ST-246 treatment of smallpox vaccine-related adverse events

ST-246治疗天花疫苗相关不良事件

基本信息

批准号：
8126456
负责人：
Douglas W. Grosenbach
金额：
$ 100万
依托单位：
SIGA TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2013-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Naturally occurring smallpox has been eradicated but remains a credible threat to the security of the United States due to its potential use as an agent of terror or biowarfare. Given that approximately 25% of the population is contraindicated to receive the vaccine due to direct risk of adverse events or the possibility of placing direct contacts at risk (23), the current smallpox vaccine is inadequate to protect the US population from smallpox. SIGA Technologies (SIGA) is currently conducting NDA-enabling activities seeking FDA approval for ST-246 as a post-exposure therapeutic for smallpox. SIGA is seeking to expand ST-246 indications for use to include it as an adjunct to smallpox vaccination to prevent or treat adverse events due to the vaccine. We and our collaborators have demonstrated in more than 30 animal studies that ST-246 is safe and very effective for the prevention or treatment of orthopoxvirus infection, including variola, the causative agent of smallpox. This suggested to us that ST-246 might also be used to prevent or treat adverse events due to the smallpox vaccine, a live vaccinia virus closely related to variola. We have demonstrated in immunocompetent mice (14) and monkeys that reactogenicity to the vaccine is reduced while protective immunity elicited by the vaccine is not affected. Further, in our Phase I studies, as reported in the Progress Report below, we have determined that ST-246 provides full protection from lethal poxvirus challenge in numerous murine models of immunodeficiency and that immunodeficient mice may be safely vaccinated if treated with ST-246 as an adjunct to the vaccine. Immunodeficient mice that are safely vaccinated are subsequently resistant to lethal challenge suggesting that remaining components of the immune system are able to mediate protection. ST-246 is a promising candidate for inclusion in the Strategic National Stockpile as a component of the Smallpox Response Plan to 1) provide protection from smallpox if an individual is exposed and 2) reduce the occurrence of adverse events due to vaccination. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to advance ST-246 development as an adjunct to the smallpox vaccine through the pre-clinical development phase so that an Investigational New Drug (IND) application may be filed with the Food and Drug Administration upon completion of the proposed studies.

描述（由申请人提供）：自然发生的天花已经被根除，但由于其潜在用作恐怖或生物贸易的代理人而对美国的安全仍然是可信的威胁。鉴于由于直接发生不良事件的直接风险或将直接接触面临风险的可能性（23）而被禁忌接受疫苗，因此当前的天花疫苗不足以保护美国人口免受天花的侵害。 SIGA Technologies（SIGA）目前正在开展实施NDA的活动，以寻求FDA批准ST-246作为天花后暴露后治疗。 Siga正在寻求扩大ST-246的指示，以将其作为天花疫苗接种的辅助，以防止或治疗由于疫苗而导致的不良事件。我们和我们的合作者在30多项动物研究中证明了ST-246是安全且对预防或治疗正托病毒感染的安全性和有效性，包括天花的病因，包括Variola。这向我们表明，由于天花疫苗，ST-246也可以用于预防或治疗不良事件，这是一种与Variola密切相关的活疫苗病毒。我们已经在免疫能力的小鼠（14）中证明了与疫苗的反应生成性，而疫苗引起的保护性免疫不受影响。此外，在下面的进度报告中报道的那样，在我们的第一阶段研究中，我们确定ST-246在许多免疫缺陷的鼠模型中提供了完全保护致命的痘病毒挑战，并且如果用ST-246作为疫苗的辅助手术，则可以安全接种免疫缺陷的小鼠，如果用ST-246进行疫苗接种。安全接种疫苗的免疫缺陷小鼠随后对致命挑战具有抵抗力，这表明免疫系统的其余成分能够介导保护。 ST-246是一名有前途的候选人，将其纳入战略性国家储备作为天花响应计划的组成部分，以便1）如果个人暴露并2）减少因疫苗接种而导致不良事件的情况。公共卫生相关性：该提案的目的是通过临床前开发阶段推进ST-246的开发，作为天花疫苗的辅助，以便在拟议的研究完成后，可以向食品药品监督管理局提出研究新药（IND）的应用。