of the Division of Hematology-oncology in the Department of Medicine at Samsung Medical Center “Previously, patients could only use Enhertu by participating in clinical trials conducted in tertiary general hospitals. Current approval in South Korea will provide a new treatment option for patients with HER2 mutant metastatic non-small cell lung cancer (NSCLC). Brain metastasis is common in lung cancer patients. Because Enhertu demonstrated a response rate of 50% in patients with brain metastasis, it is clinically significant.” During a recent meeting with Daily Pharm, Ahn Myung Ju, Professor of the Division of Hematology-oncology in the Department of Medicine at Samsung Medical Center, highly regarded the clinical value of Enhertu (ingredient: trastuzumab deruxtecan). Enhertu, an antibody-drug conjugate (ADC) jointly developed by Daiichi Sankyo and AstraZeneca, has been approved for the treatment of HER2-positive breast cancer and gastric cancer. As Enhertu demonstrated to be effective in HER2 mutant NSCLC and HER2-low breast cancer, its indication was expanded in May. HER2 mutant NSCLC is a rare cancer that occurs in about 2-4% of patients with NSCLC. Previously, the treatment of this cancer with chemotherapy and immunotherapy for cancer was limited, and HER2-targeted therapy showed inconsistent results. Therefore, there has been an unmet need for an effective treatment option to increase the survival in patients. Previously, several targeted treatment options, such as Hanmi Pharm’s poziotinib, were tested for the treatment of HER2 mutant NSCLC but failed to demonstrate efficacy. Therefore, Enhertu is likely to provide new hope to patients with HER2 NSCLC, which is categorized as a rare cancer. Ahn said HER 2 mutation gained attention in NSCLC after the availability of next-generation sequencing (NGS) testing and targeted therapies like Enhertu. It will provide a new treatment opportunity to patients with NSCLC. Enhertu is approved in South Korea based on phase 2 trials Enhertu is an ADC that targets HER2 mutations by linking an antibody to a payload that destroys tumor cells. This treatment works by binding antibodies to specific antigens, triggering an Antibody-Dependent Cellular Cytotoxicity (ADCC) reaction, and allowing the payload to enter tumor cells and exit through their membranes. This mechanism results in a bystander effect, enabling the destruction of cancer cells, including those without HER2 mutations, demonstrating its anti-tumor efficacy. Enhertu is effective in various diseases, including breast cancer, gastric cancer, colorectal cancer, and NSCLC. In DESTINY-Lung02 study, Enhertu demonstrated antitumor response to the second-line treatment of HER2 mutant metastatic NSCLC. This study evaluated the efficacy and safety in patients with advanced, unresectable, or metastatic NSCLC who have previously been treated with systemic therapy, including platinum-based chemotherapy, more than once. The clinical results demonstrated that Enhertu had confirmed ORR of 49%, complete response (CR) of 1%, and partial response (PR) of 48%. The mean duration of response (DOR) was 16.8 months. “Previously, the second-line treatment, docetaxel, showed a response rate of only 10-15% and a median progression-free survival (PFS) of just 5-6 months. In contrast, Enhertu showed a response rate of 50% and a durable response period lasting up to 16 months. Moreover, brain metastasis is commonly found in lung cancer, and Enhertu has demonstrated an intracranial objective response rate (IC-cORR) of over 50%, even in patients with brain metastasis,“ Ahn said. “Kadcyla, previously used for HER2-positive breast cancer, showed a response rate of over 50% in non-small cell lung cancer (NSCLC) but had limitations due to the short duration of response. In this context, Enhertu has recently gained attention for demonstrating efficacy in HER2-mutated metastatic NSCLC patients,“ Ahn said. ”Although it’s a phase 2 single-arm study, Enhertu demonstrated better outcomes than data from existing medications, warranting consideration for reimbursement,“ Ahn added. "Enhertu use will be greater" in HER2 NSCLC In the case of metastatic non-small cell lung cancer (NSCLC) with HER2 mutation, it represents about 2-4% of all NSCLC cases.This cancer type is characterized by adenocarcinoma histology, prevalence in non-smokers and females, and a higher incidence among East Asian populations, including Japan and Korea. Additionally, it exhibits a higher rate of brain metastases. HER2 abnormalities are categorized into ‘gene mutations,‘ ‘gene amplifications,‘ and ‘protein overexpression.‘ In most cancers, such as gastric cancer and breast cancer, HER2 abnormalities mainly manifest as an overexpression of the HER2 protein. Previously, HER2 overexpression gene abnormalities were generally considered to not play a significant role in NSCLC. First-generation platinum-based chemotherapy has traditionally been the standard treatment for HER2 mutant non-small cell lung cancer. Recently, combination therapies of platinum-based chemotherapy and immunotherapy for cancer have also been employed. However, non-smokers are known to have a poorer response to immunotherapy for cancer, leading to worse prognosis. “So far, in HER2-mutated metastatic non-small cell lung cancer (NSCLC), drugs like Giotrif (afatinib), which is developed to target Epidermal Growth Factor Receptor (EGFR) mutations, have been used, but their response rates have been low, around 10%,“ Ahn said. “Additionally, poziotinib showed a better response rate of approximately 27%, but its use has been challenging due to significant toxicity and side effects,“ Ahn added. Ahn said that Enhertu will bring many changes to the treatment of NSCLC. “In the United States, Enhertu is indicated for the treatment of HER2 mutant metastatic NSCLC with the U.S. FDA approval, and it is widely used with reimbursement coverage. Even in Europe with stringent standards, non-small cell lung cancer patients are strongly recommended to undergo HER2 mutation testing, and those with HER2 mutations are advised to use Enhertu,“ Ahn said. “It is unfortunate that patients cannot afford the monthly cost of approximately 7 to 8 million won for Enhertu, which allows them to maintain their daily lives for over a year. Therefore, it would be beneficial if the government explores various measures, such as selective reimbursement, to alleviate the financial burden on patients, even if it means slightly increasing the portion they pay out of pocket,“ Ahn emphasized.
- Company
- Will Trodelvy be deliberated for reimb by DREC in August?
- by Eo, Yun-Ho Jul 11, 2024 05:47am
- The road to reimbursement for the new ADC breast cancer drug Troldelvy remains a bumpy one. The agenda remains pending for 8 months now. Gilead Sciences' triple-negative breast cancer (TNBC) drug Troldelvy, whose reimbursement request received 100,000 consents in a public petition, was not presented for deliberation to the Health Insurance Review and Assessment Service's Drug Reimbursement Evaluation Committee in July. The drug’s application has remained without progress since its reimbursement standard was set by the Cancer Disease Review Committee in November last year. Therefore, attention is now focused on whether the drug will be submitted to DREC in August. Trodelvy is already listed in about 30 countries around the world. Taiwan, which has a single-payer healthcare system similar to South Korea's, began reimbursing Trodelvy in February this year. The global rush to improve patient access to Trodelvy has been driven by the poor treatment environment for metastatic triple-negative breast cancer and the clinical value of Trodelvy. Triple-negative breast cancer is an aggressive form of breast cancer that recurs and metastasizes rapidly. Patients with metastatic triple-negative breast cancer who have metastasized despite treatment have a life expectancy of only a few months even with chemotherapy. However, chemotherapy has long been the standard of care due to the lack of targets that can effectively kill cancer cells. Trodelvy, the first Trop-2-targeted antibody-drug conjugate (ADC), is the only treatment for metastatic triple-negative breast cancer in the second-line or higher setting that has been shown to prolong survival compared to chemotherapy and has settled as the global standard of care since its introduction. Currently, major guidelines in the U.S. and Europe specify Troldelvy as the preferred agent for patients with previously treated metastatic triple-negative breast cancer. In a Phase III study, the overall survival of the chemotherapy arm was 6.9 months, compared to a nearly one-year survival. (11.8 months) in the Troldelvy arm, In addition, Troldelvy demonstrated an effect in controlling symptoms and pain caused by cancer and an improvement in patients' quality of life by improving their overall health status. Trodelvy was awarded the highest possible score of 5 points on ESMO-MCBS, the European Society for Medical Oncology's (ESMO) scale used to rate the value of anticancer drugs. A score of 5 indicates that a drug is effective not only in prolonging patient survival but also in improving quality of life, and Troldelviy is the only treatment for metastatic triple-negative breast cancer to receive a score of 5 on ESMO-MCBS. In fact, the U.K. has detailed the rationale behind its assessment, stating that the state’s reimbursement decision was based on the severity of metastatic triple-negative breast cancer and the survival benefit of Troldelvy. Similar to Korea, the U.K. uses the incremental cost-effectiveness ratio (ICER) to evaluate new drugs for health insurance coverage. While the UK has one of the highest reimbursement barriers for new drugs, it applies flexible pharmacoeconomic evaluation criteria for innovative drugs used for serious conditions to improve patient access. In the UK, Troldelvy was granted preferential economic evaluation because it prolonged survival in terminally ill patients with less than 2 years of life expectancy, whose population is even smaller than those of rare diseases. As a result, Trodelvy gained access with an ICER threshold that was approximately twice higher than that of general drugs. Meanwhile, Troldelvy has been the subject of a series of petitions this year, gathering more than 100,000 consents online. Since the petition system’s inception, Trodelvy is the only drug to be referred to the National Assembly for garnering more than 50,000 signatures. The Korean Alliance of Patients' Organizations also responded to the desperate pleas of patients and their caregivers when the petition was abandoned due to the expiration of the 21st National Assembly's term. In May, the organization submitted a letter directly to the Ministry of Health and Welfare requesting a prompt review of the reimbursement of drugs with high patient demand, including Trodelvy.
- Company
- From obesity to brain diseases...expansion of GLP-1 agonists
- by Son, Hyung-Min Jul 11, 2024 05:46am
- In-Young Choi, Head of R&D at Hanmi Pharmaceutical The domestic pharmaceutical bio industry is looking into the possibility of developing various new drugs with GLP-1 agents. As Novo Nordisk and Lilly's GLP-1-based obesity drugs have become global blockbusters, latecomers are also avidly developing jumping in to develop the next blockbuster. Major domestic companies are conducting clinical studies on the use of GLP-1 agents not only for obesity, focusing on the mode of administration and quality of weight loss effects, but also in the field of degenerative brain diseases such as metabolism-associated steatohepatitis (MASH) and Alzheimer's disease. On July 10, the Korea Biotechnology Industry Association and RX Korea hosted the BIOPLUS-INTERPHEX KOREA 2024 (BIX 2024). At the event, major Korean pharma and biotech companies introduced their GLP-1 drug candidates. GLP-1 drugs can be effective in weight loss by increasing satiety and improving insulin secretion and sensitivity, resulting in favorable glycemic control. Recently, GLP-1 agents have been reported to be effective against cardiovascular diseases and kidney diseases, and various clinical studies are underway on their use in patients with alcoholism and dementia. At the event, Hanmi Pharmaceutical introduced its new drug candidate for obesity which has a novel mode of action. The company is developing HM15275, an obesity drug candidate that simultaneously acts on glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. HM15275 recently entered a Phase 1 clinical trial in the U.S. To date, a dual GLP-1-GIP receptor agonist Zepbound has been released, but there is no commercialized triple agonist that also includes glucagon. Hanmi Pharmaceutical is aiming to launch a first-in-class drug in this category. In preclinical trials, HM15275 showed less muscle mass loss and higher weight loss than Lilly's obesity drug tirzepatide (Zepbound). In-Young Choi, Head of R&D at Hanmi Pharmaceutical, said, "There are three strategies to developing a third-generation obesity drug following Wegovy and Zepbound. The strategies include increasing the dose, targeting a new mode of action (MOA), or adding substances such as glucagon that can increase the weight loss effect. We are exploring all possibilities through our various pipelines.” Choi added, "There is still an unmet demand for the weight loss effects of GLP-1 obesity drugs such as Zepbound and Wegovy, and the quality of weight loss and reduction of the weight rebound will be the indicators of competitiveness." Mi-Kyung Kim, Vice President and Head of Research HQ at Dong-A ST Also at the event, Mi-Kyung Kim, Vice President and Head of Research HQ at Dong-A ST, introduced its company’s new obesity drug DA-1726. According to Kim, The company completed preclinical studies and is in Phase I clinical trials for DA-1726., with the first patient dosing in April of this year. DA-1726 is a new drug candidate that is being developed as a long-acting oxyntomodulin peptide analog for the treatment of obesity. It acts simultaneously on both GLP-1 and glucagon receptors to suppress appetite, stimulate insulin secretion, and increase basal metabolism in the periphery, ultimately leading to weight loss and glycemic control. In preclinical trials, DA-1726 demonstrated similar weight loss efficacy despite higher food intake compared to tirzepatide, with less rebound after weight loss compared to tizetapide. Kim explained, "The U.S. Food and Drug Administration (FDA) requires a weight loss effect of 5% or more for an obesity drug, but the market is looking for more. We are focusing on the quality of weight loss." GLP-1 agents show promise in MASH·brain disorders GLP-1 drugs are also showing promise in the field of brain diseases. Recently, the mechanism of action of GLP-1 drugs that block neuroinflammatory responses by targeting microglia has been discovered, and active clinical studies are underway on their use in Parkinson's disease and Alzheimer's disease. There is already evidence that GLP-1s are associated with a reduced risk of developing dementia. A study of 88,381 patients with type 2 diabetes aged 65 years and older who were treated with liraglutide-based Victoza showed that those taking Victoza had a lower risk of dementia than those in the other treatment groups. Seulki Lee, CEO of D&D Pharmatech Among domestic companies, D&D Pharmatech is conducting clinical trials of GLP-1 agents in various areas, including Parkinson's disease and dementia. However, in 2020, D&D Pharmatech failed to demonstrate efficacy in a Phase II clinical trial involving 255 patients with Parkinson's disease. The primary endpoint, symptom improvement after a total of 36 weeks of treatment, did not show a statistically significant effect compared to placebo. A closer look revealed a significant difference between the NLY01 and placebo groups at 24 weeks post-dose. However, between weeks 24 and 36, the placebo group showed more improvement than NLY01. D&D Pharmatech is also conducting clinical studies on GLP-1 agents in MASH as well as neurodegenerative diseases. Recently, the company received the U.S. Food and Drug Administration's (FDA) IND approval to initiate a global Phase II trial for DD01, a new drug candidate for MASH. The Phase II trial will enroll 68 overweight and obese patients with MASH at 10 clinical sites in the U.S. D&D Pharmatech’s DD01 is a GLP-1-glucagon dual receptor agonist that has demonstrated weight loss and fatty liver reduction in preclinical studies. In a Phase I trial, DD01 reduced fatty liver by more than 50% at 4 weeks of treatment. Seulki Lee, CEO of D&D Pharmatech, said, "Although we did not meet the primary endpoint while developing a new drug for Parkinson's disease, we have seen potential. Our current focus is on metabolic diseases. We are looking forward to further clinical results based on the promise we have seen with GLP-1 agents in MASH."
