STOCKHOLM, Dec. 20, 2023 /PRNewswire/ -- Calliditas Therapeutics AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ('Calliditas'), today announced that the U.S. Food and Drug Administration (FDA) has approved TARPEYO (budesonide) delayed release capsules to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression.

斯德哥尔摩，2023年12月20日/PRNewswire/--Calliditas Therapeutics AB（纳斯达克：CALT）（纳斯达克-斯德哥尔摩：CALTX）（“Calliditas”）今天宣布，美国食品和药物管理局（FDA）已批准TARPEYO（布地奈德）缓释胶囊，以减少患有疾病进展风险的原发性免疫球蛋白A肾病（IgAN）的成年人的肾功能丧失。

TARPEYO was first approved in December 2021 under accelerated approval, based on the surrogate marker of proteinuria. Marking a significant milestone, TARPEYO is now the first fully FDA-approved treatment for IgAN based on a measure of kidney function..

基于蛋白尿的替代标志物，TARPEYO于2021年12月首次获得加速批准。标志着一个重要的里程碑，TARPEYO现在是FDA批准的第一种基于肾功能测量的IgAN治疗方法。。

TARPEYO (investigational name NEFECON) is the only FDA-approved treatment for IgAN to significantly reduce the loss of kidney function.

TARPEYO（研究名称NEFECON）是FDA批准的唯一可显着减少肾功能丧失的IgAN治疗方法。

TARPEYO is now approved with a confirmed and statistically significant benefit over placebo (p<0.0001) in estimated glomerular filtration rate (eGFR) over the two-year period that consisted of 9 months of treatment with TARPEYO plus optimized renin-angiotensin system inhibitor (RASi) or placebo and optimized RASi and 15 months of follow-up off study drug..

TARPEYO现在被批准在两年的估计肾小球滤过率（eGFR）方面优于安慰剂（p<0.0001），两年期间包括用TARPEYO加优化的肾素-血管紧张素系统抑制剂（RASi）或安慰剂和优化的RASi治疗9个月，以及15个月的随访研究药物。。

At 2 years, there was a 6.11 mL/min/1.73 m2 decline in eGFR in the TARPEYO group compared with a 12.0 mL/min/1.73 m2 decline in the placebo group (p<0.0001), representing 50% less deterioration of kidney function in TARPEYO-treated patients compared to placebo-treated patients over the 2-year period..

在2年时，TARPEYO组的eGFR下降了6.11 mL/min/1.73 m2，而安慰剂组的eGFR下降了12.0 mL/min/1.73 m2（p<。。

TARPEYO is a B-cell immunomodulator designed to target a source of the disease and reduce the production of pathogenic galactose-deficient IgA1 antibodies, which cause IgAN.1-3

TARPEYO是一种B细胞免疫调节剂，旨在靶向疾病来源并减少引起IgAN.1-3的致病性半乳糖缺陷型IgA1抗体的产生

Significant proteinuria reduction achieved with TARPEYO plus RASi at 9 months was durable and maintained throughout the 15-month off-drug period.

TARPEYO加RASi在9个月时实现的显着蛋白尿减少是持久的，并且在整个15个月的停药期间保持不变。

The FDA approval is for adults with primary IgAN who are at risk of disease progression, irrespective of proteinuria levels.

FDA批准用于患有原发性IgAN的成年人，无论蛋白尿水平如何，他们都有疾病进展的风险。

'The evidence of sustained reductions in proteinuria and a clinically significant reduction in the loss of eGFR, which can help slow the progression towards dialysis or transplant care, highlights the potential of TARPEYO as a disease-modifying agent in IgAN,' said Richard Lafayette, MD, FACP, Stanford Healthcare.

斯坦福大学医疗保健中心FACP医学博士理查德·拉斐特（Richard Lafayette）说：“有证据表明，蛋白尿持续减少，eGFR损失在临床上显着减少，这有助于减缓透析或移植护理的进展，突显了TARPEYO作为IgAN疾病缓解剂的潜力。”。

'TARPEYO provides physicians and patients an effective treatment option to help improve disease outcomes.'.

“TARPEYO为医生和患者提供了一种有效的治疗选择，以帮助改善疾病的预后。”。

The approval is based on data from the Company's Phase 3 NefIgArd clinical trial, a randomized, double-blind, multicenter, study that assessed the efficacy and safety of TARPEYO dosed at 16 mg once daily versus placebo on a background of optimized RASi therapy in adult patients with primary IgAN.

该批准是基于该公司的3期NefIgArd临床试验的数据，该试验是一项随机，双盲，多中心的研究，评估了在成人原发性IgAN患者中优化RASi治疗的背景下，每天一次服用16 mg TARPEYO与安慰剂的疗效和安全性。

'We are thrilled that adult IgAN patients at risk for progression in the United States can now have access to this pioneering treatment option that could help preserve their kidney function and, hence, impact the progression of their disease,' said Renee Aguiar-Lucander, CEO of Calliditas. 'This medicine was specifically developed to target an underlying cause of IgAN, and I would like to express my gratitude to the Calliditas team, study investigators, and most importantly, the patients and caregivers who made this significant milestone possible.

Calliditas首席执行官蕾妮·阿吉亚·卢坎德（Renee Aguiar Lucander）说：“我们很高兴美国有进展风险的成年IgAN患者现在可以获得这种开创性的治疗选择，这可能有助于保护他们的肾功能，从而影响他们疾病的进展。”这种药物是专门针对IgAN的根本原因而开发的，我要感谢Calliditas团队，研究调查人员，最重要的是，使这一重要里程碑成为可能的患者和护理人员。

I am incredibly proud of the team's unwavering commitment to the goal of preventing end-stage renal disease in patients with this challenging rare disease.'.

我为团队坚定不移地致力于预防这种具有挑战性的罕见疾病患者的终末期肾病的目标而感到无比骄傲。”。

TARPEYO was generally well-tolerated in the Phase 3 NefIgArd clinical trial. The most common adverse reactions (≥5%) in this study were peripheral edema, hypertension, muscle spasms, acne, headache, URT infection, face edema, weight increased, dyspepsia, dermatitis, arthralgia, and white blood cell count increased.

在3期NefIgArd临床试验中，TARPEYO通常耐受性良好。本研究中最常见的不良反应（≥5%）是外周水肿，高血压，肌肉痉挛，痤疮，头痛，URT感染，面部水肿，体重增加，消化不良，皮炎，关节痛和白细胞计数增加。

Please see Important Safety Information below..

请参阅下面的重要安全信息。。

'This first-ever IgAN treatment to get a full approval based on kidney function represents a beacon of hope for the entire IgA nephropathy community and signifies a critical step forward in the battle against IgAN,' said Bonnie Schneider, director and cofounder of the IgAN Foundation. 'The foundation is elated and personally this is so rewarding and validating after a near 20-year journey since founding this volunteer-run organization to raise awareness and promote research for IgAN.'.

IgAN基金会董事兼联合创始人邦妮·施奈德（BonnieSchneider）说：“这是首次基于肾功能获得全面批准的IgAN治疗，代表了整个IgA肾病社区的希望灯塔，标志着对抗IgAN的斗争迈出了关键的一步。”该基金会非常高兴，就个人而言，这是非常有益和有效的，因为自成立这个志愿者组织以来，该组织已经走过了近20年的历程，旨在提高人们对IgAN的认识并促进其研究。”。

TARPEYO is available exclusively through Calliditas specialty pharmacy, Biologics by McKesson. To get started with TARPEYO, prescribers must fill out a TARPEYO Touchpoints® Enrollment Form, which serves as a prescription. This Enrollment Form will connect patients with all the benefits provided by TARPEYO Touchpoints®, including financial aid programs that can eliminate or reduce out-of-pocket costs, assistance from our team of care navigators, pharmacists, and nurse educators; and the convenience of at-home, next-day delivery.

TARPEYO仅可通过McKesson的生物制剂公司Calliditas specialty pharmacy获得。要开始使用TARPEYO，开处方的人必须填写TARPEYO Touchpoints®登记表，该表可作为处方。此登记表将使患者获得TARPEYO Touchpoints®提供的所有好处，包括可以消除或减少自付费用的财务援助计划，以及我们护理导航员，药剂师和护士教育工作者团队的帮助；而且方便在家，第二天送货。

At Calliditas, we believe that the cost of treatment should never be a barrier to care. With TARPEYO Touchpoints®, 97% of patients taking TARPEYO have paid less than $10 per prescription, and 88% have paid nothing at all..

在Calliditas，我们认为治疗费用永远不应该成为护理的障碍。使用TARPEYO Touchpoints®，服用TARPEYO的患者中有97%的患者每张处方的费用不到10美元，而88%的患者根本没有支付任何费用。。

IndicationTARPEYO is indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

适应症Tarpeyo可减少有疾病进展风险的原发性免疫球蛋白A肾病（IgAN）成人的肾功能丧失。

Important Safety InformationContraindications: TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations.

重要安全信息禁忌症：对布地奈德或TARPEYO的任何成分过敏的患者禁用TARPEYO。其他布地奈德制剂也发生了严重的超敏反应，包括过敏反应。

Warnings and PrecautionsHypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended.

警告和预防皮质激素过多和肾上腺轴抑制：当长期使用皮质类固醇时，可能会发生全身效应，如皮质激素过多和肾上腺抑制。皮质类固醇可以降低下丘脑-垂体-肾上腺（HPA）轴对压力的反应。在患者接受手术或其他压力情况下，建议补充全身皮质类固醇。

When discontinuing therapy or switching between corticosteroids, monitor for signs of adrenal axis suppression..

停止治疗或更换皮质类固醇时，监测肾上腺轴抑制的迹象。。

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C).

由于口服布地奈德的全身暴露增加，中度至重度肝功能损害（分别为Child-Pugh B级和C级）的患者可能会增加皮质醇增多症和肾上腺轴抑制的风险。避免用于严重肝损伤患者（Child-Pugh C级）。

Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B)..

监测中度肝功能损害（Child-Pugh B级）患者皮质醇增多的体征和/或症状。。

Risks of immunosuppression: Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids.

免疫抑制的风险：服用抑制免疫系统药物的患者比健康人更容易感染。例如，水痘和麻疹在易感患者或服用免疫抑制剂量皮质类固醇的患者中可能会有更严重甚至致命的病程。

Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections, or ocular herpes simplex. Avoid exposure to active, easily-transmitted infections (e.g., chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines..

避免对活动性或静止性结核感染患者进行皮质类固醇治疗；未经治疗的真菌，细菌，全身病毒或寄生虫感染或眼部单纯疱疹。避免接触活动性、易传播的感染（如水痘、麻疹）。皮质类固醇治疗可能会降低对某些疫苗的免疫反应。。

Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where corticosteroids may have unwanted effects..

其他皮质类固醇作用：TARPEYO是一种全身可用的皮质类固醇，预计会引起相关的不良反应。监测患有高血压，糖尿病前期，糖尿病，骨质疏松症，消化性溃疡，青光眼或白内障，或有糖尿病或青光眼家族史，或皮质类固醇可能产生不良影响的任何其他疾病的患者。。

Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO treated patients, and ≥2% higher than placebo) were peripheral edema (17%), hypertension (12%), muscle spasms (12%), acne (11%), headache (10%), upper respiratory tract infection (8%), face edema (8%), weight increased (7%), dyspepsia (7%), dermatitis (6%), arthralgia (6%), and white blood cell count increased (6%)..

不良反应：在临床研究中，TARPEYO最常见的不良反应（发生率≥5%，比安慰剂高≥2%）是外周水肿（17%），高血压（12%），肌肉痉挛（12%），痤疮（11%），头痛（10%），上呼吸道感染（8%），面部水肿（8%），体重增加（7%），消化不良（7%），皮炎（6%），关节痛（6%），白细胞计数增加（6%）。。

Drug interactions: Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide..

药物相互作用：布地奈德是CYP3A4的底物。避免使用强效CYP3A4抑制剂，如酮康唑、伊曲康唑、利托那韦、茚地那韦、沙奎那韦、红霉素和环孢素。避免摄入含TARPEYO的葡萄柚汁。摄入抑制CYP3A4活性的葡萄柚汁可以增加布地奈德的全身暴露。。

Use in specific populationsPregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN.

在特定人群中使用妊娠：已发表的病例系列，流行病学研究以及孕妇口服布地奈德的评论的现有数据尚未确定与药物相关的重大出生缺陷，流产或其他不良孕产妇或胎儿结局的风险。与IgAN相关的母亲和胎儿存在风险。

Infants exposed to in-utero corticosteroids, including budesonide, are at risk for hypoadrenalism..

暴露于子宫内皮质类固醇（包括布地奈德）的婴儿有肾上腺功能减退的风险。。

Please see Full Prescribing Information.

请参阅完整的处方信息。

About TARPEYOTARPEYO is an oral 4mg delayed release formulation of budesonide, designed to remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer's patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy.

关于TARPEYOTARPEYO是一种口服4mg布地奈德缓释制剂，旨在保持完整直至到达回肠。每个胶囊含有布地奈德包被的珠子，其靶向回肠中存在的粘膜B细胞，包括派伊尔斑，其负责产生导致IgA肾病的半乳糖缺陷型IgA1抗体（Gd-Ag1）。

1-3.

1-3.

About the NeflgArd StudyNefIgArd was a global, Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of TARPEYO 16 mg once daily vs placebo in adult patients with primary IgAN (N=364) as an addition to optimized RASi therapy. Patients were randomized 1:1 to receive 16 mg/day oral capsules of TARPEYO or matching placebo for 9 months, followed by a 15-month observational follow-up period without the study drug..

关于NeflgArd研究Nefigard是一项全球性的3期随机双盲安慰剂对照多中心研究，旨在评估TARPEYO 16 mg每日一次与安慰剂治疗成人原发性IgAN患者（N=364）的疗效和安全性，作为优化RASi治疗的补充。患者以1:1的比例随机接受16毫克/天的TARPEYO口服胶囊或匹配的安慰剂治疗9个月，然后进行15个月的观察随访，无需研究药物。。

The primary efficacy endpoint was time-weighted average of eGFR over 2 years. The time-weighted average of eGFR over 2 years showed a statistically significant treatment benefit with TARPEYO versus placebo (difference 5•05 mL/min per 1•73 m² [95% CI 3•24 to 7•38], p<0•0001).

主要疗效终点是2年内eGFR的时间加权平均值。2年内eGFR的时间加权平均值显示，TARPEYO与安慰剂相比具有统计学意义的治疗益处（每1.73平方米差异5.05毫升/分钟[95%可信区间3.24至7.38]，p<0.0001）。

The favorable effect of TARPEYO on eGFR was seen by Month 3 (the earliest assessment) and did not appear to increase in magnitude over two years.  At the end of Year 2, there was a 5.9 mL/min/1.73 m2 difference in the mean change from baseline in eGFR between TARPEYO and placebo (95% CI: 3.3 to 8.5 mL/min/1.73 m2; p<0.0001).

TARPEYO对eGFR的有利影响在第3个月（最早的评估）就已经出现，并且在两年内似乎没有增加。在第2年末，TARPEYO和安慰剂组eGFR的平均变化与基线相比有5.9 mL/min/1.73 m2的差异（95%CI:3.3至8.5 mL/min/1.73 m2；p＜0.0001）。

The effect on kidney function seen during the 9-month treatment period persisted following completion of treatment through the end of the study but the overall effect on the long-term rate of decline has not been established..

9个月治疗期间对肾功能的影响在治疗结束后一直持续到研究结束，但对长期下降率的总体影响尚未确定。。

The most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO treated patients and ≥2% higher than placebo) were peripheral edema (17%), hypertension (12%), muscle spasms (12%), acne (11%), headache (10%), upper respiratory tract infection (8%), face edema (8%), weight increase (7%), dyspepsia (7%), dermatitis (6%), arthralgia (6%), and white blood cell count increase (6%)..

TARPEYO最常见的不良反应是外周水肿（17%），高血压（12%），肌肉痉挛（12%），痤疮（11%），头痛（10%），上呼吸道感染（8%），面部水肿（8%），体重增加（7%），消化不良（7%），皮炎（6%），关节痛（6%）和白细胞计数增加（6%）。。

About Primary Immunoglobulin A NephropathyPrimary immunoglobulin A nephropathy (IgAN or Berger's Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 is recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney.2,4 This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end- stage renal disease.

关于原发性免疫球蛋白A肾病原发性免疫球蛋白A肾病（IgAN或伯格氏病）是一种罕见的，进行性的慢性自身免疫性疾病，会攻击肾脏，并在半乳糖缺乏的IgA1被自身抗体识别时发生，产生IgA1免疫复合物，沉积在肾脏的肾小球系膜中。2,4肾脏中的这种沉积可导致进行性肾损伤，并可能导致终末期肾病的临床过程。

IgAN most often develops between the late teens and late 30s.2,5.

IgAN最常在十几岁到三十岁之间发展。2,5。

CONTACT:For further information, please contact:Åsa Hillsten, Head of IR and Sustainability, CalliditasTel.: +46 76 403 35 43, email: [email protected]

联系人：欲了解更多信息，请联系CalliditasTel IR和可持续发展负责人Åsa Hillsten：+46 76 403 35 43，电子邮件：[受电子邮件保护]

The information in the press release is information that Calliditas is obliged to make public pursuant to the EU Market Abuse Regulation. The information was sent for publication, through the agency of the contact person set out above, on December 20, 2023 at 22:15 p.m. CET.

新闻稿中的信息是Calliditas根据欧盟市场滥用法规有义务公开的信息。该信息于2023年12月20日下午22:15通过上述联系人的代理发送发布。

The following files are available for download:

以下文件可供下载：

https://mb.cision.com/Main/16574/3897482/2509311.pdf

https://mb.cision.com/main/16574/3897482/2509311.pdf

CALT_TARPEYO_PDUFA_PR_ENG

CALT_TARPEYO_PDUFA_PR_ENG