The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advances over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the first quarter of 2021.
There are more than 27,000 new cases of gastric cancer in the US each year, of which approximately one in five are HER2 positive.
For patients with metastatic gastric cancer who progress on initial treatment with an anti-HER2 medicine, there are no other approved HER2-directed medicines.
José Baselga, Executive Vice President, Oncology R&D, said: “Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are no approved HER2-directed medicines. The prognosis for these patients is poor, as available treatment options offer only limited clinical benefit. This milestone brings us one step closer to delivering a potentially practice-changing medicine to patients with gastric cancer in the US.”
Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: “The results of the DESTINY-Gastric01 trial are unprecedented as they represent the first time a HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting. Building on the recent Breakthrough Therapy Designation, the filing of the application and Priority Review by the FDA for this potential new indication for ENHERTU reflects the importance of the data and the significant unmet need for patients with previously treated HER2-positive metastatic gastric cancer.”
The sBLA is based on results from the DESTINY-Gastric01 randomized Phase II trial, which demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the primary endpoint, and overall survival (OS), a key secondary endpoint, for patients treated with ENHERTU versus chemotherapy (paclitaxel or irinotecan monotherapy).
The safety and tolerability profiles of ENHERTU in DESTINY-Gastric01 were consistent with that observed in the gastric cancer cohort of the Phase I trial and previously reported ENHERTU trials in other tumors.3 The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count, anemia, decreased white blood cell count and decreased appetite. There were 12 (9.6%) cases of confirmed treatment-related interstitial lung disease (ILD) or pneumonitis in 125 patients treated with ENHERTU as determined by an independent review committee. The majority of cases were Grade 1 or 2 with two Grade 3, one Grade 4 and no Grade 5 (ILD-related deaths).
The results from the trial were presented during the American Society of Clinical Oncology ASCO20 Virtual Scientific Program and simultaneously published online in The New England Journal of Medicine in May 2020.
ENHERTU received Breakthrough Therapy Designation from the US FDA in May 2020 for patients with unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received two or more prior regimens including trastuzumab and Orphan Drug Designation for patients with gastric cancer, including GEJ adenocarcinoma. ENHERTU has not been approved in the US for gastric or GEJ adenocarcinoma.
FDA-Approved Indication for ENHERTU
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Source: Company Press Release