Iterum Therapeutics, Inc.

Taylor Tieden for BioSpace The FDA is looking at four events for the remainder of October, one of which is an advisory committee meeting for a dual SGLT inhibitor for use alongside insulin in type 1 diabetes and chronic kidney disease. This month seems to be a relatively slow one for the FDA, which has only a handful of catalysts coming up, including target action dates for a KRAS inhibitor and a UTI drug. Read below for more. Amgen Seeks Colorectal Cancer Approval for Lumakras By October 17, the FDA is expected to release its decision on Amgen ’s application for Lumakras (sotorasib) in combination with Vectibix (panitumumab) for the treatment of metastatic colorectal cancer. The application is backed by the CodeBreaK 300 study, which tested the combination regimen against the investigator’s choice of therapy. A total of 160 patients were enrolled into the study, according to its clinicaltrials.gov page , all of whom carried the KRAS G12C mutation. The FDA gave Amgen’s application its Priority Review designation. In August 2023, Amgen announced that Lumakras plus Vectibix aced the primary endpoint in CodeBreak 300, demonstrating a significant improvement in progression-free survival versus current standard of care. Additional data from the study were reported at the 2024 American Society of Clinical Oncology annual meeting in June, showing a trend toward better overall survival in patients treated with Amgen’s drug combo. Lumakras is a small molecule inhibitor of G12C-mutated KRAS , which is involved in the hyperactive cell division seen in cancer. It keeps mutated KRAS in an inactive state and helps prevent unchecked tumor growth while also prompting cell death. The drug was first approved for non-small cell lung cancer under the FDA’s accelerated pathway in May 2021, but its full approval was denied in December 2023 , with the regulator asking for an additional confirmatory study. Camurus Proposes Subcutaneous Octreotide for Acromegaly Swedish biotech Camurus is seeking approval for its investigational subcutaneous injection of octreotide for the once-monthly treatment of acromegaly, a hormonal disorder that causes abnormal bone and tissue growth. The FDA has until October 21 to release its verdict . Octreotide is a peptide drug that has long been approved for acromegaly. Bynfezia Pen (octreotide acetate), for instance, was approved for subcutaneous treatment in 1988 and is also indicated for other diseases, such as diarrhea associated with metastatic carcinoid tumors or vasoactive intestinal peptide tumors. According to Bynfezia’s label , octreotide works by mimicking the effects of the natural hormone somatostatin, exerting a strong inhibitory effect on other hormones, such as glucagon and insulin. Octreotide also blocks the action of growth hormone, which in acromegaly is present in high amounts. Camurus’ subcutaneous formulation of octreotide, dubbed CAM2029, allows for better exposure to the drug and enables a more convenient once-monthly dosing schedule. Bynfezia, by comparison, is given three times a day for acromegaly. CAM2029 also comes as a pre-filled injection pen to allow self-administration. The drug application is backed by the Phase III ACROINNOVA 2 study, which enrolled 135 patients who either had biochemically controlled disease or who had uncontrolled disease but were on stable doses of standard-of-care therapy. Results showed that CAM2029 led to better biochemical control of acromegaly versus standard of care, alongside improvements in symptom burden and quality of life. Iterum Advances Oral UTI Drug for Women The FDA is reviewing Iterum Therapeutics’ New Drug Application (NDA) for sulopenem etzadroxil/probenecid, also called oral sulopenem, for the treatment of uncomplicated urinary tract infection (uUTI) in women. The regulator is expected to release its verdict by October 25. Oral sulopenem is backed by findings from the Phase III REASSURE study. According to a topline readout in January 2024, oral sulopenem matched oral Augmentin (amoxicillin/clavulanate) in terms of overall response, the study’s primary endpoint. Additionally, overall success, which takes into account clinical and microbiological outcomes, was statistically better in the oral sulopenem group than in Augmentin comparators. Last month, the FDA’s Antimicrobial Drugs Advisory Committee met to discuss Iterum’s application. While the panel of external experts was not asked to vote on any specific matter, Iterum found the discussion to be encouraging for oral sulopenem’s regulatory prospects. The experts, said CEO Corey Fishman, “acknowledged oral sulopenem as an important treatment option for certain patients with uUTI and agree that the appropriate use of oral sulopenem by treating physicians is critical to limiting antimicrobial resistance.” The FDA had previously rejected oral sulopenem in uUTI, noting in July 2021 that Iterum needed to provide additional clinical data to support an approval. After Previous Rejection, Lexicon’s Insulin Adjunct to Face Adcomm To close out the month, the FDA will convene its Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) On October 31 to discuss Lexicon Pharmaceuticals’ Zynquista (sotagliflozin), which the biotech is proposing as an adjunctive therapy to insulin to control blood glucose levels in patients with type 1 diabetes and chronic kidney disease (CKD). Zynquista’s active ingredient sotagliflozin works by inhibiting the SGLT2 and SGLT1 proteins, which are involved in the absorption of glucose in the kidneys and gastrointestinal tract, respectively. Lexicon first sought type 1 diabetes approval for sotagliflozin in 2018, backing its application with data from the inTandem clinical program, which includes three Phase III trials with around 3,000 patients enrolled. In January 2019, however, the EMDAC was split regarding sotagliflozin’s approvability, with half of the panelists voting against it, citing the risk of diabetic ketoacidosis and other safety issues. Months later, in March 2019, the FDA rebuffed Lexicon’s regulatory bid . Lexicon appealed the FDA’s verdict, though this has since stalled. The biotech refiled its NDA in June 2024, with CEO Lonnel Coats at the time reiterating that the company is “confident in the benefit/risk pro sotagliflozon” for type 1 diabetes and CKD.

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。 在即将到来的10月，将有4款重磅药物有望获得批准，其中包括：Zealand公司胰高血糖素类似物Dasiglucagon、BMS重磅PD-1抑制剂O药新辅助疗法、Camurus公司罕见病疗法Oclaiz以及Iterum Therapeutics公司在研口服碳青霉烯类抗感染药物： Zealand：Dasiglucagon PDUFA日期：2024年10月8日 Dasiglucagon是Zealand公司开发的一款胰高血糖素类似物，它具有独特的稳定性，可以在水溶液的状态下稳定存在。2021年，Dasiglucagon以商品名Zegalogue在美国上市，用于治疗6岁及以上糖尿病成人和儿童的严重低血糖，这是该药物获批的首个适应症，Zegalogue是第一个也是唯一一个用于治疗6岁及以上儿童和成人糖尿病患者严重低血糖的胰高血糖素类似物。Zealand公司同时开发了名为HypoPal的自动注射器，它可以由糖尿病患者自己操作，快速治疗严重低血糖。 两项三期试验（NCT04172441；NCT03777176）和一项正在进行的长期扩展试验（NCT03941236）的数据为该NDA提供了支持。FDA正在对同一NDA进行两部分审查。第1部分涉及Dasiglucagon用于预防和治疗出生7天及以上的先天性高胰岛素血症（CHI）儿童患者的低血糖症，用药时间最长为3周，预计将于10月8日做出决定。第2部分涉及该药物3周以上的使用，为支持第2部分的审查，美国FDA要求对现有的连续血糖监测 (CGM) 数据集进行额外分析，这些数据集被列为第3阶段计划的次要结果指标。提交NDA第2部分的时间将推迟到2024年下半年。 BMS：Opdivo PDUFA日期：2024年10月8日 FDA正在审查BMS重磅PD-1抑制剂Opdivo（nivolumab）与化疗联用作为新辅助疗法用于IIA至IIIB期可切除非小细胞肺癌（NSCLC）患者围手术期治疗的sBLA，PDUFA日期定为2024年10月8日。 该申请得到了一项III期随机、双盲、安慰剂对照、多中心研究CheckMate-77T（NCT04025879）研究数据的支持。 该研究在461名IIA至IIIB期可切除NSCLC患者中评估了新辅助nivolumab联合化疗，序贯手术和nivolumab辅助治疗，对比新辅助化疗联合安慰剂，序贯手术和安慰剂辅助治疗的疗效与安全性。该研究的主要终点是无事件生存期（EFS）。次要终点包括病理完全缓解（pCR）、主要病理缓解（MPR）、总生存期（OS）和安全性。 中位随访25.4个月，NIVO组和化疗组的18个月EFS率为70.2% vs 50.0%（HR=0.58，P<0.001），NIVO组可降低42%的疾病进展或复发、取消手术或死亡风险。研究者评估的EFS观察到相似的获益（HR=0.56）。亚组分析结果中，PD-L1高表达患者有更高的EFS获益。NIVO组和对照组pCR率分别为25.3% vs 4.7%（HR，6.64；95% CI，3.40-12.97）；MPR率分别为35.4% vs. 12.1%（HR，4.01；95% CI，2.48-6.49）。 Camurus：Oclaiz (CAM2029) PDUFA日期：2024年10月21日 2024年3月5日，Camurus公司宣布美国FDA已经受理了该公司用于治疗肢端肥大症患者的Oclaiz（CAM2029）的新药申请（NDA），PDUFA日期为2024年10月21日。CAM2029是一种新型的奥曲肽皮下注射剂，设计方便，每月一次自行给药，提高了奥曲肽的血浆暴露，并能有效控制疾病。 该NDA得到了7项临床研究数据的支持，其中包括两项3期研究（ACROINNOVA 1 [NCT04076462]和ACROINNOVA 2[ NCT04125836]）。 ACROINNOVA 1是一项为期24周的随机、双盲、安慰剂对照研究，共纳入了72名接受标准疗法稳定治疗的肢端肥大症成年患者。研究结果显示，72.2%接受Oclaiz治疗的患者有生化反应，而接受安慰剂治疗的患者只有37.5%（主要终点为第22周和第24周平均胰岛素样生长因子[IGF-1]≤正常值上限[ULN]；P=0.0018）。 ACROINNOVA 2研究对Oclaiz的长期安全性进行了评估，该研究纳入了135名成年肢端肥大症患者。在这项为期52周的研究中，Oclaiz 的安全性与第一代体生长抑素受体配体一致。此外，在整个研究人群中还观察到生化应答率（IGF-1≤1xULN）显著增加。   Iterum：sulopenem etzadroxil/probenecid   PDUFA日期：2024年10月25日 2024年5月31日，Iterum Therapeutics宣布美国FDA已确认收到重新提交的sulopenem etzadroxil/probenecid（舒洛培南口服制剂）新药申请（NDA），用于治疗成年女性无并发症尿路感染（uUTI），PDUFA日期定为2024年10月25日。 sulopenem etzadroxil是一种在研的口服碳青霉烯类抗感染药，已与probenecid合制成双层片剂。重新提交的文件包括REASSURE[NCT05584657]（Sulopenem用于耐药肠杆菌科的uUTI的重新评估），SURE (Sulopenem用于耐药肠杆菌科)1,SURE 2和SURE 3的3期临床试验的数据，其中口服Sulopenem耐受性良好，未发现安全性问题。 REASSURE试验比较了口服Sulopenem和口服Augmentin®对患有尿路感染的成年女性的疗效。结果表明，口服Sulopenem在主要疗效终点（即对 Augmentin®易感致病菌患者的临床和微生物反应）上不劣于Augmentin®（61.7% vs 55%），总体成功率的差异表明口服Sulopenem在统计学上显著优于Augmentin®。 SURE 1 临床试验对患有 uUTI 的成年女性进行了口服Sulopenem和口服环丙沙星的比较，结果表明，对于喹诺酮类非敏感病原体患者，在治愈测试访视中的临床和微生物学反应的主要疗效终点方面，口服Sulopenem比广泛使用的对照药环丙沙星具有统计学优势。 参考资料：各公司官网 -END- 2025CMC-CHINA药博会 • 展位火热预定中！