Fam-trastuzumab deruxtecan-NXKI

The final overall survival result for post-surgery Herceptin, Perjeta and chemotherapy in early-stage HER2-positive breast cancer was statistically significant. Roche’s Herceptin and Perjeta duo is already part of a well-established standard of care in early-stage HER2-positive breast cancer. Now, the company can further back up the regimen’s prowess with a decade’s worth of survival data. The drugmaker evaluated a post-surgery Herceptin, Perjeta and chemotherapy regimen over ten years in its phase 3 APHINITY study of 4,804 patients. The regimen slashed the risk of death by 17% compared to those who took Herceptin, chemotherapy and placebo without Perjeta. The final overall survival result was statistically significant, according to Roche.To put it another way, 91.6% of those treated with the Perjeta-based regimen were alive at ten years compared to 89.8% in the control arm, Roche’s Genentech unit reported Tuesday. For those with early-stage HER2-positive disease, the results “validate the sustained benefits of the Perjeta-based regimen,” Genentech’s chief medical officer and head of global product development, Levi Garraway, M.D., Ph.D., said. “These long-term data reinforce the regimen’s value as a well-established standard-of-care treatment in the curative setting.”The company also noted a 21% reduction in the risk of death for the group of patients with lymph node-positive disease, supporting Perjeta’s addition to standard post-surgical treatment as “most beneficial for people with HER2-positive breast cancer with lymph node-positive disease who are at high risk of recurrence,” study chair and CEO of research institute German Breast Group Forschungs, Sibylle Loibl, M.D., noted in Genentech’s release.The full study results will be presented on Thursday at the 2025 European Society for Medical Oncology Breast Cancer Congress. Previously, in 2019, Roche presented an early tease of the long-term study with an analysis showing that the Perjeta addition to Herceptin and chemotherapy cut down the risk of death and recurrence by 24% after six years of treatment. At that time, however, Perjeta didn’t beat the Herceptin-chemo combo on the overall survival measure.Perjeta was first approved in 2012 as an add-on to Herceptin and chemotherapy in the metastatic setting based on trial data showing the regimen could significantly extend the amount of time patients lived without their disease worsening. The Perjeta regimen shortly after became the first breast cancer therapy approved for use before surgery and its label was later extended to cover post-surgical adjuvant treatment of HER2-positive breast cancer with high risk of recurrence. These days, Herceptin copycats are now prevalent, but Perjeta is yet to face similar competition, although its time is ticking as Shanghai Henlius Biotech’s Perjeta biosimilar candidate was accepted for FDA review in February. The 10-year adjuvant data update comes shortly after AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu plus Perjeta beat the standard Perjeta, Herceptin and chemotherapy in delaying tumor progression or death for patients with newly diagnosed HER2-positive metastatic breast cancer.Herceptin and Perjeta both remain steady earners for Roche, with Perjeta bringing in about $4.3 billion in 2024 sales and Herceptin contributing some $1.6 billion. Roche is projected to take home the crown as the largest drugmaker by sales in 2025, according to Evaluate analysts. 

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.