Astellas Receives Health Canada Approval for VYLOY® (zolbetuximab) in Combination with Chemotherapy for Advanced Gastric and Gastroesophageal Junction Cancer

• VYLOY is the first and only therapy approved in Canada to target claudin 18.2, a biomarker positively expressed by 38% of patients with advanced gastric cancer^1,2
• Treatment with VYLOY shown to significantly extend both progression-free survival and overall survival in Phase 3 trials^1,2
• Canada's Drug Agency (CDA-AMC) recently issued draft recommendation to reimburse VYLOY with conditions³ .

MARKHAM, ON, Jan. 9, 2025 /CNW/ - Today, Astellas Pharma Canada Inc. is proud to announce that Health Canada has approved VYLOY® (zolbetuximab for injection), which is indicated to be used in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours are claudin (CLDN) 18.2 positive as determined by a validated test. Additionally, the Company is pleased to share that Canada's Drug Agency (CDA-AMC) recently issued a draft recommendation to reimburse VYLOY with conditions.³ 

VYLOY is the first and only approved monoclonal antibody specifically designed to target gastric tumour cells that express the biomarker CLDN18.2, offering a targeted approach to cancer treatment. In the Phase 3 clinical trials, approximately 38 per cent of adult patients with advanced or metastatic gastric or GEJ cancers had tumours that were CLDN18.2 positive.^1,2 By binding to CLDN18.2 expressed on tumour cell membranes, zolbetuximab results in antibody-dependent cellular cytotoxicity, complement dependent cytotoxicity and tumour growth inhibition.⁴

Dr. Elena Elimova, Medical Oncologist, Princess Margaret Cancer Centre
"The symptoms associated with early stage gastric and gastroesophageal junction cancers can often be subtle, leading to many patients receiving a diagnosis at an advanced or metastatic stage with limited treatment options. The advent of personalized medicine has marked a transformative shift in the treatment and management of these cancers. As a medical oncologist working with gastric cancer patients, I look forward to integrating innovative therapeutic options, such as zolbetuximab, into my practice so that our patients with these devastating diseases could have improved outcomes."

Teresa Tiano, Chair & Co-Founder, My Gut Feeling
"Our organization is deeply committed to supporting Canadian patients with stomach cancer. We tirelessly provide peer-to-peer support, education, awareness, and advocacy and have witnessed a remarkable evolution in the treatment landscape, driven by significant investments in research and development. Innovations in personalized medicine, such as zolbetuximab, are ushering in a new era for the treatment and management of cancers like stomach cancer." 

Graham Watson, Business Unit Head, Oncology, Astellas Pharma Canada
"The approval of VYLOY in Canada as the first and only targeted therapy to treat CLDN18.2 positive gastric or GEJ cancer patients marks a significant milestone in our unwavering commitment to advancing scientific progress for challenging diseases. We're also pleased that CDA-AMC provided a positive draft recommendation, which is another key milestone towards making VYLOY available for Canadian patients. Across Astellas, we are proud of our shared vision for precision medicines and the ways they can help transform the management of advanced cancers. With this approval, our local team is ready to support Canadian health care professionals and the gastric and GEJ cancer patients they treat."

Data from the Phase 3 SPOTLIGHT and GLOW clinical trials, which supported Health Canada's authorization, showed that treatment with zolbetuximab provided statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to the standard of care chemotherapies in eligible patients with gastric or GEJ cancers.1^,2 In the SPOTLIGHT trial, a median PFS of 10.61 months was achieved with zolbetuximab plus mFOLFOX6 as first-line treatment, versus 8.67 months with placebo plus mFOLFOX6. The median OS was 18.23 months versus 15.54 months in the respective treatment groups.1 Similar efficacy findings were seen in the GLOW trial where median PFS was 8.21 months versus 6.80 months, and median OS 14.39 months versus 12.16 months, with zolbetuximab plus CAPOX, compared to placebo plus CAPOX, respectively.2 In both the SPOTLIGHT and GLOW trials, the incidence of serious treatment emergent adverse events (TEAEs) was similar in the zolbetuximab treatment groups compared to the controls. The most common all-grade TEAEs reported in the zolbetuximab treatment groups were nausea, vomiting and decreased appetite.^1,2

This regulatory approval for zolbetuximab follows the October 2024 approval by the U.S. FDA, the September 2024 approval by the European Commission (EC), the August 2024 approval by the UK Medicines and Healthcare products Regulatory Agency, and the March 2024 approval by Japan's Ministry of Health, Labour and Welfare.^5,6,7,8 Astellas has submitted further applications for zolbetuximab to other regulatory agencies around the world with reviews ongoing.

About VYLOY (Zolbetuximab)
Zolbetuximab is a claudin 18.2-directed cytolytic antibody that was investigated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours are claudin (CLDN) 18.2 positive. In both the SPOTLIGHT and GLOW Phase 3 clinical trials, approximately 38 per cent of patients screened had tumours that were CLDN18.2 positive, defined as ≥75 per cent of tumour cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining, assessed and confirmed using an in-vitro companion diagnostic test or medical device.^,2 

As an investigational first-in-class monoclonal antibody (mAb), zolbetuximab targets and binds to CLDN18.2, a transmembrane protein expressed on cancer cells. In pre-clinical studies, zolbetuximab reduced the number of CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, leading to tumour growth inhibition.³ 

About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer
Gastric and gastroesophageal junction (G/GEJ) cancers are known to be histologically similar, are recommended to be managed in the same way in treatment guidelines, and frequently display aligned responses to treatment.^2,9 Gastric cancer (GC) is the fifth most common cancer and the fourth leading cause of cancer-related deaths worldwide.¹⁰ In Canada, there were approximately 4,100 new cases in 2023, with an incidence rate of 8.6 per 100,000 people.¹¹

GEJ adenocarcinomas start in the first two inches (5 cm) where the esophagus joins the stomach.¹² GC has a 5-year survival rate of 29 percent in Canada, driving the need for new therapeutic options that can slow disease progression and extend lives.¹³

Because early-stage cancer symptoms frequently overlap with more common stomach-related conditions, G/GEJ cancers are often diagnosed in the advanced or metastatic stage, or once they have spread from the tumour's origin to other body tissues or organs.¹⁴

Early signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, bloating of the stomach after meals, loss of appetite.12 Signs of more advanced G/GEJ cancer can include unexplained weight loss, weakness and fatigue, sensation of food getting stuck in the throat while eating, vomiting blood or having blood in the stool.12 Risk factors associated with G/GEJ cancer can include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD).^15,16

INVESTIGATIONAL STUDIES

About the SPOTLIGHT Phase 3 Clinical Trial
SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumours were CLDN18.2 positive. The study enrolled 565 patients at 215 study locations in the U.S., Canada, United Kingdom, Australia, Europe, South America, and Asia. The primary endpoint is progression-free survival (PFS) of participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability, and quality-of-life parameters.¹

Data from the SPOTLIGHT clinical trial were presented during the 2023 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in an oral presentation on January 19, 2023, and were subsequently published in The Lancet on April 14, 2023.¹ 

For more information, please visit clinicaltrials.gov under Identifier NCT03504397.

About the GLOW Phase 3 Clinical Trial
GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumours were CLDN18.2 positive. The study enrolled 507 patients at 166 study locations in the U.S., Canada, United Kingdom, Europe, South America, and Asia, including Japan. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability, and quality-of-life parameters.² 

Data from the GLOW study were initially presented at the March 2023 ASCO Plenary Series with an updated oral presentation at the 2023 ASCO Annual Meeting on June 3, 2023, and were subsequently published in Nature Medicine on July 31, 2023.² 

For more information, please visit clinicaltrials.gov under Identifier NCT03653507.

Investigational Pipeline in CLDN18.2
An expanded Phase 2 trial of zolbetuximab in metastatic pancreatic adenocarcinoma is in progress. The trial is a randomized, multi-center, open-label study, evaluating the safety and efficacy of investigational zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma with CLDN18.2 positive tumours (defined as ≥75% of tumour cells demonstrating moderate to strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163. In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology area and is currently recruiting patients. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1/1b study in participants with metastatic or locally advanced unresectable gastric or GEJ adenocarcinoma or metastatic pancreatic adenocarcinoma whose tumours have CLDN18.2 expression. The safety and efficacy of the agent under investigation have not been established for the uses being considered. For more information, please visit clinicaltrials.gov under Identifier NCT05365581.

About Astellas Canada
Astellas Pharma Canada, Inc. is a Canadian affiliate of Tokyo-based Astellas Pharma Inc., a pharmaceutical company conducting business in more than 70 countries around the world. At Astellas, we strive to become a cutting-edge, value-driven life science innovator. This means working at the forefront of healthcare change to turn innovative science into VALUE for patients. What sets us apart is our focus on patients, our pioneering innovation, our collaborative culture, and the passion of our talented people. Learn more: https://www.astellas.com/ca/.

Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

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References

¹ Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668.

² Shah MA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141.

³ CDA-AMC. Zolbetuximab. Available at https://www.cda-amc.ca/sites/default/files/DRR/2024/PC0338_Vyloy_DRAFT_REC.pdf. Last accessed January 2025.

⁴ Sahin U, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021;32(5):609-19. 

⁵ Astellas press release issued October 21, 2014: Astellas' VYLOY™ (zolbetuximab-clzb) Approved by U.S. FDA for Treatment of Advanced Gastric and GEJ Cancer. Available at: https://www.astellas.com/en/news/29291. Last accessed: November 14, 2024.

⁶ Astellas press release issued September 20, 2024: Astellas Receives Approval from the European Commission for VYLOY™ (zolbetuximab) in Combination with Chemotherapy for Advanced Gastric and Gastroesophageal Junction Cancer. Available at https://www.astellas.com/en/news/29401. Last accessed December 2024.

⁷ GOV.UK. News story: Zolbetuximab Approved to Treat Adults with Stomach or Gastro-oesophageal Junction Cancer. Available at: https://www.gov.uk/government/news/mhra-approves-zolbetuximab. Last accessed: September 2024.

⁸ Astellas press release issued 26 March 2024: Astellas' VYLOY™ (zolbetuximab) Approved in Japan for Treatment of Gastric Cancer. Available at: https://www.astellas.com/en/news/29026. Last accessed: September 2024.

⁹ Barra WF, et al. GEJ cancers: gastric or esophageal tumors? Searching for the answer according to molecular identity. Oncotarget. 2017; 8(61):104286–104294.

¹⁰ Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. 

¹¹ Brenner, D.R.; Poirier, A.; Woods, R.R.; Ellison, L.F.; Billette, J.M.; Demers, A.A.; Zhang, S.X.; Yao, C.; Finley, C.; Fitzgerald, N.; et al. Projected estimates of cancer in Canada in 2022. CMAJ 2022, 194, E601–E607.

¹² American Cancer Society. About esophagus cancer (03-20-2020). Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8614.00.pdf. Last accessed: September 2024. 

¹³ Brenner, D.R.; Poirier, A.; Woods, R.R.; Ellison, L.F.; Billette, J.M.; Demers, A.A.; Zhang, S.X.; Yao, C.; Finley, C.; Fitzgerald, N.; et al. Projected estimates of cancer in Canada in 2022. CMAJ 2022, 194, E601–E607.

¹⁴ American Cancer Society. Stomach Cancer Early Detection, Diagnosis, and Staging (01-22-2021). Available at https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/signs-symptoms.html. Last accessed: September 2024.

¹⁵ American Cancer Society. Stomach cancer causes, risk factors and prevention (01-22-2021). Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8839.00.pdf. Last accessed: September 2024.

¹⁶ American Cancer Society. Esophageal cancer causes, risk factors, and prevention (06-09-2020). Available at https://www.cancer.org/content/dam/CRC/PDF/Public/8615.00.pdf. Last accessed: September 2024.

SOURCE Astellas Pharma Canada, Inc.

For more information, please contact: Dara Willis, Director, Product & Corporate Communications, Astellas Pharma Canada, Inc., Mobile: [phone], Email: [email protected]