Thiotepa

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, announced today that the U.S. Food and Drug Administration has granted approval for 100 mg/10mL multi-dose vial of TEPYLUTE, a ready-to-dilute formulation of thiotepa to treat breast and ovarian cancer, that eliminates the need for reconstitution and may reduce preparation time and errors offering more scheduling flexibility for their patients. Shorla Oncology Announces FDA Approval of TEPYLUTE® 100mg, First and Only Ready-to-Dilute Multi-Dose Vial of Thiotepa to Treat Breast and Ovarian Cancer and Commercial Launch of TEPYLUTE 15mg and 100mg Vials in the U.S. “We are pleased to offer another viable treatment option for patients with breast and ovarian cancer,” said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology. “Once opened, our 100mg vial of TEPYLUTE is stable for 14 days when properly stored, giving providers the flexibility they need when preparing and administering this very important treatment. TEPYLUTE is a ready to dilute formulation of a well-established, standard of care oncology drug thiotepa that has been manufactured as freeze-dried powder since the 1950s. “This is a huge win for providers because TEPYLUTE avoids the need for complicated and time-consuming reconstitution,” said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology. We are excited to bring TEPYLUTE to the US Market. It provides consistent dosing accuracy and allows for “just in time” preparation, which benefits everyone, especially patients.” said Rayna Herman, Chief Commercial Officer, Shorla Oncology. The American Cancer Society estimates that more than 300,000 women will be diagnosed with breast cancer in the U.S in 2025.2 About 20,890 women will be diagnosed with ovarian cancer in the U.S. in 2025.3 About Shorla Oncology Shorla Oncology is a privately- held, U.S. and Ireland- based commercial stage specialty pharmaceutical company established by Sharon Cunningham and Orlaith Ryan. The company has an advanced pipeline of innovative oncology drugs for orphan and pediatric cancers. Shorla is focused on indications where existing treatments are limited, in shortage or the drug applications are inadequate for the target population. The company’s growing portfolio brings accessible, affordable and life-saving treatments to patients, delivering a major contribution to patient care. Shorla currently markets three products, Nelarabine for the treatment of T-cell leukemia, JYLAMVO™ for the treatment of acute lymphoblastic leukemia and other indications and IMKELDI for the treatment of Chronic Myeloid Leukemia, Gastrointestinal Stromal Tumors (GISTs) and other indications. For further information, please visit www.shorlaoncology.com. TEPYLUTE® (thiotepa) Injection for Intravenous Use INDICATION TEPYLUTE is an alkylating drug indicated for the treatment of adenocarcinoma of the breast or ovary. IMPORTANT SAFETY INFORMATION WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY • TEPYLUTE may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. • TEPYLUTE should be considered potentially carcinogenic in humans. CONTRAINDICATIONS TEPYLUTE is contraindicated in patients with severe hypersensitivity to thiotepa and in concomitant use with live or attenuated vaccines. WARNINGS AND PRECAUTIONS Myelosuppression : For patients receiving TEPYLUTE for treatment of adenocarcinoma of the breast or adenocarcinoma of the ovary, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with TEPYLUTE may be increased. Perform periodic complete blood counts during the course of treatment with TEPYLUTE. Provide supportive care for infections, bleeding, and symptomatic anemia. Inform patients of the possibility of developing low blood cell counts and the need for hematopoietic progenitor cell infusion. Instruct patients to immediately report to their healthcare provider if bleeding or fever occurs. Hypersensitivity: Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of thiotepa. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with TEPYLUTE, initiate appropriate therapy, and monitor until signs and symptoms resolve. Counsel patients on the signs and symptoms of hypersensitivity and to seek immediate emergency assistance if they develop any of these signs and symptoms. Cutaneous Toxicity: TEPYLUTE and/or its active metabolites may be excreted in part via skin in patients receiving high-dose therapy. Treatment with TEPYLUTE may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of TEPYLUTE. Change the occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of TEPYLUTE. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to TEPYLUTE may occur. Wash the skin thoroughly with soap and water in case the TEPYLUTE solution contacts the skin. Flush mucous membranes in case of TEPYLUTE contact with mucous membranes. Concomitant Use of Live and Attenuated Vaccines: Do not administer live or attenuated viral or bacterial vaccines to a patient treated with TEPYLUTE until the immunosuppressive effects have resolved. Hepatic Veno-Occlusive Disease: Monitor by physical examination, serum transaminases, and bilirubin, and provide supportive care to patients who develop hepatic veno-occlusive disease. Central Nervous System Toxicity: Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior, and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. Do not exceed the recommended dose of TEPYLUTE. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of TEPYLUTE and provide supportive care. Carcinogenicity: Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals. Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of secondary malignancy with the use of TEPYLUTE. Inform patients that TEPYLUTE can increase the risk of secondary malignancy. Polyethylene glycol (PEG) 400 toxicity : TEPYLUTE contains a high concentration of PEG 400. Based on findings in animals, administration of high amounts of PEG 400 may cause damage to the kidneys and liver at dosages higher than recommended. When prescribing TEPYLUTE, take into consideration the PEG 400 load from concomitant medications. Embryo-Fetal Toxicity: Based on the mechanism of action and findings in animals, TEPYLUTE can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of TEPYLUTE in pregnant women. Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥1 mg/kg (3.2 mg/m 2 ), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m 2 ), based on body-surface area. Thiotepa given by the IP route was teratogenic in rats at doses ≥3 mg/kg (21 mg/m 2 ), approximately equal to the maximum recommended human therapeutic dose, based on body-surface area. Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2 ), approximately two times the maximum recommended human therapeutic dose based on body-surface area. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use highly effective contraception during TEPYLUTE treatment and for 6 months after therapy/the last dose. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise males with female partners of reproductive potential to use effective contraception during TEPYLUTE treatment and for 1 year after therapy/the last dose. ADVERSE REACTIONS The most common adverse reactions (incidence greater than 10%) are neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase (AST), elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria, and rash. The clinically significant adverse reactions include myelosuppression, infection, hypersensitivity, cutaneous toxicity, hepatic veno-occlusive disease, central nervous system toxicity, and carcinogenicity. DRUG INTERACTIONS Effect of Cytochrome CYP3A Inhibitors and Inducers: In vitro studies suggest that thiotepa is metabolized by CYP3A4 and CYP2B6 to its active metabolite triethylene phosphoramide (TEPA). Avoid coadministration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with thiotepa due to the potential effects on efficacy and toxicity. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 modulators cannot be avoided, closely monitor for adverse drug reactions. Effect of TEPYLUTE on Cytochrome CYP2B6 Substrates: In vitro studies suggest that thiotepa inhibits CYP2B6. Thiotepa may increase the exposure of drugs that are substrates of CYP2B6 in patients; however, the clinical relevance of this in vitro interaction is unknown. The administration of thiotepa with cyclophosphamide in patients reduces the conversion of cyclophosphamide to the active metabolite, 4‑hydroxycyclophosphamide; the effect appears sequence-dependent with a greater reduction in the conversion to 4-hydroxycyclophosphamide when thiotepa is administered 1.5 hours before the intravenous administration of cyclophosphamide compared to administration of thiotepa after intravenous cyclophosphamide. The reduction in 4-hydroxycyclophosphamide levels may potentially reduce the efficacy of cyclophosphamide treatment. USE IN SPECIFIC POPULATIONS Pregnancy: TEPYLUTE can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action. Limited available data on thiotepa use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of thiotepa to pregnant mice and rats during organogenesis produced teratogenic effects (neural tube defects and malformations of the skeletal system of the fetus) at doses approximately 0.125 and 1 times, respectively, the maximum recommended human daily dose on a mg/m2 basis. Thiotepa was lethal to rabbit fetuses at approximately 2 times the maximum recommended human therapeutic dose based on body-surface area. Consider the benefits and risks of TEPYLUTE for the mother and possible risks to the fetus when prescribing TEPYLUTE to a pregnant woman. Lactation: There is no information regarding the presence of thiotepa in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including the potential for tumorigenicity shown for thiotepa in animal studies, advise patients not to breastfeed during TEPYLUTE treatment and for 1 week after therapy/the last dose. Females and Males of Reproductive Potential: TEPYLUTE can cause fetal harm when administered to a pregnant woman. Pregnancy Testing - Verify the pregnancy status of females of reproductive potential before initiating TEPYLUTE therapy. Contraception for Females - Advise females of reproductive potential to avoid pregnancy during TEPYLUTE treatment and for 6 months after therapy/the last dose. Advise females to immediately report pregnancy. Contraception for Males - TEPYLUTE may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during TEPYLUTE treatment and for 1 year after therapy/the last dose. Infertility - Based on nonclinical findings, male and female fertility may be compromised by treatment with TEPYLUTE. Advise patients that TEPYLUTE can produce infertility. Inform male patients about the possibility of sperm conservation before the start of therapy. Pediatric Use: Safety and effectiveness of TEPYLUTE in neonates have not been established. Safety and effectiveness of TEPYLUTE for the treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary in pediatric patients have not been established. Geriatric Use: Clinical studies of thiotepa for treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary did not include sufficient numbers of subjects aged 65 years and over to determine whether elderly subjects respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Renal Impairment: In patients with moderate (creatinine clearance [CLcr] of 30 mL/min to 59 mL/min) renal impairment, decreased renal excretion may result in increased plasma levels of thiotepa and TEPA. This may result in increased toxicity. Monitor patients with moderate to severe (CLcr <30 mL/min) renal impairment for signs and symptoms of toxicity following treatment with TEPYLUTE for an extended period of time. Hepatic Impairment: Thiotepa is extensively metabolized in the liver. Patients with moderate (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal and any AST) hepatic impairment may have increased plasma levels of thiotepa. This may result in toxicity. Monitor patients with moderate to severe (bilirubin levels greater than 3 times the upper limit of normal and any AST) hepatic impairment for signs and symptoms of toxicity following treatment with TEPYLUTE for an extended period of time. To report suspected adverse reactions, contact Shorla Oncology at 1-844-668-3940 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Print: Please see the accompanying full Prescribing Information, including Boxed Warning. For Digital: Please click here for full Prescribing Information, including Boxed Warning. All trademarks are the property of Shorla Oncology. ©SHORLA ONCOLOGY® 2025. PRO-TEP-1377-v1 04/2025

编者按：本文来自米内网，作者苍穹；赛柏蓝授权转载，编辑凯西日前，国家医保局发文明确2025国谈时间或将前移，85款儿科药有望冲刺新国谈，独家品种（含剂型独家，下同）为主力军。01超330个儿科药来势汹汹石四药、健民......大展拳脚近年来我国儿科药市场销售额均保持良好的增长态势，除2020年受疫情影响首次出现下滑，其余年份销售额增速均在6%以上，市场潜力十足。其中在中国三大终端六大市场，儿科中成药2023年销售规模突破180亿元，2024上半年收获超95亿元，预计全年销售额将再创新高。近年来中国三大终端六大市场儿科中成药销售趋势（单位：万元）伴随临床用药需求的激增，近年来儿科药申报量、获批量均呈现明显上升趋势。2020-2024年在中国获批上市的儿科药数量分别为26个、47个、66个、92个和106个，五年间合计获批新品数超过330个，进一步缓解儿童用药适宜剂型少、规格少等问题。据不完全统计，2023-2024年获批的儿科药中，约有55个品种为首次获批上市，其中口服溶液剂占比接近四成，满足儿科用药便利性的需求；治疗大类上以神经系统药物、抗肿瘤和免疫调节剂为主，分别占13个和10个席位，消化系统及代谢药（9个）、血液和造血系统药物（5个）、全身用抗感染药物（5个）则位居其后。具体产品方面，恒瑞医药的注射用塞替派可用于重型β-地中海贫血儿童（＜18周岁）异基因造血干细胞移植（allo-HSCT）前预处理，是国内首个获批移植预处理相关适应症的塞替派产品。据此前恒瑞公告，该产品已先后于2018年和2022年在美国、欧洲获批上市。它的到来无疑为移植治愈儿童重型β-地贫带来了新希望。小儿豉翘清热糖浆为济川药业的独家儿科感冒中成药，是在小儿豉翘清热颗粒基础上改良所得。小儿豉翘清热颗粒近年来在中国三大终端六大市场销售额保持快速增长，2023年拿下超27亿元的佳绩。小儿紫贝宣肺糖浆为健民药业的独家儿科止咳祛痰中成药，其组方源于国家级名老中医经验方，具有良好的临床应用基础，在治疗小儿急性支气管炎风热犯肺证咳嗽方面疗效显著，且安全性好。近年来中国三大终端六大市场小儿豉翘清热颗粒销售趋势（单位：万元）从审评审批路径上看，共有46个药品（不含预防用生物制品，下同）通过优先审评审批程序得以加快上市，其中独家品种有33个，占比超过七成，包括兴齐眼药的延缓儿童近视进展用药硫酸阿托品滴眼液、石家庄四药的罕见病Dravet综合征治疗药司替戊醇干混悬剂、亿帆医药用于先天性高胰岛素性低血糖血症的二氮嗪口服混悬液、恒瑞医药的广谱抗肿瘤药环磷酰胺胶囊、以及辉瑞用于治疗青少年特应性皮炎的阿布昔替尼片等。2023-2024年通过优先审评审批获批上市的儿科药注：带*为独家品种0285款儿科药剑指新国谈独家品种成“爆款”为了让更多患儿用上“质优价廉”的儿科药，推进其加快准入医保成为国家的重要任务之一。比如：2019-2024版医保目录调整方案中均明确指出，重点调整及优先纳入儿科药，其中2021版医保目录经谈判准入的34个独家儿科药平均降价55.6%；2024版医保目录也纳入了多款儿科药，不乏济川药业的小儿豉翘清热糖浆和盐酸非索非那定干混悬剂、健民药业的小儿紫贝宣肺糖浆、石四药的司替戊醇干混悬剂、诺华的盐酸伊普可泮胶囊等独家品种。据今年1月国家医保局召开的新闻发布会透露：2025国谈或在4月启动申报，争取9月结束医保谈判、发布新版医保目录；新药申报时间为2025年4月1日-2025年5月底。据不完全统计，目前至少有85款儿科药有望参与今年新国谈，其中独家品种“霸屏”，有57个产品在列；从剂型上看，溶液剂和注射剂为主力军，合计占比超60%；按治疗大类统计，神经系统药物、消化系统及代谢药在数量上领跑，分别占17个和16个席位。有望参与2025国谈的儿科药注：带*为独家品种健民药业的小儿牛黄退热贴膏是近日获批上市的中药1.1类新药，具有退热解表、清热解毒的功效，用于小儿急性上呼吸道感染风热证所致的发热（38.5℃及以下）。该新药的上市为急性上呼吸道感染风热证所致的1至5岁发热儿童患者提供了新的治疗选择。青峰医药的口服溶液用盐酸万古霉素是一种糖肽类抗生素，用于革兰氏阳性菌所致的严重感染，如心内膜炎、骨髓炎、败血症或软组织感染等。凭借独特药理特性和给药优势，该产品为肠道耐药菌感染患者，尤其是儿童患者，提供了更高效、安全的治疗方案。2023年中国三大终端六大市场万古霉素销售规模接近24亿元，同比增长6.14%。氯法拉滨注射液和二氮嗪口服混悬液均为亿帆医药近年获批上市的新品，其中前者用于治疗儿童难治性/复发性急性淋巴细胞白血病，后者可用于先天性高胰岛素性低血糖血症（CHI）。据悉，上述两款儿科药均已出现在2024国谈初审药品名单，今年能否一鼓作气共同挺进2025版医保目录，我们拭目以待。五月将至，新一轮国谈虽“迟迟未有动静”，但启动时间前移似乎是大势所趋。届时，2025版医保目录将有哪些新亮点？又有哪些品种能成功入选？来源：米内网数据库、国家医保局官网等；数据统计截至4月22日，如有疏漏，欢迎指正。END内容沟通：郑瑶（13810174402）