A novel diagnostic Kit for Hepatocellular Carcinoma

项目总结 ImCare Biotech正在寻求将Seravue®商业化，这是一种基于ELISA的诊断系统，能够 对早期和晚期肝细胞癌的诊断具有较高的敏感性和特异性。有了NCI- 支持第一阶段和第二阶段的SBIR奖励以及内部和外部投资者的支持，ImCare完成了 Seravue®产品的技术开发，现在请求阶段IIB SBIR支持进行 510(K)申请和随后的监管批准所需的前瞻性临床研究。商业化 Seravue®的应用有可能显著改善接受肝移植患者的肝细胞癌的早期检测 由于高危情况进行监测，从而确保及时、有效的治疗和极大地 提高存活率。肝癌是最常见和最致命的一种肝癌，其5年存活率为 不到15%，每年直接造成全球数十万人死亡。肝细胞癌是 通常在治疗基本无效的晚期诊断，导致较差的预后，但 早期诊断和治疗可以将5年存活率提高到70%。因此，已知的处于高潮的个人 肝癌的风险--包括患有肝硬变或慢性乙肝/丙型肝炎的患者--每隔3年接受一次肝细胞癌监测 到6个月，以提高及早发现疾病的机会。目前的监测方法具有重大意义 缺点包括成本、负担、对早期疾病的较差检测以及敏感性和特异性不足。至 为了满足对更好监控工具的需求，我们开发了Seravue®，这是一种微创、准确、 一致且廉价的肝癌检测-丝氨酸蛋白酶抑制剂Kazal(LC-Spik)，一种蛋白质 由肝细胞癌细胞特异性分泌。在第一阶段和第二阶段研究中，ImCare证实了 Seravue®：1)它将肝癌与其他肝病、非肝病和健康人区分开来；2)它 明显比甲胎蛋白(AFP)更敏感和特异，甲胎蛋白是最常见的 肝细胞癌。在这个IIB阶段SBIR中，ImCare建议进行一项临床研究，以支持510(K)计划的申请 批准将Seravue®列为II类医疗设备。目标1.论证使用的可行性和有效性 血清LC-SPIK水平评估慢性肝病患者发生肝细胞癌的风险。根据FDA 指导下，血液生物标记物DCP将被用作主谓词。主端点：敏感度和 与DCP相比，特异性更强。次要终点：与DCP相比，计算发生肝细胞癌的相对风险。 目标2.寻求CMS报销并提交510(K)申请。里程碑：1)以下方面的额外要求 确认CMS报销并提交2)510(K)申请。影响：成功完成这些里程碑 预计将支持FDA批准Seravue®，这将提供早期检测和监测工具 对于肝细胞癌来说，这比目前的工具提供了更好的疗效，更低的成本和更低的负担。商业化的 预计Seravue®将通过增加早期检测来拯救生命。

PROJECT SUMMARY ImCare Biotech is seeking to commercialize Seravue®, an ELISA-based diagnostic system that is able to identify both early and late stage Hepatocellular Carcinoma (HCC) with high sensitivity and specificity. With NCI- supported Phase I and II SBIR awards plus internal and external investor support, ImCare completed the technical development of the Seravue® product and now requests Phase IIB SBIR support to conduct a prospective clinical study required for a 510(k) filing and subsequent regulatory clearance. Commercialization of Seravue® has the potential to substantially improve early detection of HCC in patients undergoing surveillance due to high-risk conditions, thereby ensuring timely, effective treatment and greatly increasing survival. HCC, the most common and deadliest form of liver cancer, has a 5-year survival rate of less than 15% and is directly responsible for hundreds of thousands of deaths worldwide each year. HCC is typically diagnosed at a late stage when treatments are largely ineffective, resulting in poorer prognosis, but early diagnosis and treatment can increase 5-year survival rates to >70%. Thus, individuals known to be at high risk for HCC—including patients with liver cirrhosis or chronic hepatitis B/C—undergo HCC surveillance every 3 to 6 months to improve the chances of catching the disease early. Current surveillance methods have significant drawbacks including cost, burden, poor detection of early disease, and inadequate sensitivity and specificity. To address the need for a better surveillance tool, we developed Seravue®, a minimally-invasive, accurate, consistent, and inexpensive test for Liver Cancer-Serine Protease Inhibitor Kazal (LC-SPIK), a protein specifically secreted by HCC cells. In Phase I and Phase II studies, ImCare confirmed two critical features of Seravue®: 1) It distinguishes HCC from other liver diseases, non-liver diseases, and healthy subjects and 2) it is significantly more sensitive and specific than alpha fetoprotein (AFP), the most common biomarker test for HCC. In this Phase IIB SBIR, ImCare proposes to conduct a clinical study to support a 510(k) filing for the clearance of Seravue® as class II medical device. Aim 1. Demonstrate the feasibility and effectiveness of using serum levels of LC-SPIK to assess the risk of developing HCC for patients with chronic liver disease. Per FDA guidance, the blood biomarker DCP will be used as the primary predicate. Primary Endpoints: Sensitivity and specificity compared to DCP. Secondary Endpoint: Calculated relative risk of developing HCC compared to DCP. Aim 2. Pursue CMS reimbursement and submit a 510(k) application. Milestones: 1) Additional requirements for CMS reimbursement identified and 2) 510(k) filing submitted. Impact: Successful completion of these milestones is expected to support FDA clearance of Seravue®, which will provide an early detection and surveillance tool for HCC that provides better efficacy, lower cost, and lower burden than current tools. Commercialization of Seravue® is expected to save lives by increasing early detection.