-One course of teplizumab delayed insulin dependence by approximately three years and improved beta cell function in at-risk (Stage 2) type 1 diabetes patients-
在高危(2期)1型糖尿病患者中，一个疗程的teplizumab可延迟胰岛素依赖约3年，并改善β细胞功能
RED BANK, N.J., March 3, 2021 /PRNewswire/ -- Provention Bio, Inc. (Nasdaq: PRVB), a biopharmaceutical company dedicated to intercepting and preventing immune-mediated disease, today announced that extended follow-up data from the pivotal "At-Risk" TN-10 Study were published in Science Translational Medicine. Results show that a single 14-day infusion course of teplizumab (PRV-031) delayed the onset of clinical disease and insulin dependence in at-risk type 1 diabetes (T1D) patients by approximately three years (median of 32.5 months), adding one year to previously reported results. The TN-10 Study was conducted through the Type 1 Diabetes TrialNet, an international research collaboration aimed at discovering ways to delay or prevent type 1 diabetes.
2013年3月3日讯/生物谷bioon /——Provention Bio公司(Nasdaq: PRVB)今天宣布，关键的“风险”TN-10研究的后续数据发表在《科学转化医学》(Science Translational Medicine)上。结果显示，teplizumab (PRV-031)单次14天输注疗程可将高危1型糖尿病(T1D)患者的临床疾病和胰岛素依赖的发生延迟约3年(中位数为32.5个月)，比此前报道的结果增加1年。TN-10研究是通过1型糖尿病TrialNet进行的，这是一个旨在发现延迟或预防1型糖尿病的方法的国际合作研究。
(PRNewsfoto/Provention Bio, Inc.)
(PRNewsfoto / Provention生物有限公司)
Teplizumab, Provention's lead drug candidate, is an anti-CD3 monoclonal antibody currently under review by the U.S. Food and Drug Administration (FDA) for the delay or prevention of clinical T1D in at-risk individuals, defined as having two or more T1D-related autoantibodies and dysglycemia (Stage 2 T1D). The lifetime risk of insulin-dependent clinical disease (Stage 3 T1D) approaches 100% in these pre-symptomatic Stage 2 patients.
Teplizumab是provenation的领先候选药物，是一种抗cd3单克隆抗体，目前正在美国食品和药物管理局(FDA)审查中，用于延迟或预防高危人群的临床T1D，定义为有两个或两个以上的T1D相关自身抗体和血糖异常(2期T1D)。在这些症状前2期患者中，胰岛素依赖性临床疾病(3期T1D)的终生风险接近100%。
"Teplizumab is the first disease-modifying investigational drug with data showing an ongoing delay to insulin-dependent T1D, now by approximately three years after a single course," said Dr. Kevan Herold, M.D., Professor of Immunology and Medicine at Yale University, lead author of the study. "These data build on existing clinical evidence demonstrating the potential for teplizumab to change the course of the disease and advance the treatment paradigm. We are continuing to observe patients in the TN-10 Study to determine whether the observed delay will extend even further over time."
该研究的主要作者、耶鲁大学免疫学和医学教授Kevan Herold博士说:“Teplizumab是第一个有数据显示持续延迟胰岛素依赖性T1D的疾病改变的临床研究药物，现在在一个疗程后大约延迟3年。”“这些数据建立在现有临床证据的基础上，证明了teplizumab改变疾病进程和推进治疗模式的潜力。我们将继续在TN-10研究中观察患者，以确定观察到的延迟是否会随着时间的推移进一步延长。”
The median time to clinical T1D was approximately 5 years in teplizumab-treated patients compared to slightly over 2 years in the placebo group. At this median follow-up of 2.5 years, twice as many teplizumab-treated patients remained free of clinical T1D compared to patients in the placebo group, 50% vs 22% respectively, (HR=0.457 p=0.01).
替普利单抗治疗组患者到临床T1D的中位时间约为5年，而安慰剂组患者的中位时间略大于2年。在这个2.5年的中位随访中，与安慰剂组相比，接受替普利单抗治疗的患者中有两倍的患者没有接受临床T1D治疗，分别为50%和22%，(HR=0.457 p=0.01)。
"It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high risk population for approximately three years versus placebo," said Frank Martin, Ph.D., JDRF Director of Research. "These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care."
JDRF研究主任Frank Martin博士说:“与安慰剂相比，单疗程teplizumab在高危人群中延迟胰岛素依赖约3年，这是非常令人鼓舞的。”“这些令人兴奋的结果是由TrialNet和Provention Bio坚定不移的努力实现的。Teplizumab如果获得FDA批准，可能会积极改变T1D风险人群的疾病发展进程和他们的护理标准。”
The following includes key additional data and analysis from the publication:Teplizumab treatment improved beta cell function, with an average on-study C-peptide AUC of 1.96 vs 1.68 pmol/ml, p=0.006.
以下包括来自该出版物的关键附加数据和分析:Teplizumab治疗改善了β细胞功能，研究中c肽平均AUC为1.96 vs 1.68 pmol/ml, p=0.006。
Initiation of teplizumab treatment reversed the decline in C-peptide levels while controls continued to decline (p=0.0015). The changes in C-peptide with teplizumab treatment were associated with increases in partially exhausted memory KLRG1+ TIGIT+ CD8+ T cells (r=0.44; p=0.014) that showed reduced secretion of IFN-gamma and TNF-alpha.
teplizumab治疗开始逆转了c肽水平的下降，而对照组继续下降(p=0.0015)。teplizumab治疗后c肽变化与部分耗尽记忆KLRG1+ TIGIT+ CD8+ T细胞增加相关(r=0.44;p=0.014)，显示ifn - γ和tnf - α分泌减少。
Total and early insulin secretory capacity was improved with teplizumab treatment suggesting improvement in beta cell glucose sensitivity reflecting normal beta cell function.
替普利珠单抗治疗可改善总的和早期胰岛素分泌能力，提示β细胞葡萄糖敏感性的改善反映了正常的β细胞功能。
Teplizumab was well tolerated, and the safety data is consistent with previous analyses.
Teplizumab耐受性良好，安全性数据与之前的分析一致。
"These data embolden our enthusiasm surrounding the potential impact teplizumab may have on the lives of T1D patients, families and caregivers," said Ashleigh Palmer, CEO and Co-Founder, Provention Bio. "Outcomes such as these validate Provention's mission to intercept and prevent debilitating and life-threatening diseases. We continue working closely with the FDA in their review of our BLA submission for teplizumab. The PDUFA goal date is July 2, 2021."
Provention Bio首席执行官兼联合创始人Ashleigh Palmer表示:“这些数据鼓舞了我们对teplizumab可能对T1D患者、家庭和护理人员的生活产生的潜在影响的热情。”“这些结果验证了Provention拦截和预防使人衰弱和危及生命的疾病的使命。我们将继续与FDA密切合作，对我们的BLA申请teplizumab进行审核。PDUFA的目标日期是2021年7月2日。”
About the Pivotal "At-Risk" TN-10 Study:The "At-Risk" TN-10 Study, a pivotal Phase 2 clinical trial, evaluated teplizumab for the delay of insulin-dependent type 1 diabetes (Stage 3 of clinical T1D) in presymptomatic, Stage 2 or at-risk patients, defined by the presence of two or more T1D-related autoantibodies and dysglycemia. Seventy-six patients were enrolled ages 8 to 49, with 72% under the age of 18, and randomized to receive a single course of either teplizumab or placebo. Patients were followed in a blinded fashion until 40 of them developed clinical-stage T1D, and then indefinitely after the analysis of the randomized period data.
对关键的“高危”TN-10研究:“高危”TN-10研究中,一个关键的2期临床试验,评估teplizumab延迟胰岛素依赖型的1型糖尿病发生前症状临床内转(阶段3),第二阶段或高危患者,由两个或两个以上的存在T1D-related自身抗体和糖代谢。76名年龄在8 - 49岁的患者被纳入研究，其中72%年龄在18岁以下，随机接受单疗程替普利单抗或安慰剂治疗。对患者进行盲法随访，直到其中40人发展为临床T1D期，然后在随机期数据分析后无限期随访。
The study was conducted by TrialNet, a network of the world's leading T1D researchers, and funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and JDRF. The primary results were published in the New England Journal of Medicine and simultaneously presented at the 2019 American Diabetes Association's 79th Scientific Sessions.
该研究由TrialNet进行，TrialNet是世界领先的T1D研究人员网络，由美国国家糖尿病、消化和肾脏疾病研究所(NIDDK)和JDRF资助。主要研究结果发表在《新英格兰医学杂志》上，并同时在2019年美国糖尿病协会第79届科学会议上发表。
About Type 1 Diabetes (T1D):Over 1.6 million Americans have type 1 diabetes (T1D), an autoimmune disease caused by the destruction of beta cells. T1D symptoms can take months or years to develop. The psychological impact of T1D is hard to quantity, but a diagnosis is life-altering, and regular monitoring and maintenance can be extremely stressful. T1D typically takes more than a decade off a person's life and life expectancy is reduced by 16 years on average for people diagnosed with T1D before the age of 10. Insulin is the current T1D treatment. It is necessary to keep patients alive, but it is a constant effort for patients. No disease-modifying treatments for T1D are currently available.
关于1型糖尿病(T1D):超过160万美国人患有1型糖尿病(T1D)，这是一种由细胞破坏引起的自身免疫性疾病。T1D症状可能需要几个月或几年的时间发展。T1D的心理影响很难量化，但诊断结果会改变生活，定期监测和维护可能会带来极大的压力。T1D通常会缩短一个人10年以上的寿命，在10岁之前被诊断为T1D的人的平均预期寿命会缩短16年。胰岛素是目前T1D的治疗方法。维持病人的生命固然必要，但对病人来说却是一种不断的努力。目前还没有治疗T1D疾病的治疗方法。
About Teplizumab (PRV-031):
Teplizumab(减压阀- 031):
Teplizumab is an investigational anti-CD3 monoclonal antibody (mAb) with a filed Biologics License Application (BLA) under Priority Review by the U.S. Food and Drug Administration (FDA) for the delay or prevention of clinical type 1 diabetes (T1D) in at-risk individuals. More than 800 patients have received teplizumab in multiple clinical studies involving more than 1,000 subjects. In previous studies of newly diagnosed patients, teplizumab consistently demonstrated the ability to preserve beta-cell function, a measure of endogenous insulin production. It correspondingly reduced the need for exogenous insulin use. Teplizumab has been granted Breakthrough Therapy Designation by the FDA and PRIME designation by the European Medicines Administration. Provention is currently also evaluating teplizumab in patients with newly diagnosed insulin-dependent T1D (the Phase 3 PROTECT study).
Teplizumab是一种实验性抗cd3单克隆抗体(mAb)，目前已提交生物制品许可申请(BLA)，正在接受美国食品和药物管理局(FDA)的优先审查，用于延迟或预防高危人群的临床1型糖尿病(T1D)。在涉及1000多名受试者的多项临床研究中，超过800名患者接受了teplizumab治疗。在之前对新诊断的患者的研究中，teplizumab一致证明了保持细胞功能的能力，内源性胰岛素生产的测量。相应地减少了外源性胰岛素的使用。Teplizumab已被FDA授予突破性治疗指定，被欧洲药品管理局授予主要指定。teplizumab的预防目前也在评估新诊断的胰岛素依赖型T1D患者(3期PROTECT研究)。