Aliskiren Fumarate

FILSPARI achieved record 993 new PSFs for IgAN in the U.S. in the first quarter; U.S. net product sales grew 88% year over year to $105 million FDA approval in FSGS expands total addressable FILSPARI patient population in the U.S. to more than 100,000; first FSGS patients treated within one week of approval First new patient dosed in restarted Phase 3 HARMONY Study of pegtibatinase; Topline data expected 2H 2027 SAN DIEGO--(BUSINESS WIRE)-- Travere Therapeutics, Inc. (Nasdaq: TVTX) today reported its first quarter 2026 financial results and provided a corporate update. “This has been a transformative start to the year for Travere, highlighted by the landmark approval of FILSPARI in FSGS, record demand that reinforces FILSPARI’s foundational position in IgAN, and the advancement of pegtibatinase with the first new patient dosed in the restarted Phase 3 HARMONY study,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “With FILSPARI now positioned to help more than 100,000 patients across IgAN and FSGS, we see a substantial and durable growth opportunity ahead, supporting a compelling long-term trajectory for the Company.” Financial Results for the Quarter Ended March 31, 2026 U.S. net product sales for the first quarter of 2026 were $124.5 million, compared to $75.9 million for the same period in 2025. The increase is attributable to growth in sales of FILSPARI. Research and development (R&D) expenses for the first quarter of 2026 were $57.1 million, compared to $46.9 million for the same period in 2025. The increase is primarily attributable to the restart of the Phase 3 HARMONY Study of pegtibatinase in classical HCU. On a non-GAAP adjusted basis, R&D expenses were $51.5 million for the first quarter of 2026, compared to $42.2 million for the same period in 2025. Selling, general, and administrative (SG&A) expenses for the first quarter of 2026 were $80.3 million, compared to $60.4 million for the same period in 2025. The difference is largely attributable to investments in preparing for FILSPARI’s launch in FSGS as well as commercial investments in IgAN. On a non-GAAP adjusted basis, SG&A expenses were $69.3 million for the first quarter of 2026, compared to $53.3 million for the same period in 2025. Total other income, net for the first quarter of 2026 was $0.2 million, compared to $1.5 million for the same period in 2025. Net loss for the first quarter of 2026 was $37.1 million, or $0.40 per basic share, compared to a net loss of $41.2 million, or $0.47 per basic share for the same period in 2025. On a non-GAAP adjusted basis, net income for the first quarter of 2026 was $4.1 million, or $0.05 per basic share, compared to a net loss of $16.9 million, or $0.19 per basic share for the same period in 2025. As of March 31, 2026, the Company had cash, cash equivalents, and marketable securities of $264.7 million. This amount does not include the $25 million sales-based milestone from Mirum Pharmaceuticals, which was recognized in 2025 and received in April 2026. Program Updates FILSPARI® (sparsentan) – IgA Nephropathy (IgAN) 993 new patient start forms (PSFs) were received during the first quarter, driven by continued demand from new and repeat prescribers. U.S. net product sales of FILSPARI totaled $105.2 million in the first quarter of 2026, representing 88% growth versus the first quarter of 2025. The SPARX Study evaluating FILSPARI in post-transplant patients with recurrent IgAN or FSGS is on track to complete enrollment in the second quarter of 2026. At the National Kidney Foundation (NKF) Spring Clinical Meeting (May 7-10), the Company will present real-world data on combination treatment with FILSPARI and SGLT2 inhibitors in IgAN. In 2026, the Company’s partner, Chugai Pharmaceutical, expects to submit a New Drug Application for sparsentan in Japan. Travere remains eligible to receive milestone payments related to the sparsentan regulatory process and net sales achievements in licensed territories, as well as tiered royalties. FILSPARI® (sparsentan) – Focal Segmental Glomerulosclerosis (FSGS) On April 13, 2026, the U.S. Food and Drug Administration (FDA) approved FILSPARI to reduce proteinuria in adult and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome. Patients with FSGS without nephrotic syndrome span across types of FSGS and represent a population aligned with the KDIGO guidelines for treating glomerular diseases. Nephrotic syndrome is commonly defined as the presence of three concurrent criteria: proteinuria greater than 3.5 g/24h, edema, and albumin less than 3.0 g/dL. FILSPARI is the first and only FDA-approved medicine for FSGS, with an estimated addressable population in the U.S. of more than 30,000 patients without nephrotic syndrome. The Company received its first FSGS patient start forms on the first day following approval, with reimbursed FILSPARI treatments initiated within the first week of approval. At the NKF Spring Clinical Meeting (May 7–10), the Company will present additional Phase 3 DUPLEX data, including results from patients who switched from irbesartan to FILSPARI in the open-label extension. Pegtibatinase (TVT-058) – Classical Homocystinuria (HCU) In the first quarter of 2026, the Company restarted enrollment activities in the pivotal Phase 3 HARMONY Study of pegtibatinase for the treatment of HCU. The study is expected to enroll approximately 70 patients aged 12 to 65 with plasma total homocysteine (tHcy) levels ≥50 µM. The primary endpoint is change from baseline in plasma tHcy levels, averaged across weeks 6 through 12, in patients receiving pegtibatinase compared with those receiving placebo, with durability of response through Week 24 as a key secondary endpoint. In April 2026, the Company dosed the first new patient following the study restart, with topline data anticipated in 2H 2027. Pegtibatinase has the potential to become the first and only disease-modifying therapy for people living with HCU. Conference Call Information Travere Therapeutics will host a conference call and webcast today, May 4, 2026, at 4:30 p.m. ET to discuss company updates and first quarter 2026 financial results. To participate in the conference call, dial +1 (833) 461-5787 (U.S.) or +1 (585) 542-9983 (International), meeting ID 293685046 shortly before 4:30 p.m. ET. The webcast can be accessed on the Investor page of Travere’s website at ir.travere.com/events-presentations. Following the live webcast, an archived version of the call will be available for 30 days on the Company’s website. Use of Non-GAAP Financial Measures To supplement Travere’s financial results and guidance presented in accordance with U.S. generally accepted accounting principles (GAAP), the Company uses certain non-GAAP adjusted financial measures in this press release and the accompanying tables. The Company believes that these non-GAAP financial measures are helpful in understanding its past financial performance and potential future results. They are not meant to be considered in isolation or as a substitute for comparable GAAP measures and should be read in conjunction with the consolidated financial statements prepared in accordance with GAAP. Travere’s management regularly uses these supplemental non-GAAP financial measures internally to understand, manage and evaluate its business and make operating decisions. In addition, Travere believes that the use of these non-GAAP measures enhances the ability of investors to compare its results from period to period and allows for greater transparency with respect to key financial metrics the Company uses in making operating decisions. Investors should note that these non-GAAP financial measures are not prepared under any comprehensive set of accounting rules or principles and do not reflect all of the amounts associated with the Company’s results of operations as determined in accordance with GAAP. Investors should also note that these non-GAAP financial measures have no standardized meaning prescribed by GAAP and, therefore, have limits in their usefulness to investors. In addition, from time to time in the future the Company may exclude other items, or cease to exclude items that it has historically excluded, for purposes of its non-GAAP financial measures; because of the non-standardized definitions, the non-GAAP financial measures as used by the Company in this press release and the accompanying tables may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by the Company’s competitors and other companies. As used in this press release, (i) the historical non-GAAP net income (loss) measures exclude from GAAP net income (loss), as applicable, stock-based compensation expense, amortization and depreciation expense, and income tax; (ii) the historical non-GAAP SG&A expense measures exclude from GAAP SG&A expenses, as applicable, stock-based compensation expense, and amortization and depreciation expense; (iii) the historical non-GAAP R&D expense measures exclude from GAAP R&D expenses, as applicable, stock-based compensation expense, and amortization and depreciation expense; (iv) royalty expense excludes amortization expense. About Travere Therapeutics At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com. FILSPARI® (sparsentan) U.S. Indication FILSPARI® (sparsentan) is indicated: To slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. To reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome. IMPORTANT SAFETY INFORMATION BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITY Because of the risk of hepatotoxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients and pharmacies must enroll in the program. Hepatotoxicity Some Endothelin Receptor Antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. In clinical studies, elevations in aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal (ULN) have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. Measure transaminases and bilirubin before initiating treatment and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3x ULN. FILSPARI should generally be avoided in patients with elevated aminotransferases (>3x ULN) at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity. Embryo-Fetal Toxicity FILSPARI is contraindicated for use during pregnancy because it may cause fetal harm if used by pregnant patients. Therefore, in patients who can become pregnant, exclude pregnancy prior to initiation of FILSPARI. Advise use of effective contraception before the initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with FILSPARI. When pregnancy is detected, discontinue FILSPARI as soon as possible. Contraindications FILSPARI is contraindicated in patients who are pregnant. Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren. Warnings and Precautions Hepatotoxicity: Elevations in ALT or AST of at least 3-fold ULN have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. While no concurrent elevations in bilirubin >2-times ULN or cases of liver failure were observed in FILSPARI-treated patients in clinical trials, some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and then every 3 months during treatment. Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with FILSPARI and seek medical attention. If aminotransferase levels are abnormal at any time during treatment, interrupt FILSPARI and monitor as recommended. Consider re-initiation of FILSPARI only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity. Avoid initiation of FILSPARI in patients with elevated aminotransferases (>3x ULN) because monitoring hepatotoxicity in these patients may be more difficult and these patients may be at increased risk for serious hepatotoxicity. FILSPARI REMS: Due to the risk of hepatotoxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Prescribers, patients, and pharmacies must be enrolled in the REMS program and comply with all requirements ( www.filsparirems.com). Embryo-Fetal Toxicity: Based on data from animal reproduction studies, FILSPARI may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of fetal harm related to the use of FILSPARI. Counsel patients who can become pregnant of the potential risk to a fetus. Exclude pregnancy before initiating treatment with FILSPARI. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with FILSPARI. Advise pre-pubertal females and/or their guardian(s) of the fetal risk and the need to use effective contraception once they reach reproductive potential. When pregnancy is detected, discontinue FILSPARI as soon as possible. Hypotension: Hypotension has been observed in patients treated with ARBs and ERAs and was observed in FILSPARI clinical studies. There was a greater incidence of hypotension-associated adverse events, some serious, including dizziness, in patients treated with FILSPARI compared to irbesartan. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. If hypotension develops, despite elimination or reduction of other antihypertensive medications, consider a dose reduction or dose interruption of FILSPARI. A transient hypotensive response is not a contraindication to further dosing of FILSPARI, which can be given once blood pressure has stabilized. Acute Kidney Injury: Monitor kidney function periodically. Drugs that inhibit the renin-angiotensin system (RAS) can cause kidney injury. Patients whose kidney function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute kidney injury on FILSPARI. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function while on FILSPARI. Hyperkalemia: Monitor serum potassium periodically and treat appropriately. Patients with advanced kidney disease, taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia. Dosage reduction or discontinuation of FILSPARI may be required. Fluid Retention: Fluid retention may occur with ERAs and has been observed in clinical studies with FILSPARI. FILSPARI has not been evaluated in patients with heart failure. If clinically significant fluid retention develops, evaluate the patient to determine the cause and the potential need to initiate or modify the dose of diuretic treatment then consider modifying the dose of FILSPARI. Adverse Reactions IgAN patients receiving FILSPARI: The most common adverse reactions (≥5%) are hyperkalemia, hypotension (including orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney injury. FSGS patients receiving FILSPARI: The most common adverse reactions (≥5%) are peripheral edema, hypotension (including orthostatic hypotension), hyperkalemia, dizziness, and anemia. Drug Interactions Renin-Angiotensin System (RAS) Inhibitors and ERAs: Do not coadminister FILSPARI with ARBs, ERAs, or aliskiren due to increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure). Strong and Moderate CYP3A Inhibitors: Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. If a strong CYP3A inhibitor cannot be avoided, interrupt FILSPARI treatment. When resuming treatment with FILSPARI, consider dose titration. Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors. Concomitant use with a strong CYP3A inhibitor increases sparsentan exposure which may increase the risk of FILSPARI adverse reactions. Strong CYP3A Inducers: Avoid concomitant use with a strong CYP3A inducer. Concomitant use with a strong CYP3A inducer decreases sparsentan exposure which may reduce FILSPARI efficacy. Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of worsening renal function with concomitant use with NSAIDs (including selective COX-2 inhibitors). In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, concomitant use of NSAIDs (including selective COX-2 inhibitors) with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure. These effects are usually reversible. CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. Sparsentan is a weak inducer of CYP2B6 and 2C9, and a moderate inducer of 2C19. Sparsentan decreases exposure of these substrates, which may reduce efficacy related to these substrates. P-gp Substrates: Monitor for adverse reactions and consider dose reduction of P-gp substrates with narrow therapeutic indices when co-administered with FILSPARI. FILSPARI is a weak P-gp inhibitor and may increase plasma concentrations of P-gp substrate drugs. Agents Increasing Serum Potassium: Monitor serum potassium frequently in patients treated with FILSPARI and other agents that increase serum potassium. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia. Please see the full Prescribing Information, including BOXED WARNING, for additional Important Safety Information. Forward-Looking Statements This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “on-track,” “positioned,” “look forward to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,” “plans,” “expects,” “intends,” “potential,” or similar expressions. In addition, expressions of strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to: continued progress with FILSPARI in IgAN; statements and expectations regarding FILSPARI’s foundational position in IgAN; estimates regarding the commercial opportunity for FILSPARI; statements and expectations regarding the substantial and durable growth opportunity ahead, supporting a compelling long-term trajectory for the Company; statements and expectations regarding the commercial launch of FILSPARI in FSGS; statements and expectations regarding the Company’s pivotal Phase 3 HARMONY Study, including expectations regarding the timing and outcome thereof; statements regarding the potential for pegtibatinase to become the first and only disease-modifying therapy for people living with HCU; statements and expectations regarding the other clinical studies and data described herein; statements and expectations regarding potential milestone and royalty payments and the potential achievement and timing thereof; statements and expectations regarding the activities of the Company’s partners and collaborators; statements related to the estimated sizes of patient populations; and statements regarding financial metrics and expectations related thereto. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties related to the Company’s business and finances in general, the success of its commercial products, risks and uncertainties associated with its preclinical and clinical stage pipeline, risks and uncertainties associated with the regulatory review and approval process, risks and uncertainties associated with enrollment of clinical trials for rare diseases, and risks that ongoing or planned clinical trials may not succeed or may be delayed for safety, regulatory or other reasons. Specifically, the Company faces risks associated with the commercial launch of FILSPARI in FSGS and commercial investments in IgAN, the timing and potential outcome of its and its partners’ clinical studies, market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, risks related to the challenges of manufacturing scale-up, risks associated with the successful development and execution of commercial strategies for such products, including FILSPARI, and risks and uncertainties related to the current administration, including but not limited to risks and uncertainties related to tariffs and the funding, staffing and prioritization of resources at government agencies including the FDA. The Company also faces the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company’s products, and technological changes that may limit demand for the Company’s products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. TRAVERE THERAPEUTICS, INC. CONSOLIDATED BALANCE SHEETS (in thousands, except share amounts) March 31, 2026 December 31, 2025 Assets (unaudited) Current assets: Cash and cash equivalents $ 78,362 $ 93,035 Marketable debt securities, at fair value 186,314 229,761 Accounts receivable, net 87,302 80,134 Inventory 6,356 5,875 Prepaid expenses and other current assets 34,347 28,760 Total current assets 392,681 437,565 Long-term inventory 30,698 30,280 Property and equipment, net 3,627 4,022 Operating lease right of use assets 9,668 10,576 Intangible assets, net 110,038 113,868 Other assets 8,476 8,880 Total assets $ 555,188 $ 605,191 Liabilities and Stockholders' Equity Current liabilities: Accounts payable $ 12,912 $ 24,800 Accrued expenses 104,408 126,035 Operating lease liabilities, current portion 6,017 5,875 Other current liabilities 2,100 3,194 Total current liabilities 125,437 159,904 Convertible debt 312,079 311,724 Operating lease liabilities, less current portion 9,566 11,134 Other non-current liabilities 9,378 7,601 Total liabilities 456,460 490,363 Stockholders' Equity: Preferred stock $0.0001 par value; 20,000,000 shares authorized; 0 issued and outstanding as of March 31, 2026 and December 31, 2025 — — Common stock $0.0001 par value; 200,000,000 shares authorized; 92,403,744, and 90,922,868 issued and outstanding as of March 31, 2026 and December 31, 2025, respectively 9 9 Additional paid-in capital 1,609,596 1,588,721 Accumulated deficit (1,509,815 ) (1,472,713 ) Accumulated other comprehensive loss (1,062 ) (1,189 ) Total stockholders' equity 98,728 114,828 Total liabilities and stockholders' equity $ 555,188 $ 605,191 Note: Certain adjustments / reclassifications have been made to prior periods to conform to current year presentation. TRAVERE THERAPEUTICS, INC. CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except share and per share data) (unaudited) Three Months Ended March 31, 2026 2025 Net product sales: FILSPARI $ 105,152 $ 55,881 Tiopronin products 19,340 19,980 Total net product sales 124,492 75,861 License and collaboration revenue 2,707 5,871 Total revenue 127,199 81,732 Operating expenses: Cost of goods sold 1,950 4,679 Research and development 57,094 46,889 Selling, general and administrative 80,254 60,413 Royalty expense 24,816 12,425 Total operating expenses 164,114 124,406 Operating loss (36,915 ) (42,674 ) Other income, net: Interest income 2,584 3,795 Interest expense (2,300 ) (2,857 ) Other (expense) income, net (91 ) 549 Total other income, net 193 1,487 Loss from continuing operations before income tax (36,722 ) (41,187 ) Income tax benefit (provision) on continuing operations 120 (39 ) Loss from continuing operations, net of tax (36,602 ) (41,226 ) Loss from discontinued operations, net of tax (500 ) — Net loss $ (37,102 ) $ (41,226 ) Per share data: Net loss per common share $ (0.40 ) $ (0.47 ) Weighted average common shares outstanding 91,868,862 88,355,973 Note: Certain adjustments / reclassifications have been made to prior periods to conform to current year presentation. TRAVERE THERAPEUTICS, INC. RECONCILIATION OF GAAP REPORTED TO NON-GAAP ADJUSTED INFORMATION (in thousands, except share and per share data) (unaudited) Three Months Ended March 31, 2026 2025 GAAP operating loss $ (36,915 ) $ (42,674 ) R&D operating expense (57,094 ) (46,889 ) Stock compensation 5,558 4,726 Non-GAAP R&D expense (51,536 ) (42,163 ) SG&A operating expense (80,254 ) (60,413 ) Stock compensation 10,588 6,766 Depreciation 396 377 Subtotal non-GAAP items 10,984 7,143 Non-GAAP SG&A expense (69,270 ) (53,270 ) Royalty expense (24,816 ) (12,425 ) Amortization 24,816 12,425 Non-GAAP royalty expense — — Subtotal non-GAAP items 41,358 24,294 Non-GAAP operating income (loss) $ 4,443 $ (18,380 ) GAAP net loss $ (37,102 ) $ (41,226 ) Non-GAAP operating adjustments 41,358 24,294 Income tax (benefit) provision (120 ) 39 Non-GAAP net income (loss) $ 4,136 $ (16,893 ) Per share data: Net income (loss) per common share $ 0.05 $ (0.19 ) Weighted average common shares outstanding 91,868,862 88,355,973 Note: Certain adjustments / reclassifications have been made to prior periods to conform to current year presentation. Investors: 888-969-7879 ir@travere.com Media: 888-969-7879 mediarelations@travere.com

摘要 高血压作为全球范围内最常见的心血管疾病危险因素之一，其有效控制对于预防心脑血管事件具有重要意义。近年来，随着药理学和分子生物学的发展，高血压的药物治疗取得了显著进展。本文基于Web of Science、Scopus及Google Scholar数据库的最新文献，系统综述了高血压药物治疗的最新进展，包括传统药物的新适应症、作用机制的深入解析、新型药物的研发及个体化治疗策略的发展。旨在为临床医生和研究人员提供参考，推动高血压治疗的精准化和个体化。 关键词 ：高血压；药物治疗；新药；RAAS抑制剂；个体化治疗 1. 引言 高血压是导致心脑血管疾病的主要危险因素，全球患病人数超过10亿，且呈逐年上升趋势[1]。高血压不仅显著增加中风、冠心病、心力衰竭和肾脏疾病的风险，还给公共卫生带来巨大负担。尽管已有多种降压药物应用于临床，但仍有大量患者血压控制不达标，且存在耐药性和药物副作用问题[2]。因此，探索高血压药物治疗的新机制、新药物及优化治疗方案成为研究热点。本文通过检索Web of Science、Scopus和Google Scholar数据库，结合近5年高影响力文献，综述高血压药物治疗的最新进展。 2. 传统降压药物的进展 2.1 血管紧张素转换酶抑制剂（ACEI）与血管紧张素Ⅱ受体拮抗剂（ARBs） ACEI和ARBs作为抑制RAAS系统的核心药物，广泛应用于高血压及相关心肾保护[3]。最新研究表明，ARBs不仅通过阻断AT1受体降低血压，还具有抗炎、抗纤维化作用，有助于改善心脏重构和延缓肾功能恶化[4]。ACEI则因其增加血管舒张因子（如缓激肽）水平，展现出对代谢综合征患者的保护作用[5]。此外，ACEI/ARBs在糖尿病肾病、高血压合并心衰等特殊人群中的应用也得到进一步验证。 2.2 钙通道阻滞剂（CCBs） CCBs通过阻断钙离子进入血管平滑肌细胞，降低血管张力，达到降压效果。新一代长效CCBs如氨氯地平不仅延长药效时间，减少血压波动，还降低了心血管事件风险[6]。复合制剂的开发（如CCB与ACEI/ARB的固定剂量复合制剂）显著提高了患者依从性和疗效[7]。此外，部分CCBs对心率影响较小，适用于心功能不全患者。 2.3 利尿剂 传统利尿剂如噻嗪类仍是控制高血压的基础药物，尤其在老年患者和盐敏感性高血压中疗效显著[8]。近年来，研究聚焦于低剂量联合用药，旨在减少电解质紊乱和代谢副作用。同时，新型选择性利尿剂（如吲达帕胺）因其对心血管保护作用更佳而受到关注。 2.4 β受体阻滞剂 β阻滞剂在高血压治疗中的地位有所下降，主要因其对代谢的不利影响及对老年患者疗效有限[9]。然而，对于合并心力衰竭、冠心病及某些心律失常患者，β阻滞剂仍不可替代。新型β阻滞剂如nebivolol除传统的β1受体阻断外，还具有促进一氧化氮释放的血管扩张作用，显示出良好的疗效和耐受性[10]。 3. 新型降压药物的研发进展 3.1 直接肾素抑制剂 阿利斯特龙（Aliskiren）是首个口服直接肾素抑制剂，通过阻断RAAS系统最初环节发挥降压作用。临床试验显示其在部分患者中对血压控制有额外益处，但与ACEI/ARB合用时需警惕高钾血症和肾功能损害风险[11]。因此，目前主要用于单药治疗或特定患者群体。 3.2 促钠尿肽系统激动剂 促钠尿肽系统在调节血压和体液平衡中起重要作用。新型药物如sacubitril/valsartan（ARNI）通过抑制中性内肽酶和阻断AT1受体，增强内肽系统的利尿、扩血管和抗纤维化作用，显示出优于传统药物的心肾保护效果，尤其在心衰患者中获益显著[12]。 3.3 钠-葡萄糖共转运蛋白2抑制剂（SGLT2i） SGLT2i最初用于糖尿病治疗，但其通过促进钠排泄和降低血容量的机制展现出降压作用[13]。在伴有糖尿病和心衰的高血压患者中，SGLT2i不仅降低血压，还显著减少心肾事件，成为多学科关注的新兴治疗选择。 3.4 选择性钠通道抑制剂 选择性钠通道抑制剂通过调节肾小管钠重吸收，降低血容量，从而发挥降压作用[14]。目前处于早期研究阶段，未来有望成为高血压治疗的新靶点。 4. 个体化治疗策略的发展 4.1 基因组学与药物基因组学 基因多态性显著影响降压药物的代谢、疗效及副作用。药物基因组学的发展使得个体化用药成为可能。例如，CYP450酶系的遗传变异指导β阻滞剂和CCBs的剂量调整，显著提高疗效并减少不良反应[15]。未来，基因检测或将成为高血压治疗前的常规评估。 4.2 大数据与人工智能辅助决策 基于大数据的患者特征分析和人工智能（AI）模型预测，有助于优化降压方案，提高疗效和安全性[16]。AI可以整合患者基因、生活习惯、合并症等多维信息，辅助临床决策，实现精准治疗。 4.3 联合用药和固定剂量复合制剂 联合用药是当前控制难治性高血压的主要策略。固定剂量复合制剂的应用不仅提高了患者依从性，还减少了药物相互作用风险[17]。未来复合制剂将更加多样化，涵盖多靶点药物，满足个体化需求。 5. 未来展望 高血压药物治疗正朝着多靶点、多机制联合干预方向发展。新药研发结合精准医学、基因编辑技术及新型给药系统（如纳米载体、长效控释制剂），将极大提升治疗效果和患者生活质量。此外，生活方式干预与药物治疗的整合管理也将成为未来的重要方向。跨学科合作、患者教育及数字健康工具的推广将促进高血压管理的整体优化。 6. 结论 近年来，高血压药物治疗学取得显著进展，传统药物的优化与新型药物的开发相辅相成，个体化治疗策略逐步推广。未来，随着基础研究与临床应用的深入结合，高血压的药物治疗将更加精准和高效，为患者带来更大获益。 参考文献 Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16(4):223-237. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA Hypertension Guideline. Hypertension. 2018;71(6):e13-e115. Burnier M. Angiotensin II type 1 receptor blockers. Circulation. 2001;103(6):904-912. Schmieder RE. End organ damage in hypertension. Dtsch Arztebl Int. 2010;107(49):866-873. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting–enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153. Messerli FH, Grossman E, Goldbourt U. Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? JAMA. 1998;279(23):1903-1907. Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents. Hypertension. 2010;55(3):399-407. Ernst ME, Carter BL, Goerdt CJ, et al. Diuretic therapy for hypertension. Am J Hypertens. 2006;19(3):237-242. Bangalore S, Messerli FH, Kostis JB, et al. Cardiovascular protection using beta-blockers. J Am Coll Cardiol. 2007;50(7):563-572. Frishman WH. Nebivolol: a third-generation beta-blocker. J Clin Hypertens (Greenwich). 2007;9(11):850-855. Parving HH, Brenner BM, McMurray JJ, et al. Aliskiren in patients with type 2 diabetes and nephropathy. N Engl J Med. 2008;358(23):2433-2446. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes. Circulation. 2019;139(22):2528-2536. Ellison DH. Selective sodium channel blockers in hypertension. Hypertension. 2015;66(2):214-220. Johnson JA. Pharmacogenetics in hypertension management. Curr Opin Cardiol. 2012;27(4):395-401. Krittanawong C, Johnson KW, Rosenson RS, et al. Deep learning for cardiovascular medicine: a practical primer. Eur Heart J. 2019;40(25):2058-2073. Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents. Hypertension. 2010;55(3):399-407.