Fam-trastuzumab deruxtecan-NXKI

iStock, Jorm Sangsorn In comments posted in response to the Trump administration’s pharma tariff investigation, companies and industry groups offered solutions to ease the impacts if the plan must go ahead. Despite billions being committed to reshoring pharma manufacturing in the face of tariff threats from President Donald Trump, industry does not seem prepared to entirely forgo foreign operations. In particular, rare disease biotechs and those developing complex modalities like cell and gene therapies have urged the Trump administration to provide exemptions to pending pharma tariffs. The pleas come in the form of comments filed over the past few weeks on the government’s Section 232 investigation being conducted to determine if tariffs can be levied against pharma companies as a matter of national security. “With 95% of the more than 10,000 known rare diseases still lacking an FDA-approved therapy, it is in the interest of the public health to preserve incentives that sustain this innovation ecosystem for rare diseases,” BioMarin wrote in its seven-page letter. The company has a handful of approved gene therapies such as Roctavian for hemophilia A as well as new medicines for diseases that have long lacked options, but has struggled to break even. BioMarin’s is one of hundreds of comments posted last week via the Federal Register. Combing through them reveals the broad issues that companies and industry groups have with the proposed import taxes. The Alliance for Regenerative Medicine (ARM) said that tariffs could undermine and slow access to cell and gene therapies for U.S. patients. If tariffs are put into place, ARM urged the administration to do so in a phased approach that would provide time for companies to reshore production. Small volume imports could also be exempted, the group said. ARM explained that regenerative medicines are sometimes produced for just a handful of patients in a year and demand can be highly variable. But when they are needed, the situation is often time-critical, meaning companies require certainty that they can access the needed ingredients, which often come from outside the U.S. “To ensure patient access, manufacturers must have confidence that they can secure ingredients from the widest possible set of reliable sources, at a predictable cost,” the group said. ARM asserted that even though the patient population for cell and gene therapies is small, losing access to them would be devastating. “Disrupting access to these therapies will cut off some of the most vulnerable and complex patients in our healthcare system from life-changing treatment,” the group’s comment read. The Rare Disease Company Coalition similarly advocated for its patient community by requesting that orphan drugs and their components be exempted from tariffs. The group is run by executives from rare disease companies including Fulcrum Therapeutics, AstraZeneca’s rare disease subsidiary Alexion, argenx, Travere Therapeutics, Sarepta Therapeutics and Inozyme Pharma. “Efforts to rapidly reshore the entire supply chain for orphan drugs, including those in development and those already approved, would be economically prohibitive,” RDCC wrote. “Orphan drug manufacturers lack economies of scale and often depend on highly specialized overseas partners for producing and packaging the final dosage form.” BioMarin said it has recently become profitable after years of reinvesting the bulk of its revenue back into R&D. This was possible thanks to the Orphan Drug Act, which was enacted by Congress with the goal of ensuring that all trade policies support incentives for orphan drug development. The company requested that orphan drugs be excluded from potential tariffs. “Tariffs on these finished products and critical inputs would have an immediate and disproportionate effect on the availability and affordability of orphan drugs,” BioMarin wrote. “Increased costs and supply disruptions could delay treatment development, constrain manufacturing capacity, and threaten timely access to life-saving medicines for patients who have no therapeutic alternatives.” Complex Cancer Drugs Perspective Therapeutics, a biotech developing radiopharmaceuticals, also asked for leniency considering the highly specialized manufacturing process for its complex radiation therapeutics. While some of the comment from CEO Thjis Spoor was blacked out, he asked the Trump administration to defer tariffs on the specialized equipment needed to manufacture its radiopharmaceutical cancer therapies. The company already conducts most of its work in the U.S., having spun out of research at the University of Iowa and operating two stateside manufacturing sites. Japanese biopharma Daiichi Sankyo touted the success of its AstraZeneca-partnered cancer antibody drug conjugate (ADC) Enhertu, and follow-up drug Datroway, as success stories that have benefitted cancer patients in the U.S. But as with radiopharmaceuticals, ADCs are complex to manufacture, with the potential for batch-to-batch variations. Enhertu is manufactured at facilities in the U.S., Japan and Europe, then packaged in Ohio before warehousing and distribution from Tennessee. “Moving the overseas manufacturing steps to the U.S. would require significant overhaul of the company’s operations and substantial financial costs,” Daiichi explained. The company is already moving some additional processes to the U.S. in the coming years, but the second step—production of the conjugated product—is done overseas and would be hit by tariffs if imposed. “The application of tariffs to Enhertu and Daiichi Sankyo’s other medicines risks real consequences on the company’s ability to meet its goals for significant investment in the future of new treatments for patients and planned manufacturing capacity in the U.S.,” Daiichi wrote.

AstraZeneca and Daiichi Sankyo’s ENHERTU plus pertuzumab showed a median progression-free survival greater than three years First trial in more than a decade to demonstrate an improvement in outcomes in the 1st-line setting for a broad population of patients with HER2-positive metastatic breast cancer WILMINGTON, DE, USA J June 02, 2025 I Positive results from the DESTINY-Breast09 Phase III trial showed ENHERTU ® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to a taxane, trastuzumab and pertuzumab (THP) as a 1st-line treatment for patients with HER2-positive metastatic breast cancer. Results will be presented today during a special late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (abstract #LBA1008). In a prespecified interim analysis, ENHERTU plus pertuzumab reduced the risk of disease progression or death by 44% versus THP (based on a hazard ratio [HR] of 0.56; 95% confidence interval [CI] 0.44-0.71; p<0.00001). Median PFS was 40.7 months with ENHERTUplus pertuzumab compared to 26.9 months for THP, as assessed by blinded independent central review (BICR). The PFS benefit for ENHERTU plus pertuzumab versus THP was consistent across subgroups, including for the prespecified stratification factors of de novo or recurrent disease, hormone receptor status and PIK3CA mutation status. Investigator-assessed PFS demonstrated a median PFS of 40.7 months for ENHERTU plus pertuzumab compared to 20.7 months for THP (HR 0.49; 95% CI 0.39-0.61; nominal p-value <0.00001). Confirmed objective response rate (ORR) with ENHERTU plus pertuzumab was 85.1% versus 78.6% with THP. There were 58 complete responses (CRs) with ENHERTU plus pertuzumab compared to 33 with THP. Median duration of response (DOR) for ENHERTU plus pertuzumab exceeded three years (39.2 months) versus 26.4 months with THP. Overall survival (OS) was not mature at the time of the interim analysis (16% maturity at data cut-off); however, interim OS data showed an early trend favoring the ENHERTU combination compared to THP (HR 0.84; 95% CI 0.59-1.19). Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology, Dana-Farber Cancer Institute and principal investigator in the trial, said: “Patients with HER2-positive metastatic breast cancer often experience disease progression around two years after initiating standard-of-care first-line treatment. With a median progression-free survival of more than three years, the DESTINY-Breast09 results show trastuzumab deruxtecan combined with pertuzumab has the potential to become a new first-line standard of care for these patients.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Bringing ENHERTU earlier in the treatment of HER2-positive metastatic breast cancer may represent an important advancement for patients. The DESTINY-Breast09 trial showed the combination of ENHERTUand pertuzumab in the first-line setting substantially increased the amount of time before a patient’s cancer progressed compared to standard of care and nearly doubled the number of patients showing no signs of disease on imaging. Establishing a strong therapeutic response as soon as metastatic disease is diagnosed is critical given that about one in three patients do not receive further treatment after progressing in the first-line setting.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “ENHERTU continues to transform the treatment of metastatic breast cancer with the first new data in more than a decade to demonstrate improved outcomes for a broad population of patients with HER2-positive disease compared to THP in the first-line setting. DESTINY-Breast09 shows that initiating treatment with ENHERTU in combination with pertuzumab at the time of metastatic diagnosis can delay disease progression.” Summary of DESTINY-Breast09 interim analysis results Median duration of follow-up was nearly 2.5 years (29.2 months). As of the data cut-off, 302 (39.6%) patients remained on treatment, 174 in the ENHERTUplus pertuzumab arm and 128 in the THP arm. The safety profile of ENHERTU in combination with pertuzumab in DESTINY-Breast09 was consistent with the known profiles of each individual therapy with no new safety concerns identified. Interstitial lung disease (ILD)/pneumonitis occurred in 12.1% of patients treated with ENHERTU in combination with pertuzumab, as determined by an independent adjudication committee. The majority of ILD events were low Grade (Grade 1 [n=17; 4.5%] or Grade 2 [n=27; 7.1%]). There were no Grade 3 or Grade 4 ILD events. There were two Grade 5 (0.5%) ILD events in the ENHERTU plus pertuzumab arm. An additional investigational arm of the trial assessing ENHERTUmonotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis. ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. ENHERTU is already approved in more than 80 countries as 2nd-line treatment for patients with HER2-positive breast cancer based on the results from the DESTINY-Breast03trial. Indications and Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . Notes HER2-positive metastatic breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally. 1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer. 3 HER2 protein overexpression may occur as a result of HER2 gene amplification. 4 HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer. 5,6 Approximately 23,000 patientsare treated each year in the 1st-line HER2-positive setting across G7 countries alone. 7 While HER2-targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of 1st-line treatment with THP, which has been the standard of care for more than a decade. 4,8-10 Further, approximately one in three patients do not go on to receive treatment following 1st-line therapy due to disease progression or death. 11,12 DESTINY-Breast09 DESTINY-Breast09 is a global, multicenter, randomized, open-label, Phase III trial evaluating the efficacy and safety of ENHERTU(5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP (a taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab) as a 1st-line treatment in patients with HER2-positive metastatic breast cancer. Patients were randomized 1:1:1 to receive either ENHERTU monotherapy with a pertuzumab matching placebo; ENHERTU in combination with pertuzumab; or THP. Randomization was stratified by prior treatment ( de novo metastatic disease versus progression from early-stage disease), hormone receptor status and PIK3CA mutation status. The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the ENHERTU monotherapy and ENHERTU combination arms. Secondary endpoints include OS, ORR, DOR, investigator-assessed PFS and PFS2 and safety. DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov . ENHERTU ENHERTU is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. ENHERTU (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridization [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 ( ERBB2 ) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population. ENHERTU (5.4mg/kg) is approved in the US and other countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02 , DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US is contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU clinical development program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as monotherapy, in combination or sequentially with other anti-cancer therapies across multiple HER2-targetable cancers. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan-dlnk in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan-dlnk. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. With ENHERTU, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (MSD outside the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA -mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of datopotamab deruxtecan-dlnk alone and in combination with immunotherapy durvalumab. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca . References SOURCE: AstraZeneca