Enfortumab vedotin
- Generic Name
- Enfortumab vedotin
- Brand Names
- Padcev
- Drug Type
- Biotech
- CAS Number
- 1346452-25-2
- Unique Ingredient Identifier
- DLE8519RWM
- Background
Enfortumab vedotin is an antibody-drug conjugate used in the treatment of patients with advanced, treatment-resistant urothelial cancers. It is comprised of a fully human monoclonal antibody targeted against Nectin-4 and a microtubule-disrupting chemotherapeutic agent, monomethyl auristatin E (MMAE), joined by a protease-cleavable link. It is similar to brentuximab vedotin, another antibody conjugated with MMAE that targets CD-30 instead of Nectin-4.
The clinical development of enfortumab vedotin was the result of a collaboration between Astellas Pharma and Seattle Genetics and it was first approved for use in the United States in December 2019 under the brand name Padcev. Enfortumab vedotin was later approved by the European Commission on April 13, 2022.
- Indication
Enfortumab vedotin is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting. Enfortumab vedotin can also be indicated in combination with pembrolizumab in adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy under accelerated approval from the FDA.
- Associated Conditions
- Locally Advanced Urothelial Cancer, Locally Advanced or Metastatic Urothelial Carcinoma (UC), Metastatic Urothelial Cancer
Astellas to Present New Long-Term Survival Data for Cancer Therapies at ASCO 2025
• Astellas will showcase 16 abstracts at the 2025 ASCO Annual Meeting, including two oral presentations highlighting long-term survival data for its oncology portfolio.
• New post-hoc analyses will feature five-year overall survival data for XTANDI (enzalutamide) in metastatic hormone-sensitive prostate cancer and exploratory analyses for PADCEV (enfortumab vedotin) in urothelial cancer.
• The presentations underscore Astellas' commitment to delivering meaningful clinical outcomes for patients with advanced prostate and bladder cancers through innovative treatment approaches.
Merck and Daiichi Sankyo Launch Phase 3 Trial of Novel B7-H3 Targeted ADC for Advanced Esophageal Cancer
• The IDeate-Esophageal01 Phase 3 trial has begun evaluating ifinatamab deruxtecan, a potential first-in-class B7-H3 directed antibody-drug conjugate, against standard chemotherapy in advanced esophageal squamous cell carcinoma.
• Esophageal squamous cell carcinoma accounts for 90% of global esophageal cancers with dismal survival rates of 15-20%, highlighting the urgent need for new treatment approaches after first-line therapy failure.
• The trial follows promising early-phase results and will enroll approximately 510 patients across Asia, Europe, and North America, with overall survival as the primary endpoint.
Pfizer to Showcase Breakthrough Cancer Therapies at ASCO 2025 with Over 60 Presentations
• Pfizer will present data from more than 60 abstracts at ASCO 2025, including 15 oral presentations highlighting advancements across breast, genitourinary, hematologic, thoracic, and colorectal cancers.
• Two late-breaking presentations will be featured in ASCO's press program, including pivotal survival data for BRAFTOVI in colorectal cancer and progression-free survival results for vepdegestrant in metastatic breast cancer.
• The company will showcase novel antibody-drug conjugate combinations with immunotherapy and present five-year survival data for XTANDI in prostate cancer, supporting Pfizer's goal of delivering eight breakthrough cancer medicines by 2030.
Pharmaceutical Industry Braces for $236 Billion Patent Cliff by 2030: Strategic Responses from Major Players
• The global pharmaceutical industry faces a $236 billion patent cliff between 2025-2030, with nearly 70 blockbuster drugs losing exclusivity and exposing major companies to significant revenue losses.
• Key drugs approaching patent expiration include Merck's Keytruda ($25B), Bristol-Myers Squibb's Eliquis ($12B), and Johnson & Johnson's Stelara ($10.9B), forcing companies to rapidly adapt through pipeline diversification and cost-cutting measures.
• Companies are responding with increased M&A activity, AI-driven R&D efficiency, and strategic pivots to high-growth therapeutic areas, while the cliff will likely improve drug affordability but potentially slow innovation.
Seagen Wins $42M Patent Verdict Against Daiichi Sankyo Over Enhertu Breast Cancer Drug
• A US jury ruled that Daiichi Sankyo and AstraZeneca's breast cancer drug Enhertu infringes Seagen's patent, resulting in a $42 million damages award for past royalties.
• The disputed patent covers antibody-drug conjugate technology using auristatin compounds, with the jury finding willful infringement in Enhertu's design and manufacture.
• The verdict could have significant financial implications as Enhertu's sales doubled last year to $426 million, with potential expansion into HER2-low breast cancer representing a $3 billion opportunity.
Summit and Pfizer Partner to Evaluate Novel Cancer Therapy Combinations with Ivonescimab
• Summit Therapeutics and Pfizer have established a clinical trial collaboration to test ivonescimab, a PD-1/VEGF bispecific antibody, in combination with Pfizer's antibody drug conjugates for multiple solid tumors.
• The partnership aims to accelerate development opportunities by evaluating ivonescimab with several vedotin-based ADCs, with clinical trials scheduled to begin mid-2025.
• Over 2,300 patients have already received ivonescimab in global clinical studies, with the drug showing promising potential through its unique tetravalent structure and cooperative binding mechanism.
Avelumab Maintenance Shows Consistent Survival Benefits in Advanced Urothelial Cancer Patients With and Without Diabetes
• Phase 3 JAVELIN Bladder 100 trial demonstrates avelumab maintenance therapy significantly extended overall survival to 20.8 months versus 14.5 months with best supportive care alone in diabetic patients with advanced urothelial carcinoma.
• The treatment showed similar efficacy in non-diabetic patients, with median overall survival of 24.7 months compared to 15.8 months with best supportive care, confirming benefit regardless of diabetes status.
• Safety profile remained consistent across both patient groups, with manageable immune-related adverse events occurring in approximately 32% of avelumab-treated patients.
Phase II Trial Shows Breakthrough 63.6% Response Rate for Novel Bladder Cancer Combination Therapy
• Disitamab Vedotin combined with Toripalimab achieved a 63.6% pathological complete response rate in muscle-invasive bladder cancer patients, nearly doubling traditional chemotherapy outcomes.
• The clinical trial demonstrated strong efficacy across all HER2 expression levels, with HER2 IHC 3+ patients showing an exceptional 84.6% complete response rate.
• The treatment showed favorable safety with only 27.7% grade 3 or higher adverse events, significantly lower than conventional chemotherapy's 40-50% rate.
Enfortumab Vedotin Shows Promise for Upper Tract Urothelial Cancer Patients Ineligible for Standard Treatment
• A retrospective analysis reveals enfortumab vedotin, alone or combined with pembrolizumab, achieved a 36.4% objective response rate in upper tract urothelial cancer patients.
• The study demonstrated a notable 72.3% disease control rate among 22 patients, with 81.8% having visceral metastases at baseline.
• This treatment approach offers potential hope for patients typically excluded from traditional urothelial cancer trials due to cisplatin ineligibility.
Enfortumab Vedotin Shows Manageable Safety Profile in Ultra-Elderly Urothelial Cancer Patients
• A retrospective study of 26 ultra-elderly patients with urothelial carcinoma demonstrated that enfortumab vedotin had manageable toxicity, with no grade 4/5 adverse events reported.
• Upfront dose reduction was more common in patients aged 85 and older, with lower starting doses associated with fewer grade 2/3 treatment-related adverse events.
• The study included patients receiving either enfortumab vedotin monotherapy (69.2%) or combination therapy with pembrolizumab (30.8%), with a median treatment duration of 19.5 weeks.
Adverse Events Linked to Better Survival Outcomes in Enfortumab Vedotin Treatment for Urothelial Cancer
• New research reveals patients experiencing neuropathy, skin rash, or hyperglycemia while taking Enfortumab Vedotin showed significantly improved progression-free survival in metastatic urothelial carcinoma treatment.
• Study of 83 patients demonstrated extended progression-free survival of up to 15.9 months in those experiencing specific adverse events, compared to 4.5 months in those without these effects.
• Findings were presented at the 2025 ASCO Genitourinary Cancers Symposium, following the FDA's recent approval of Enfortumab Vedotin with Pembrolizumab for advanced urothelial cancer.
PADCEV-KEYTRUDA Combination Shows Sustained Survival Benefit in Advanced Urothelial Cancer Trial
• Phase 3 EV-302 trial demonstrates PADCEV plus KEYTRUDA reduces mortality risk by 49% compared to chemotherapy in advanced urothelial cancer patients, with median overall survival of 33.8 months versus 15.9 months.
• The combination therapy showed significant progression-free survival benefit of 12.5 months compared to 6.3 months with chemotherapy, representing a 52% reduction in disease progression risk.
• Extended 12-month follow-up data confirms sustained efficacy across all patient subgroups, including both cisplatin eligible and ineligible patients, with no new safety concerns identified.
Tisotumab Vedotin Demonstrates Survival Benefit in Chinese Cervical Cancer Subpopulation
• Tisotumab vedotin significantly improved overall survival compared to chemotherapy in Chinese patients with previously treated recurrent or metastatic cervical cancer.
• The antibody-drug conjugate reduced the risk of death by 45% in the Chinese subpopulation, consistent with global trial results.
• Zai Lab plans to submit a new drug application to China's National Medical Products Administration based on these findings.
• The results offer hope for addressing the unmet need for effective treatments after relapse, including after anti-PD-(L)1 therapy.
J&J Seeks FDA Approval for TAR-200 in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer
• Johnson & Johnson has initiated a New Drug Application (NDA) submission to the FDA for TAR-200.
• TAR-200 is intended for patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC).
• Phase 2b SunRISe-1 study data showed an 83.5% complete response rate with TAR-200 monotherapy.
• The FDA is reviewing the application under the Real-Time Oncology Review (RTOR) program to expedite potential approval.
FDA Approves Seattle Genetics' Advanced Breast Cancer Drug Tukysa
The FDA has granted early approval to Seattle Genetics' breast cancer drug Tukysa (tucatinib) for advanced HER2-positive breast cancer, including cases with brain metastases, marking the company's first approval in breast cancer treatment.
Emerging Intravesical and Systemic Therapies Revolutionize Bladder Cancer Treatment
• Intravesical therapies like cretostimogene and TAR-200 show promising complete response rates in BCG-unresponsive NMIBC, but duration of response remains a key factor.
• Perioperative systemic therapies, including neoadjuvant chemo-immunotherapy with durvalumab, aim to improve event-free and overall survival in muscle-invasive urothelial carcinoma.
• Antibody-drug conjugates (ADCs) targeting Nectin-4 and HER2, such as enfortumab vedotin and disitamab vedotin, demonstrate significant potential in metastatic urothelial cancer.
• Novel strategies, including dual-targeting antibodies and combinations of ADCs with immunotherapies, are being explored to further enhance treatment efficacy and overcome resistance.
DATROWAY® (Datopotamab Deruxtecan) Receives EU Approval for Previously Treated Metastatic HR+/HER2- Breast Cancer
• DATROWAY, a TROP2-directed antibody drug conjugate (ADC), has been approved in the European Union for treating adult patients with unresectable or metastatic HR+/HER2- breast cancer who have received endocrine therapy and at least one line of chemotherapy.
• The approval is based on the TROPION-Breast01 phase 3 trial, which showed DATROWAY reduced the risk of disease progression or death by 37% compared to chemotherapy, with a median PFS of 6.9 months versus 4.9 months.
• This marks the second ADC approved for breast cancer based on Daiichi Sankyo's DXd technology and the third medicine from their oncology pipeline to receive EU approval, highlighting their commitment to developing innovative cancer treatments.
Radiopharmaceutical Antibody-Drug Conjugates (rADCs) Emerge as Promising Cancer Therapies
• rADCs are designed to deliver radiation directly to cancer cells, minimizing side effects compared to traditional radiation therapy.
• Several companies are developing rADCs with various radioisotopes and antibodies, targeting cancers like prostate, breast, and lung cancer.
• Clinical trials are underway to assess the efficacy and safety of rADCs, showing promising results in reducing tumor markers like PSA.
• Challenges remain in supply chain logistics, dosimetry, and optimizing drug delivery to target tissues for effective cancer treatment.
Seagen Secures $2.6B Deal with RemeGen for Novel HER2-Targeting Cancer Drug
• Seagen has acquired ex-Asian rights to RemeGen's disitamab vedotin for $200 million upfront, with potential payments of $2.4 billion, targeting HER2-positive cancers including breast, bladder, and gastric tumors.
• The antibody-drug conjugate has already received conditional approval in China for HER2-positive gastric cancer and breakthrough designation from FDA for bladder cancer.
• The deal positions Seagen to compete with established HER2-targeting ADCs like AstraZeneca/Daiichi Sankyo's Enhertu and Roche's Kadcyla, while focusing initially on distinct market segments.
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