Disitamab Vedotin

The latest first-line win from a randomized trial “proves the success of the ‘HER2-ADC + immunotherapy’ combination treatment concept” in bladder cancer, the study’s principal investigator, Guo Jun, M.D., Ph.D., from Peking University Cancer Hospital, said in a statement. The HER2-targeted antibody-drug conjugate that Pfizer gained from its Seagen buyout has delivered positive results in a pivotal study among Chinese patients with newly diagnosed bladder cancer, a readout that bodes well for the New York pharma’s own global phase 3 trial.A combination of the HER2 agent, called disitamab vedotin, and Junshi Biosciences’ PD-1 inhibitor toripalimab outperformed chemotherapy at both delaying tumor progression and extending patients’ lives as a first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma, RemeGen said Monday.The results came from an interim analysis of a Chinese phase 3 trial coded RC48-C016, which has now met its two primary endpoints of progression-free survival and overall survival, according to RemeGen. The company said the improvements were statistically significant and clinically meaningful.RemeGen described the results as “strongly positive.” Benefits were observed regardless of patients’ eligibility for the chemotherapy cisplatin or HER2 expression levels, the company said. The trial enrolled patients with immunohistochemistry (IHC) scores of 1+ or greater.RemeGen now plans to file an approval application in the indication with Chinese authorities. Detailed results from the study will be shared at an upcoming medical meeting. To benchmark the results, industry watchers will want to compare the data with those from Pfizer’s famous EV-302 trial. That study established the company’s Astellas-partnered Nectin-4 ADC Padcev and Merck & Co.’s PD-1 king Keytruda as the standard first-line bladder cancer treatment in a biomarker-unselective population.Meanwhile, the readout bodes well for Pfizer’s own global phase 3 trial that pairs disitamab vedotin with Keytruda in previously untreated HER2-expressing bladder cancer. The trial, coded DV-001 or Keynote-D74, bears a primary completion date in mid-2026, and it’s currently Pfizer’s only phase 3 trial for the HER2-targeted ADC. That study also uses an IHC 1+ cutoff for HER2 expression.The latest first-line win from a randomized trial “proves the success of the ‘HER2-ADC + immunotherapy’ combination treatment concept, and is also a major breakthrough in the global treatment of urothelial carcinoma,” the study’s principal investigator, Guo Jun, M.D., Ph.D., from Peking University Cancer Hospital, said in a statement. Disitamab vedotin, commercially known as Aidixi in China, in 2021 became the first homegrown ADC approved in the country. The initial indication was third-line HER2-overexpressing gastric cancer. That same year, based on a pooled analysis of two phase 2 single-arm studies, the drug followed with a Chinese nod to treat platinum-refractory bladder cancer with HER2 overexpression at IHC 2+ or higher.The HER2 ADC came to Pfizer via its $43 billion acquisition of Seagen, which in-licensed the drug’s ex-Asia rights in 2021 after paying RemeGen $200 million upfront.However, with AstraZeneca and Daiichi Sankyo’s rival ADC Enhertu quickly establishing a leadership position across multiple HER2 indications, disitamab vedotin has remained largely quiet outside China.In its fourth-quarter 2024 earnings report, Pfizer took a $200 million impairment charge for disitamab vedotin, citing “emerging competition.”Besides bladder cancer, one of the drug’s main market opportunities lies in the post-Enhertu breast cancer setting. That market holds great potential, especially after AZ and Daiichi reported that Enhertu showed “highly statistically significant” efficacy as a first-line treatment in HER2-positive breast cancer. However, the post-Enhertu treatment area is also growing increasingly competitive.  China has been a major source of innovation in the hot ADC field. While RemeGen is a pioneer there, the company has also struggled. At the end of 2024, the company counted 926 R&D staffers, down nearly 30% from the prior-year level.In February, RemeGen also lost its chief strategic officer, He Ruyi. He was the former chief scientist of China’s Center for Drug Evaluation and was viewed as a key figure in RemeGen’s transformation into an ADC leader.RemeGen is still investing in Aidixi, having just registered a phase 3 trial testing the drug on top of BeiGene’s PD-1 inhibitor Tevimbra and chemotherapy in first-line HER2-low gastric or gastroesophageal junction adenocarcinoma.The study is being launched about two months after AZ and Daiichi said Enhertu was successful in a second-line stomach cancer study.

YANTAI, China, May 12, 2025 /PRNewswire/ -- On May 12th, 2025, RemeGen Co., Ltd. ("RemeGen", stock symbols: 688331.SH/09995.HK) announced that its phase 3 clinical trial (Study ID: RC48-C016) on disitamab vedotin (DV, brand name: 爱地希®), the first domestically approved antibody-drug conjugate (ADC) in China, in combination with the PD-1 inhibitor toripalimab versus the standard chemotherapy as a first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC) has reached its two primary endpoints of progression-free survival (PFS) and overall survival (OS). Statistically significant differences and clinically meaningful benefits were observed from the strongly positive results of a prespecified interim analysis by Independent Data Monitoring Committee (IDMC). The major subgroup analyses showed that DV combined with toripalimab significantly improved PFS and OS compared with the standard chemotherapy treatment, irrespective of cisplatin eligibility or HER2 expression level. Furthermore, this regimen exhibited manageable safety profile and tolerable adverse reactions. Detailed data of this study are planned to be presented at major international academic conferences later this year. Subsequently, RemeGen plans to file Biologic License Application (BLA) for this indication to the Center of Drug Evaluation of National Medical Products Administration (NMPA) in China. RC48-C016 is a randomized, active-controlled, multi-center phase 3 clinical trial evaluating efficacy and safety of DV plus toripalimab versus gemcitabine in combination with cisplatin/carboplatin in systemic-treatment-naive patients with HER2-expressing (defined as IHC 1+, 2+ or 3+) la/mUC. The study was initiated in June 2022 and conducted in 74 sites across China with 484 patients enrolled. The principal researcher of this study, Professor Guo Jun from Peking University Cancer Hospital, said: "Extremely exciting! We, once again, jointly witnessed a strong positive result of DV combined with toripalimab in the first-line treatment of advanced urothelial carcinoma. Regardless of whether the patients are suitable for cisplatin treatment and regardless of patients' HER2 expression status, DV combined with toripalimab significantly improved PFS and OS. This outstanding efficacy proves the success of the 'HER2-ADC + immunotherapy' combination treatment concept, and is also a major breakthrough in the global treatment of urothelial carcinoma. We look forward to the excellent performance of DV in subsequent studies which should provide better decision-making basis for clinicians, bring more benefits to patients, and reshape the global treatment landscape of urothelial carcinoma with the 'Chinese approach'." SOURCE RemeGen Co., Ltd WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED