FDA Grants Orphan Drug Designation to Certepetide for Cholangiocarcinoma
核心洞察
The FDA has granted orphan drug designation to certepetide for the treatment of cholangiocarcinoma (搜索), a rare and aggressive cancer with limited treatment options.
Certepetide is currently being evaluated in the phase 2 BOLSTER trial in combination with standard-of-care therapies for first- and second-line cholangiocarcinoma (搜索).
The orphan drug designation provides Lisata Therapeutics with potential benefits, including market exclusivity, exemption from user fees, and tax credits for clinical trials.
Lisata Therapeutics' certepetide, formerly known as LSTA1, has received orphan drug designation from the FDA for the treatment of cholangiocarcinoma (搜索). This designation highlights the potential of certepetide to address the unmet needs in treating this rare and aggressive cancer. The drug is currently under evaluation in the phase 2 BOLSTER trial (NCT05712356).
Certepetide's Mechanism of Action
Certepetide is a cyclic peptide designed to enhance the delivery of anticancer agents into solid tumors. It operates by activating the C-end rule active transport mechanism within tumor cells, which facilitates the penetration and accumulation of covalently bound anticancer agents. Preclinical data suggest that certepetide can improve the efficacy of chemotherapies, immunotherapies, and RNA-based agents, as well as modulate the tumor microenvironment to boost immune responses. Clinical trials have indicated that adding certepetide to chemotherapy regimens results in favorable safety, tolerability, and improved chemotherapy activity.
BOLSTER Trial Details
The BOLSTER trial is a double-blind, placebo-controlled, multi-center, randomized study assessing the addition of certepetide to gemcitabine, cisplatin, and durvalumab (Imfinzi) versus standard of care alone in patients with cholangiocarcinoma (搜索) and other solid tumors. The trial includes both first- and second-line treatment cohorts. Patients eligible for the trial must have confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma without prior systemic chemotherapy, targeted therapy, or loco-regional therapy. Patients with recurrent disease more than 6 months after adjuvant chemotherapy are also eligible. Key inclusion criteria also include an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and measurable lesions per RECIST 1.1 criteria.
The first-line cohort receives 1500 mg of intravenous (IV) durvalumab every 21 days, along with 25 mg/m² of IV cisplatin and 1000 mg/m² of IV gemcitabine on days 1 and 8 every 21 days for 8 cycles, followed by every 28 days for additional cycles. The second-line cohort receives FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) every 14 days. Both cohorts are administered either placebo or 3.2 mg/kg of IV certepetide as a slow push over 1 minute. The primary endpoint of the study is the incidence of adverse effects.
Significance of Orphan Drug Designation
The FDA's orphan drug designation is granted to therapies intended to treat rare diseases or conditions affecting fewer than 200,000 people in the U.S. This designation provides Lisata Therapeutics with potential benefits, including up to 7 years of market exclusivity, exemption from user fees, and tax credits for qualified clinical trials. According to Kristen K. Buck, MD, executive vice president of Research and Development and chief medical officer of Lisata, this designation is a pivotal step toward addressing the unmet need for cholangiocarcinoma (搜索) therapies.
Certepetide's Development in Other Cancers
Certepetide has previously been granted orphan drug designation for malignant glioma (搜索) and osteosarcoma (搜索) by the FDA, and for pancreatic cancer (搜索) by the European Medicines Agency. It has also received fast track designation from the FDA for pancreatic cancer. Ongoing investigations are evaluating certepetide in combination regimens for solid tumors, including metastatic pancreatic ductal adenocarcinoma (PDAC), colon cancer, appendiceal cancer, and glioblastoma multiforme. These include the phase 2 ASCEND trial (NCT05042128) and the phase 1b/2 CENDIFOX trial (NCT05121038).