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vyloy becomes the first and only drug approved in the eu targeting cldn18.2. 38% of patients with advanced gastric cancer are positive for cldn18.2 expression1,2

phase iii study results showed that treatment with monoclonal antibodies targeting cldn18.2 significantly prolonged progression-free survival and overall survival1,2

tokyo, september 20, 2024-- astellas pharma inc. (tse: 4503, president and ceo: naoki okamura, “astellas”) today announced that the european commission has approved vyloy® (zotuximab) in combination with fluorouracil- and platinum-containing chemotherapy for the first-line treatment of adult patients with human epidermal growth factor receptor 2 (her2)-negative, claudin (cldn) 18.2-positive locally advanced, unresectable or metastatic gastric or gastroesophageal junction (gej) adenocarcinoma. the european medicines agency recommended maintaining orphan drug designation for zotuximab based on poor survival outcomes for patients with gastric and gej cancers.

zotuximab is the first and only approved monoclonal antibody specifically designed and used to target gastric tumor cells expressing the biomarker cldn18.2, which provides a more personalized approach to cancer treatment. in the phase iii clinical study of zotuximab, approximately 38% of adult patients with advanced unresectable gastric and gastroesophageal junction cancer were positive for cldn18.2 expression. 1,2 by binding to cldn18.2 expressed on the tumor cell membrane, zotuximab can induce antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and inhibit tumor growth. 3

zorana maravic, ceo of digestive cancer europe (dice)

"unfortunately, because early symptoms are often similar to those of many common benign stomach diseases, gastric and gej cancers are often not diagnosed until the advanced or metastatic stage, when traditionally treatment options are relatively limited. ensuring timely diagnosis, followed by personalized treatment and care, is critical to the patient's survival and quality of life."

moitreyee chatterjee-kishore, phd, mba, senior vice president and head of immuno-oncology development, astellas

"we are pleased to bring our first-in-class targeted therapy, zotuximab, to patients in europe, where gastric and gastroesophageal cancer is the sixth leading cause of cancer-related death. the approval of zotuximab ushers in a new era of precision medicine for advanced cancers and reflects our continued commitment to pioneering scientific discoveries to improve patient outcomes."

the european marketing authorization was supported by results from two phase iii clinical studies, spotlight and glow. the results showed that treatment with zotuximab in eligible patients with gastric and gej cancers showed statistically significant improvements in progression-free survival (pfs) and overall survival (os) compared with other standard chemotherapy. 1,2 in the spotlight study, the median progression-free survival was 10.61 months for zotuximab plus mfolfox6 as first-line treatment, compared with 8.67 months for placebo plus mfolfox6. the median overall survival was 18.23 months and 15.54 months, respectively. 1 in the glow trial, the median progression-free survival was 8.21 months for the zotuximab plus capox group, compared with 6.80 months for the placebo plus capox group, and the median overall survival was 14.39 months and 12.16 months, respectively. 2 in the spotlight and glow studies, the incidence of serious treatment-emergent adverse events (teaes) was similar between the zolpidem and control groups. the most common all-grade teaes reported in the zolpidem group were nausea, vomiting, and decreased appetite. 1,2

the european marketing authorization for zolpidem is valid in all 27 european union (eu) member states, as well as iceland, liechtenstein and norway, and is consistent with the recently updated esmo gastric cancer guidelines, which state that zolpidem can be used in combination with chemotherapy as a first-line treatment option for patients with her-2-negative, cldn18.2-positive, metastatic gastric cancer.4 astellas is working closely with local regulatory authorities and health technology assessment agencies in the eu to ensure that patients who may benefit from zolpidem have access to new treatments as quickly as possible.

prior to the eu approval, the uk medicines and healthcare products regulatory agency approved zolpidem in august 2024, and japan's ministry of health, labour and welfare formally approved it in march 2024. 5,6 astellas has submitted marketing applications to other regulatory authorities around the world, and these applications are currently under review.

astellas has already factored in the impact of this approval in its financial forecast for fiscal year 2024 (ending march 31, 2025).

about zotuximab

zotuximab is an investigational cytolytic antibody targeting claudin 18.2, indicated in combination with fluorouracil and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced, unresectable or metastatic gastric or gastroesophageal junction (gej) adenocarcinoma that is human epidermal growth factor receptor 2 (her2)-negative and claudin (cldn) 18.2-positive. in the phase iii spotlight and glow studies, approximately 38% of screened patients were cldn18.2-positive, defined as moderate to strong membranous staining of cldn18 in ≥75% of tumor cells, as assessed and confirmed using an in vitro companion diagnostic test or medical device. 1,2 astellas is collaborating with roche to develop the ventana® cldn18 (43-14a) rxdx test, which, if approved, will be used by pathologists or laboratories to identify patients who are candidates for targeted therapy with zotuximab. 7 this immunohistochemistry-based companion diagnostic is currently under review.

zotuximab is an investigational monoclonal antibody (mab) targeting claudin 18.2 (cldn18.2) that binds to cldn18.2, a transmembrane protein. preclinical studies have shown that zotuximab reduces the number of cldn18.2-positive cells through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, leading to tumor growth inhibition.

about locally advanced unresectable metastatic gastric cancer and gastroesophageal junction cancer

gastric cancer and gastroesophageal junction (g/gej) cancer are histologically similar, are managed in the same way according to treatment guidelines, and often show consistent responses to treatment. 2,8 in 2022, there will be more than 135,000 new cases of gastric cancer in europe. 9 gastric cancer is the sixth most common cause of cancer-related death in europe, with 95,431 deaths in 2022. 9,10 gastroesophageal junction (gej) adenocarcinoma begins in the first two inches (5 cm) where the esophagus joins the stomach. 11 the average five-year survival for european patients with gastric and g/gej cancer, regardless of disease stage, is 26%, meaning new treatment options are needed to slow disease progression and prolong life. 12

because the symptoms of early-stage gastric cancer are often similar to those of many common benign stomach diseases, gastric cancer is often diagnosed in the late or metastatic stages, or after cancer cells have spread from the primary tumor site to other tissues or organs in the body.

early signs and symptoms may include indigestion or heartburn, abdominal pain or discomfort, nausea and vomiting, bloating after meals, and loss of appetite. 13,14 symptoms of advanced stomach cancer may include unexplained weight loss, weakness and fatigue, a choking sensation during meals, and vomiting or blood in the stool. 13,14,15 risk factors associated with stomach and gej cancer may include increasing age, male sex, family history, helicobacter pylori infection, smoking, and gastroesophageal reflux disease (gerd). 16,17

research trials

about the spotlight phase iii clinical trial

spotlight is a global, multicenter, double-blind, randomized phase iii trial evaluating the efficacy and safety of zotuximab plus mfolfox6 (a combination of oxaliplatin, leucovorin, and fluorouracil) versus placebo plus mfolfox6 as first-line treatment for patients with cldn18.2-positive, her2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. the study enrolled 565 patients at 215 sites in the united states, canada, the united kingdom, australia, europe, south america, and asia (including china). the primary endpoint was progression-free survival (pfs) in subjects treated with zotuximab plus mfolfox6 versus those treated with placebo plus mfolfox6. secondary endpoints included overall survival (os), objective response rate (orr), duration of response (dor), safety and tolerability, and quality of life parameters. 1

the clinical trial data from spotlight was presented in an oral presentation at the 2023 american society of clinical oncology (asco) gastrointestinal cancers symposium on january 19 and was subsequently published in the lancet on april 14.

about the glow phase iii clinical trial

glow is a global, multicenter, double-blind, randomized phase iii trial evaluating the efficacy and safety of zotuximab plus capox (a combination chemotherapy regimen including capecitabine and oxaliplatin) versus placebo plus capox as first-line treatment for patients with cldn18.2-positive, her2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. the study enrolled 507 patients at 166 centers in the united states, canada, the united kingdom, europe, south america, and asia (including china). the primary endpoint was progression-free survival (pfs) in patients treated with zotuximab plus capox compared with patients treated with placebo plus capox. secondary endpoints included overall survival (os), objective response rate (orr), duration of response (dor), safety and tolerability, and quality of life parameters. 2

the glow study data was initially presented at the american society of clinical oncology (asco) plenary meeting in march 2023, and was invited to give an oral presentation on the study data at the 2023 asco annual meeting on june 3, and was subsequently published in the journal nature medicine on july 31.

targeting cldn 18.2 research product pipeline

a phase ii extension trial in metastatic pancreatic cancer is ongoing. this trial is a randomized, multicenter, open-label study designed to evaluate the safety and efficacy of zolutuximab combined with gemcitabine plus nab-paclitaxel as first-line treatment for patients with cldn18.2-positive metastatic pancreatic cancer (i.e., moderate to strong staining of cldn18 in ≥75% of tumor cells as determined by a validated immunohistochemical assay).

in addition to zolpidem, our primary focus is on asp2138, which is being developed by the immuno-oncology development team. asp2138 is a bispecific monoclonal antibody that binds to cd3 and claudin 18.2 and is currently in a phase 1/1b clinical trial in patients with gastric cancer, gastroesophageal junction adenocarcinoma, or pancreatic cancer. the safety and efficacy of the investigational drug have not yet been demonstrated in the application area in question.

there is no guarantee that these investigational drugs will receive regulatory approval for commercial use in the applications being investigated.