Voclosporin

点击“蓝字”关注我们 引言：系统性红斑狼疮肾炎（LN）是系统性红斑狼疮（SLE）最严重的器官受累表现之一，影响约30%~60%的SLE患者。LN不仅会导致快速的肾小球损伤，若不及时治疗，还可能进展为终末期肾病（ESKD）。近年来，随着对LN病理机制的深入研究以及新疗法的不断涌现，其临床管理取得了显著进展。本文将基于最新的研究成果，总结LN管理的十大建议，以期为临床医生提供实用的指导。 一、根据肾脏病理严重程度选择药物并迅速治疗 LN的诊断通常以血尿、蛋白尿或血清肌酐升高为临床表现，而肾活检不仅能确诊LN，还能提供关于病变活动性、慢性化和严重程度的重要信息。国际肾脏病理学会（ISN/RPS）分类中，III型和IV型LN是最严重的活动性LN类型，常伴有肾小球毛细血管和系膜的免疫介导急性损伤，若不及时治疗，可能导致不可逆的肾小管间质损伤。研究表明，延迟诊断与不良肾结局密切相关，肾活检延迟超过6个月的患者，其发生ESKD的风险增加9倍。 在治疗时，应根据肾脏病理的活动性和慢性化程度选择合适的药物和剂量。例如，对于存在广泛新月体的患者，需采取更积极的治疗策略；而对于存在广泛慢性病变（如肾小管萎缩和间质纤维化）的患者，则预示着肾功能预后不佳。此外，还需注意一些未被ISN/RPS分类涵盖的额外病变，如血栓性微血管病（TMA），其与更严重的临床病理特征和不良肾结局相关，治疗时需考虑抗凝和血浆置换。 二、参考既往疾病复发史和治疗反应选择最佳治疗方案 LN的病程和治疗反应因患者而异，患者的年龄、遗传背景、临床表型、疾病持续时间和严重程度等因素均会影响风险评估和药物选择。既往的疾病复发次数和严重程度反映了患者对药物的暴露情况以及后续发生毒性和累积损伤的风险。因此，在选择治疗方案时，需详细记录患者对各种免疫抑制药物的既往反应和耐受性。 此外，SLE是一种易复发的疾病，但不同患者的复发风险差异较大。维持免疫抑制治疗可预防复发，其中吗替麦考酚酯（MPA）优于硫唑嘌呤，并被推荐与抗疟药联合使用。目前的指南建议至少维持免疫抑制治疗3年，但在实践中，许多患者会长期使用低剂量免疫抑制药物。关于维持免疫抑制治疗的最佳持续时间仍存在不确定性，需根据患者的个体差异进行调整。 三、避免过度使用糖皮质激素和其他免疫抑制药物以预防短期和长期毒性 自20世纪60年代以来，大剂量糖皮质激素一直被用于治疗严重的SLE和LN。然而，随着当前联合免疫抑制治疗方案的发展，减少糖皮质激素暴露是可行的，且不影响治疗效果。目前，严重的LN初始治疗通常从每天约500 mg的甲泼尼龙静脉脉冲治疗2-3天开始，随后口服泼尼松并逐渐减量。糖皮质激素的初始剂量和减量方案因医生而异，一般建议初始泼尼松剂量不超过0.8mg/kg。 在维持治疗阶段，建议稳定患者的泼尼松剂量不超过5 mg/天。近期数据显示，将贝利尤单抗（belimumab）添加到标准治疗中可改善治疗反应，降低复发率，并在一些真实世界队列中允许减少糖皮质激素剂量。对于存在持续蛋白尿的患者，尤其是那些伴有膜性病变的患者，添加钙调磷酸酶抑制剂（CNI）可能有益。在糖皮质激素和吗替麦考酚酯的基础上添加伏环孢素可更有效地减少蛋白尿，而他克莫司在治疗膜性LN患者的持续蛋白尿方面也显示出效果。 四、治疗心血管和代谢风险因素以预防不良心血管和代谢结局 心血管风险因素，如高血压、高脂血症和糖尿病，在LN患者中较为常见，且是心血管发病率和死亡率的重要贡献因素。随着时间的推移，这些风险因素的负担会因患者年龄增长、慢性肾病（CKD）进展以及治疗相关不良反应而增加。EULAR对SLE管理的建议指出，传统的动脉粥样硬化风险评估工具（如Framingham风险评分）会低估SLE患者的心血管风险。 因此，应定期监测传统的心血管风险因素以及糖皮质激素和CNI等药物的代谢副作用。对于高血压、高脂血症等患者，首选肾素-血管紧张素系统（RAS）阻滞剂、他汀类等药物治疗。 五、预防因免疫抑制导致的感染并发症 感染是SLE患者的主要死亡原因之一，也是LN患者发病率和死亡率的重要来源。在疾病复发（“诱导”阶段）期间，患者因接受高强度免疫抑制治疗而感染风险最高，但在疾病静止期接受维持免疫抑制治疗的患者也可能发生严重感染。虽然为了快速控制疾病需要给予足够的免疫抑制剂量，但应避免过度免疫抑制，因为随着免疫抑制负担的增加，机会性感染的风险也会增加。肺孢子菌肺炎（PJP）是一种公认的机会性感染，与不良预后相关。当泼尼松暴露量超过20mg/天超过4周，或糖皮质激素与其他免疫抑制药物联合使用时，必须进行PJP预防。 抗感染预防的最佳持续时间尚未明确，应综合考虑免疫抑制治疗的类型、剂量和持续时间，以及宿主风险因素，如年龄和合并症。 六、注意慢性肾脏病（CKD）的严重程度和肾脏储备，因为它们影响患者的风险特征并指导治疗选择 CKD在LN患者中较为常见，因为活动性肾炎的炎症会破坏肾单位并在肾脏中形成瘢痕。由于血清肌酐水平可能在肾功能显著受损时仍处于“正常”范围内，尤其是在身材较小、肌肉量少的亚洲女性患者中，CKD常被低估。据报道，CKD的发生率为10%~50%，但由于许多报告将CKD定义为估算肾小球滤过率（eGFR）小于60ml/min/1.73m2，实际患病率可能被低估。 肾炎复发、治疗不依从、高血压和蛋白尿会促进CKD的进展。此外，患者的肾脏储备对决定维持免疫抑制减量或停药的速度也很重要，因为再次发生肾炎复发会显著加速CKD的进展。还应在CKD患者的治疗中纳入肾脏保护药物，包括RAS阻滞剂，以及可能的钠-葡萄糖共转运蛋白2抑制剂、非甾体类盐皮质激素受体拮抗剂和胰高血糖素样肽-1受体激动剂。 七、以长期和整体视角管理患者，以最小化肾衰竭、早死和其他不良结局的终身风险 SLE主要影响年轻人，约10%~20%的患者在儿童期发病。预防终身肾衰竭和早死的风险，同时保持高生活质量并尽量减少并发症，是最终目标。因此，临床管理决策应纳入这些长期视角，以预防CKD的进展，维持心血管健康，保护生育能力，维持骨骼健康，并尽量减少感染、心血管疾病和恶性肿瘤等风险。 肿瘤是LN患者死亡的重要原因，例如非霍奇金淋巴瘤、肺癌和乳腺癌等。暴露于免疫抑制剂，尤其是细胞毒性药物如环磷酰胺，已被记录为风险因素。 长期骨骼健康是LN患者的一个常见问题，骨质疏松症和骨质减少症较为常见，增加了外周和椎体骨折的风险，这不仅影响生活质量，还增加了发病率和死亡率。值得注意的是，儿童和青少年SLE患者更容易发生骨质疏松症，因为他们通常在达到峰值骨量之前就有较高的糖皮质激素累积暴露。 八、与风湿病学家和其他医疗专业人员联合护理，以解决非肾脏和心理社会问题以及生活质量 LN患者常有各种肾外表现。对于有显著症状负担或严重肾外疾病的患者，应与风湿病学家和其他相关专业人员联合管理，因为治疗较为复杂。另一方面，由风湿病学家管理的LN患者可以从与肾病学家的联合护理中受益，尤其是那些有显著CKD和/或疑似肾炎复发的患者。通过纳入专科护士、临床心理学家、社会工作者或药剂师等其他相关医疗专业人员，可以改善整体护理质量，他们可以帮助加强患者教育并解决任何心理社会障碍。 九、通过建立良好关系确保治疗依从性 在SLE患者中，治疗不依从现象较为普遍，这会导致疾病复发、更高的急性护理利用、住院治疗以及不良的患者结局。治疗不依从的相关因素包括低社会经济地位或健康素养、患者误解以及显著的治疗相关副作用。在管理LN患者的长期过程中，建立良好关系并确保患者对治疗的依从性是一项持续的努力。应在随访中评估依从性，并通过开放和非评判性的讨论解决不依从的原因。测量药物血药水平（如MPA和CNI）有助于确保治疗依从性。 十、根据患者的独特特征和风险特征个体化临床管理 LN的管理较为复杂，因为每个患者都有不同的遗传背景、风险特征、药物药代动力学和药效学以及心理社会视角。LN管理的个体化需要考虑每个患者独特的特征，以决定能够改善短期和长期临床结果的治疗方法。尽管来自临床试验的证据指导了活动性LN的治疗选择，但必须注意这些试验的纳入和排除标准以及患者人口统计学，并在现实世界环境中考虑每个患者的独特特征和独特风险特征。随着贝利尤单抗和CNI等疗效已被证实的治疗方法的增加，以及Obinutuzumab（靶向B淋巴细胞）和Anifrolumab（靶向I型干扰素）等潜在新疗法的发展，将促进临床管理的个体化。 结论 尽管LN仍是一种复杂的疾病，但近年来临床治疗方面的进展为临床管理提供了越来越多的选项和方法。新疗法正在改变LN的治疗格局，一些疗法取得了积极的结果，还有各种针对不同免疫途径的药物正在研究中。通过考虑患者的风险特征并评估独特的临床和肾脏病理特征，可以指导个体化管理和个性化护理，以实现最佳的长期肾脏和患者生存率以及生活质量，同时尽量减少并发症和不良反应（见表1）。 表格1. LN管理十条建议 通过遵循这些建议，临床医生可以更好地管理LN患者，提高治疗效果，改善患者的生活质量，并减少长期并发症的风险。 Selene T Y Teoh, et al. Clin Kidney J . 2024 Nov 22;18(1):sfae376.  声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。 最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！ （来源：《肾医线》编辑部）

ROCKVILLE, Md.& EDMONTON, Alberta--(BUSINESS WIRE)--Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) today announced financial results for the three and six months ended June 30, 2025. Financial Results Total Revenue: For the three and six months ended June 30, 2025, total revenue was $70.0 million and $132.5 million, up 22% and 23%, respectively, from $57.2 million and $107.5 million, respectively, for the same periods of 2024. Net Product Sales: For the three and six months ended June 30, 2025, net product sales of LUPKYNIS, the first FDA-approved oral therapy for the treatment of adult patients with active lupus nephritis, were $66.6 million and $126.5 million, up 21% and 23%, respectively, from $55.0 million and $103.1 million, respectively, for the same periods of 2024. License, Collaboration and Royalty Revenue: For the three and six months ended June 30, 2025, license, collaboration and royalty revenue, which includes manufacturing services revenue from Aurinia’s collaboration partner, Otsuka, was $3.4 million and $5.9 million, up 55% and 34%, respectively, from $2.2 million and $4.4 million, respectively, in the same periods of 2024. Net Product Sales: For the three and six months ended June 30, 2025, net product sales of LUPKYNIS, the first FDA-approved oral therapy for the treatment of adult patients with active lupus nephritis, were $66.6 million and $126.5 million, up 21% and 23%, respectively, from $55.0 million and $103.1 million, respectively, for the same periods of 2024. License, Collaboration and Royalty Revenue: For the three and six months ended June 30, 2025, license, collaboration and royalty revenue, which includes manufacturing services revenue from Aurinia’s collaboration partner, Otsuka, was $3.4 million and $5.9 million, up 55% and 34%, respectively, from $2.2 million and $4.4 million, respectively, in the same periods of 2024. Net Income (Loss): For the three and six months ended June 30, 2025, net income (loss) was $21.5 million and $44.9 million, respectively, compared to $0.7 million and $(10.0) million, respectively, in the same periods of 2024. Cash Flow Provided by (Used in) Operating Activities: For the six months ended June 30, 2025, cash flow provided by (used in) operating activities was $45.5 million, compared to $(2.8) million in the same period of 2024. Excluding $11.5 million of cash payments made in connection with the November 2024 restructuring, cash flow generated from operations was $57.0 million for the six months ended June 30, 2025. Cash Position As of June 30, 2025, Aurinia had cash, cash equivalents, restricted cash and investments of $315.1 million, compared to $358.5 million at December 31, 2024. For the six months ended June 30, 2025, the Company repurchased 11.2 million of its common shares for $90.8 million. The Board has approved an increase to the previously announced share repurchase plan of an additional $150 million of common shares. Purchases under the share repurchase plan, which to date have totaled 18.3 million of its common shares for $138.4 million, began on February 21, 2024. The expiry date of the share repurchase plan is not currently known. This program is being and will continue to be implemented through open market or privately negotiated purchases, including under a plan intended to benefit from the affirmative defense under Rule 10b5-1, Rule 10b-18 or an automatic securities purchase plan, an accelerated share repurchase program, or other mechanisms. The timing and amount of repurchase transactions will be determined by the Company based on its evaluation of market conditions, share price, legal requirements, including applicable blackout period restrictions, and other factors. The purchase price of any common shares will be determined in accordance with applicable U.S. securities laws. The Company is relying on the exemptive relief granted by the Canadian Securities Authorities as described in its February 29, 2024 press release. Full Year 2025 Total Revenue and Net Product Sales Guidance For 2025, Aurinia is increasing total revenue guidance from a range of $250 million to $260 million to a range of $260 million to $270 million and net product sales guidance from a range of $240 million to $250 million to a range of $250 million to $260 million. “We continue to see solid growth for LUPKYNIS, partially driven by the new 2024 American College of Rheumatology lupus nephritis treatment guidelines, which recommend the incorporation of drugs like LUPKYNIS into first-line therapy in order to preserve kidney function,” stated Peter Greenleaf, President and Chief Executive Officer of Aurinia. “Additionally, we are excited about the positive results from our Phase 1 study of aritinercept, a dual inhibitor of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Aritinercept was well tolerated at all dose levels tested and single doses led to robust and long-lasting reductions in immunoglobulins (antibodies). We look forward to initiating clinical studies in at least two autoimmune diseases in the second half of this year.” Webcast & Conference Call Details A webcast and conference call will be hosted today, July 31, at 8:30 a.m. ET. The link to the audio webcast is available here. To join the conference call, please dial 877-407-9170/+1 201-493-6756. A replay of the webcast will be available on Aurinia’s website. About Aurinia Aurinia is a biopharmaceutical company focused on delivering therapies to people living with autoimmune diseases with high unmet medical needs. In January 2021, the Company introduced LUPKYNIS® (voclosporin), the first FDA-approved oral therapy for the treatment of adult patients with active lupus nephritis. Aurinia is also developing aritinercept (AUR200), a dual inhibitor of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) for the potential treatment of autoimmune diseases. Forward-Looking Statements This press release contains forward-looking information within the meaning of applicable Canadian securities law and forward-looking statements within the meaning of applicable U.S. securities law. We caution investors that forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and involve substantial risks and uncertainties that could cause the actual outcomes to differ materially from what we currently expect. These risks and uncertainties include, but are not limited to, those associated with: LUPKYNIS net product sales, the timing of clinical study results and other risks and uncertainties identified in our filings with the U.S. Securities and Exchange Commission. Forward-looking statements in this press release apply only as of the date made, and we undertake no obligation to update or revise any forward-looking statements to reflect subsequent events or circumstances. Additional information related to Aurinia, including a detailed list of the risks and uncertainties affecting Aurinia and its business, can be found in Aurinia’s most recent Annual Report on Form 10-K and its other public available filings available by accessing the Canadian Securities Administrators’ System for Electronic Document Analysis and Retrieval (SEDAR) website at www.sedarplus.ca or the U.S. Securities and Exchange Commission’s Electronic Document Gathering and Retrieval System (EDGAR) website at www.sec.gov/edgar, and on Aurinia’s website at www.auriniapharma.com. AURINIA PHARMACEUTICALS INC. AND SUBSIDIARY CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands) June 30, 2025 December 31, 2024 (Unaudited) ASSETS Current assets: Cash, cash equivalents and restricted cash $ 53,002 $ 83,433 Short-term investments 262,131 275,043 Accounts receivable, net 40,091 36,544 Inventory, net 46,503 39,228 Prepaid expenses and deposits 6,578 11,219 Other current assets 665 1,129 Total current assets 408,970 446,596 Finance right-of-use lease assets 83,195 92,072 Intangible assets, net 4,046 4,355 Operating right-of-use lease assets 3,837 4,068 Property and equipment, net 2,421 2,731 Other noncurrent assets 93 823 Total assets $ 502,562 $ 550,645 LIABILITIES AND SHAREHOLDERS' EQUITY Current liabilities: Accounts payable $ 3,312 $ 5,187 Accrued expenses 49,704 64,971 Finance lease liabilities, current portion 16,167 14,046 Deferred revenue 5,499 11,002 Operating lease liabilities, current portion 1,047 1,026 Other current liabilities 2,537 1,531 Total current liabilities 78,266 97,763 Finance lease liabilities, less current portion 59,282 58,554 Deferred revenue, less current portion 12,349 1,699 Deferred compensation and other noncurrent liabilities 12,030 9,408 Operating lease liabilities, less current portion 5,334 5,743 Total liabilities 167,261 173,167 Shareholders' equity Common shares - no par value, unlimited shares authorized, 132,668 and 140,883 shares issued and outstanding at June 30, 2025 and December 31, 2024, respectively 1,122,582 1,187,696 Additional paid-in capital 105,337 126,999 Accumulated other comprehensive loss (905 ) (647 ) Accumulated deficit (891,713 ) (936,570 ) Total shareholders' equity 335,301 377,478 Total liabilities and shareholders' equity $ 502,562 $ 550,645 AURINIA PHARMACEUTICALS INC. AND SUBSIDIARY CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) (in thousands, except per share data) Three months ended Six months ended June 30, June 30, 2025 2024 2025 2024 Revenue Net product sales $ 66,574 $ 55,028 $ 126,545 $ 103,101 License, collaboration and royalty revenue 3,434 2,164 5,928 4,394 Total revenue 70,008 57,192 132,473 107,495 Operating expenses Cost of revenue 7,115 8,909 15,689 16,661 Selling, general and administrative 26,018 44,934 46,357 92,629 Research and development 7,432 4,080 13,175 9,631 Restructuring 114 1,072 1,647 7,755 Other expense (income), net 9,246 (290 ) 13,675 (4,415 ) Total operating expenses 49,925 58,705 90,543 122,261 Income (loss) from operations 20,083 (1,513 ) 41,930 (14,766 ) Interest income 3,190 4,189 6,759 8,715 Interest expense (1,117 ) (1,198 ) (2,184 ) (2,481 ) Net income (loss) before income taxes 22,156 1,478 46,505 (8,532 ) Income tax expense 643 756 1,648 1,495 Net income (loss) $ 21,513 $ 722 $ 44,857 $ (10,027 ) Earnings (loss) per share Basic $ 0.16 $ 0.01 $ 0.33 $ (0.07 ) Diluted $ 0.16 $ 0.01 $ 0.32 $ (0.07 ) Shares used in computing earnings (loss) per share Basic 134,873 143,327 136,878 143,507 Diluted 137,526 144,110 140,193 143,507 AURINIA PHARMACEUTICALS INC. AND SUBSIDIARY CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited) (in thousands) Six Months Ended June 30, 2025 2024 Cash flows from operating activities: Net income (loss) $ 44,857 $ (10,027 ) Adjustments to reconcile net income (loss) to net cash provided by (used in) operating activities: Share-based compensation 2,031 14,323 Amortization and depreciation 9,720 9,690 Foreign exchange loss (gain) on revaluation of Monoplant finance lease liability 9,265 (5,705 ) Net amortization of premiums and discounts on investments (5,219 ) (6,331 ) Other, net 4,132 919 Net changes in operating assets and liabilities: Accounts receivable, net (3,547 ) (1,433 ) Inventory, net (7,275 ) 852 Prepaid expenses and other current assets 5,106 (4,305 ) Other noncurrent operating assets 730 (12 ) Accounts payable (1,875 ) 4,088 Accrued expenses and other liabilities (17,136 ) (3,805 ) Deferred revenue 5,147 (644 ) Lease liabilities (395 ) (365 ) Net cash provided by (used in) operating activities 45,541 (2,755 ) Cash flows from investing activities: Proceeds from the sale and maturities of investments 255,285 328,877 Purchases of investments (237,411 ) (318,126 ) Purchases of property, equipment and intangible assets (115 ) (140 ) Net cash provided by investing activities 17,759 10,611 Cash flows from financing activities: Repurchase of common shares (89,485 ) (18,435 ) Principal portion of finance lease payments (6,201 ) (6,001 ) Proceeds from issuance of common shares from exercise of stock options and vesting of RSUs and performance awards 10,590 6,134 Proceeds from issuance of common shares under ESPP 401 703 Taxes paid related to net settlement of exercises of stock options and vesting of RSUs and performance awards (9,036 ) (5,725 ) Net cash used in financing activities (93,731 ) (23,324 ) Net decrease in cash, cash equivalents and restricted cash (30,431 ) (15,468 ) Cash, cash equivalents and restricted cash, beginning of the period 83,433 48,875 Cash, cash equivalents and restricted cash, end of the period $ 53,002 $ 33,407