Gemfibrozil

Patients with MASH/NASH treated with Rezdiffra experienced clinically meaningful and statistically significant improvements in emotional well-being and health distressStudy results underscore the positive tolerability profile of Rezdiffra CONSHOHOCKEN, Pa., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH), today announced the publication of positive patient-reported outcomes data demonstrating Rezdiffra (resmetirom) improved health-related quality of life (HRQL) in patients with NASH with moderate to advanced fibrosis. The results were published in the journal Hepatology. Rezdiffra is a once-daily, oral, liver-directed thyroid hormone receptor (THR)-β agonist designed to target key underlying causes of NASH. It is the first FDA-approved medication for the treatment of NASH. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and NASH resolution primary endpoints, and 80% of patients treated with Rezdiffra 100 mg experienced improvement or stabilization of fibrosis. Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials. Zobair M. Younossi, M.D., MPH, FACP, FACG, AGAF, FAASLD, Professor and Chairman of the Beatty Liver and Obesity Research Program, Inova Health System, the Chairman of the Global NASH Council and lead author of the HRQL analysis stated, “The serious burden of NASH on patient quality of life remains poorly understood and underappreciated by the health system. NASH is associated with significant impairment of HRQL related to fatigue, lack of stamina and other symptoms. Therefore, these results demonstrating that Rezdiffra helped patients achieve clinically meaningful and statistically significantly improvements in multiple domains of HRQL are highly encouraging. Additionally, we found no worsening of HRQL related to potential side effects of Rezdiffra in the MAESTRO-NASH study, which underscores the tolerability profile of the medication.” In the study, changes in HRQL scores from baseline were evaluated in patients receiving Rezdiffra versus placebo and compared between patients with and without biopsy response. By weeks 24 and 52, patients receiving both doses of Rezdiffra experienced improvement of HRQL scores in the Worry domain of the Chronic Liver Disease Questionnaire-NASH. At week 52, Rezdiffra-treated patients who achieved fibrosis improvement or NASH resolution experienced improvement in several HRQL domains, including domains for Worry, Health Distress and Stigma. The improvement in HRQL among Rezdiffra biopsy responders was contrasted by no similar improvement in the placebo group. Biopsy responders with stage F3 fibrosis at baseline had similar or more pronounced improvements of HRQL in comparison to those responders with F2 or F1B fibrosis at baseline. Bill Sibold, Chief Executive Officer of Madrigal, stated, “NASH is the leading cause of liver transplant among women and those who get listed for hepatocellular carcinoma in the U.S. and the unpredictable speed of NASH disease progression can cause serious emotional distress for people living with the disease. In addition to the health burden of NASH, patient advocates frequently tell us they worry about the impact of the disease on their families and plans for the future. The introduction of Rezdiffra as the first FDA-approved therapy for NASH has provided hope for patients, and we see this demonstrated in the improvements in health-related quality of life observed in the MAESTRO-NASH trial.” About NASH Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NASH is a leading cause of liver-related mortality and an increasing burden on healthcare systems globally. Additionally, patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality. Once patients progress to NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically. NASH is rapidly becoming the leading cause of liver transplantation in the U.S. and is already the leading cause in women. Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., of which approximately 525,000 have NASH with moderate to advanced liver fibrosis. Madrigal plans to focus on approximately 315,000 diagnosed patients with NASH with moderate to advanced liver fibrosis under the care of the liver specialist physicians during the launch of Rezdiffra. NASH is also known as metabolic dysfunction associated steatohepatitis (MASH). In 2023, global liver disease medical societies and patient groups came together to rename the disease, with the goal of establishing an affirmative, non-stigmatizing name and diagnosis. Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction-associated steatotic liver disease (MASLD); NASH was renamed MASH; and an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. In addition to liver disease, patients with MASH have at least one related comorbid condition (e.g., obesity, hypertension, dyslipidemia, or type 2 diabetes). About Rezdiffra What is Rezdiffra? Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It is not known if Rezdiffra is safe and effective in children (under 18 years old). This indication is approved based on improvement of NASH and liver scarring (fibrosis). There are ongoing studies to confirm the clinical benefit of Rezdiffra. Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you: have any liver problems other than NASH.have gallbladder problems or have been told you have gallbladder problems, including gallstones.are pregnant or plan to become pregnant. It is not known if Rezdiffra will harm your unborn baby.are breastfeeding or plan to breastfeed. It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Rezdiffra. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Rezdiffra and other medicines may affect each other, causing side effects. Rezdiffra may affect the way other medicines work, and other medicines may affect how Rezdiffra works.Especially tell your healthcare provider if you take medicines that contain gemfibrozil to help lower your triglycerides, or cyclosporine to suppress your immune system, because Rezdiffra is not recommended in patients taking these medicines.Tell your healthcare provider if you are taking medicines such as clopidogrel to thin your blood or statin medicines to help lower your cholesterol.Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. What are the possible side effects of Rezdiffra? Rezdiffra may cause serious side effects, including: liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, nausea, vomiting, fever, rash, your skin or the white part of your eyes turns yellow (jaundice), pain or tenderness in the upper middle or upper right area of your stomach (abdomen).gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH and may occur if you take Rezdiffra. Call your healthcare provider right away if you develop any signs or symptoms of these conditions including nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting. The most common side effects of Rezdiffra include: diarrhea, nausea, itching, stomach (abdominal) pain, vomiting, dizziness, constipation. These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Madrigal at 1-800-905-0324. Please see the full Prescribing Information, including Patient Information, for Rezdiffra. About Madrigal PharmaceuticalsMadrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of NASH. For more information, visit www.madrigalpharma.com. Forward Looking StatementsThis press release includes “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on Madrigal’s beliefs and assumptions and on information currently available to it but are subject to factors beyond its control. Forward-looking statements reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events. Forward-looking statements include all statements that are not historical facts; statements referenced by forward-looking statement identifiers; and statements regarding: Rezdiffra (resmetirom) and its expected use for treating NASH with moderate to advanced fibrosis. Forward-looking statements can be identified by terms such as “accelerate,” “achieve,” “allow,” “anticipates,” “appear,” “be,” “believes,” “can,” “confidence,” “continue,” “could,” “demonstrates,” ”design,” “estimates,” “expectation,” “expects,” “forecasts,” “future,” “goal,” “help,” “hopeful,” “inform,” “intended,” “intends,” “may,” “might,” “on track,” “planned,” “planning,” “plans,” “positions,” “potential,” “powers,” “predicts,” ”predictive,” “projects,” “seeks,” “should,” “will,” “will achieve,” “will be,” “would”, “future” or similar expressions and the negatives of those terms. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: the assumptions underlying the forward-looking statements; risks of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercial launch of a new product, particularly for a company that does not have commercial experience; risks associated with meeting the objectives of Madrigal’s clinical studies, including, but not limited to Madrigal’s ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for Madrigal’s studies; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the effects of Rezdiffra’s (resmetirom’s) mechanism of action; enrollment and trial conclusion uncertainties; market demand for and acceptance of our product; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financings on terms similar to those arranged in the past; the ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive studies; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; the timing and outcomes of clinical studies of Rezdiffra (resmetirom); the uncertainties inherent in clinical testing; and uncertainties concerning analyses or assessments outside of a controlled clinical trial. Undue reliance should not be placed on forward looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal’s submissions filed with the U.S. Securities and Exchange Commission, or SEC, for more detailed information regarding these risks and uncertainties and other factors that may cause actual results to differ materially from those expressed or implied. Madrigal specifically discusses these risks and uncertainties in greater detail in the sections appearing in Part I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on February 28, 2024, , and Part II, Item 1A of its Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC on August 7, 2024, and as updated from time to time by Madrigal’s other filings with the SEC. Investor Contact Tina Ventura, IR@madrigalpharma.com Media ContactChristopher Frates, media@madrigalpharma.com

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--( BUSINESS WIRE )--United Therapeutics Corporation (Nasdaq: UTHR ), a public benefit corporation, today announced that five presentations and one poster across its commercial and development portfolio will be presented at the CHEST 2024 Annual Meeting hosted by the American College of Chest Physicians taking place October 6-9, 2024, in Boston. United Therapeutics will sponsor the Tyvaso DPI®: Clinical Pearls and Drug-Device Characteristics Symposium . In addition, United Therapeutics is proud to sponsor the Women in Chest Medicine Annual Luncheon and the Advanced Practice Providers ( APPs ) in Chest Medicine Forum. “The CHEST Annual Meeting remains an important event for United Therapeutics and the pulmonary hypertension community, and this year we are excited to share additional analyses, particularly from the BREEZE open-label extension study, that continue to expand on these important learnings,” said Andrew Nelsen, PharmD , Vice President, Global Medical Affairs at United Therapeutics. “Equally, we are proud to sponsor a symposium entitled Tyvaso DPI®: Clinical Pearls and Drug-Device Characteristics , as well as a series of rapid-fire presentations showing interesting findings in health care resource utilization, patient reported outcomes, and health-related qualify of life.” Oral Presentations include: Rapid fire original investigation presentation , Tuesday, October 8, 10:20 a.m. to 10:24 a.m. ET: Rapid Area 4B/4071 – Patient-Reported Symptom Burden and Health-Related Quality of Life in Pulmonary Arterial Hypertension: Results from a Patient’s Perspective on Palliative Care Online Survey . Presented by Denise Sese, M.D., Medical University of South Carolina. Rapid fire original investigation presentation , Tuesday, October 8, 10:32 a.m. to 10:36 a.m. ET: Rapid Area 4B/4071 – Initial Validation of the Pulmonary Hypertension Functional Classification Self-Report (PH-FC-SR): A Patient Focused Measure for Use in Research and in the Clinic . Presented by Kristin Highland, M.D., FCCP, Cleveland Clinic. Rapid fire original investigation presentation , Tuesday, October 8, 1:45 p.m. to 1:49 p.m. ET: Rapid Area 4A/4072 – Real-World Hospitalization Differences in Patients with Pulmonary Hypertension due to Interstitial Lung Disease: Initiating Inhaled Treprostinil vs. Those Who Remain Untreated . Presented by Steven Cassady, M.D., University of Maryland Medical Center. Rapid fire original investigation presentation , Tuesday, October 8, 2:03 p.m. to 2:07 p.m. ET: Rapid Area 4A/4072 – Long-Term Outcomes and Dosing in the BREEZE Study Optional Extension Phase . Presented by Abubakr Bajwa, MBBS, FCCP, Mayo Clinic. Rapid fire original investigation presentation , Tuesday, October 8, 2:21 p.m. to 2:25 p.m. ET: Rapid Area 4A/4072 – Inhaled Treprostinil for the Treatment of Connective Tissue-Associated Pulmonary Arterial Hypertension . Presented by Kristin Highland, M.D., FCCP, Cleveland Clinic. Posters include: Poster discussion session , Wednesday, October 9, 10:20 a.m. to 11:05 a.m. ET: 4529/4430 – Real-World Oral Treprostinil Initiations: Insights from Specialty Pharmacy Data . Presented by Daniel Lachant, D.O., University of Rochester Medical Center. Sponsored events include: The APPs in Chest Medicine Forum , Sunday, October 6, 12:00 to 1:30 p.m. ET. The event will include a brief presentation on navigating opportunities and challenges APPs face in clinical practice, led by Danielle McCamey, DNP, CRNP, ACNP-BC, FCCP; and Corinne Young, MSN, FNP-C, FCCP. Presenters will give practical tips for making the most of the CHEST 2024 experience. The forum will be held in the Contemporary Ballroom at the Omni Hotel. The Women in Chest Medicine Annual Luncheon , Monday, October 7, 12:00 to 1:30 p.m. ET. National negotiation expert and best-selling author, Sara Laschever, will facilitate an interactive conversation about cultivating effective negotiation skills and how to be your best self-advocate. In addition, the 2024 recipient of the CHEST Women’s Lung Health grant will be honored at the luncheon. The luncheon will be held in room 156A at the Boston Convention and Exhibition Center. Tyvaso DPI® (Treprostinil Inhalation Powder): Clinical Pearls and Drug-Device Characteristics , Monday, October 7, 6:00 to 9:00 p.m. ET, featuring Anthony Hickey, Ph.D., Sc.D., University of North Carolina at Chapel Hill; Jennifer H Keeley, DNP, Allegheny General Hospital; and Sandeep Sahay, M.D., FCCP, Houston Methodist Hospital. The symposium will be held at the Omni Boston Hotel at the Seaport, Momentum ABC Ballroom, Level 5. About Tyvaso® Inhalation Solution and Tyvaso DPI® Inhalation Powder INDICATION TYVASO (treprostinil) Inhalation Solution and TYVASO DPI (treprostinil) Inhalation Powder are prostacyclin mimetics indicated for the treatment of: Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration. Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS TYVASO and TYVASO DPI are pulmonary and systemic vasodilators. In patients with low systemic arterial pressure, either product may produce symptomatic hypotension. Both products inhibit platelet aggregation and increase the risk of bleeding. Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both C max and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness. Like other inhaled prostaglandins, TYVASO and TYVASO DPI may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO and TYVASO DPI. DRUG INTERACTIONS/SPECIFIC POPULATIONS The concomitant use of either product with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both C max and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8. Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production. Safety and effectiveness in pediatric patients have not been established. Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH‑ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy. ADVERSE REACTIONS Pulmonary Arterial Hypertension (WHO Group 1) In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea. In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of TYVASO who switched to a corresponding dose of TYVASO DPI, the most commonly reported adverse events seen with TYVASO DPI in ≥4% of PAH patients during the 3-week treatment phase included cough (35.3%), headache (15.7%), dyspnea (7.8%), and nausea (5.9%). Pulmonary Hypertension Associated with ILD (WHO Group 3) In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH. Please see Full Prescribing Information for TYVASO or TYVASO DPI , Instructions for Use manuals for TD-100 and TD-300 TYVASO ® Inhalation System and TYVASO DPI ™ Inhalation Powder , and additional information at www.TYVASOHCP.com or call 1‑877‑UNITHER (1-877-864-8437). TYVISIhcpMAY2022revised United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun, we do good. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation ( PBC ). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs. You can learn more about what it means to be a PBC here: unither.com/pbc . Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders, furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of September 24, 2024, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. TYVASO and TYVASO DPI are registered trademarks of United Therapeutics Corporation.