Pioglitazone Hydrochloride

Achieved global net product revenues for AMVUTTRA and ONPATTRO for the first quarter of $310 million and $49 million , respectively, representing 36% growth compared to Q1 2024. Achieved global net product revenues for GIVLAARI and OXLUMO for the first quarter of $67 million and $42 million , respectively, representing 8% growth compared to Q1 2024. Strong progress making AMVUTTRA available for ATTR-CM in various global markets. Received U.S. FDA approval of the supplemental New Drug Application (sNDA) for AMVUTTRA for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. Received approval from ANVISA ( Brazilian Health Regulatory Agency ) for ATTR-CM. Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of vutrisiran for the treatment of ATTR-CM. Marketing authorization applications based on data from the landmark HELIOS-B Phase 3 clinical trial are currently under review by several global health agencies including the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Presented new data from HELIOS-B at the American College of Cardiology Scientific Session 2025, further supporting vutrisiran’s compelling therapeutic profile, including: Echocardiographic data demonstrating that treatment with vutrisiran led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. HELIOS-B included the largest systematic echocardiographic study conducted to date in an ATTR pivotal trial. An exploratory subgroup analysis demonstrating that vutrisiran reduced all-cause mortality and recurrent cardiovascular events compared to placebo across a range of baseline heart failure severities in patients with ATTR-CM. These data were also published in the Journal of the American College of Cardiology . A separate analysis confirming that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. These data were also published in the Journal of the American College of Cardiology . Presented updates from the Company’s robust pipeline and organic platform at R&D Day. Disclosed two new clinical programs: ALN-6400, targeting liver-derived plasminogen, which could represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. ALN-4324, targeting GRB14, a potential insulin sensitizer for the treatment of type 2 diabetes. Alnylam announces today that a Phase 1 clinical trial for ALN-4324 has been initiated. Shared encouraging data from our expanding neuroscience franchise, including an update on the new ALN-HTT02 program, which has a highly differentiated exon-1-targeting approach to lower huntingtin (HTT) for Huntington’s disease. Presented new preclinical data on delivery solutions with best-in-class potential for adipose, muscle, heart, and kidney tissue and for crossing the blood-brain barrier, supporting Alnylam’s aspiration to unlock every major tissue for RNAi therapeutics by 2030. Received U.S. FDA approval of the supplemental New Drug Application (sNDA) for AMVUTTRA for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. Received approval from ANVISA ( Brazilian Health Regulatory Agency ) for ATTR-CM. Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of vutrisiran for the treatment of ATTR-CM. Marketing authorization applications based on data from the landmark HELIOS-B Phase 3 clinical trial are currently under review by several global health agencies including the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Echocardiographic data demonstrating that treatment with vutrisiran led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. HELIOS-B included the largest systematic echocardiographic study conducted to date in an ATTR pivotal trial. An exploratory subgroup analysis demonstrating that vutrisiran reduced all-cause mortality and recurrent cardiovascular events compared to placebo across a range of baseline heart failure severities in patients with ATTR-CM. These data were also published in the Journal of the American College of Cardiology . A separate analysis confirming that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. These data were also published in the Journal of the American College of Cardiology . Disclosed two new clinical programs: ALN-6400, targeting liver-derived plasminogen, which could represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. ALN-4324, targeting GRB14, a potential insulin sensitizer for the treatment of type 2 diabetes. Alnylam announces today that a Phase 1 clinical trial for ALN-4324 has been initiated. Shared encouraging data from our expanding neuroscience franchise, including an update on the new ALN-HTT02 program, which has a highly differentiated exon-1-targeting approach to lower huntingtin (HTT) for Huntington’s disease. Presented new preclinical data on delivery solutions with best-in-class potential for adipose, muscle, heart, and kidney tissue and for crossing the blood-brain barrier, supporting Alnylam’s aspiration to unlock every major tissue for RNAi therapeutics by 2030. ALN-6400, targeting liver-derived plasminogen, which could represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. ALN-4324, targeting GRB14, a potential insulin sensitizer for the treatment of type 2 diabetes. Alnylam announces today that a Phase 1 clinical trial for ALN-4324 has been initiated. Net product revenues increased 28% and 30% at actual currency and CER, respectively, during the three months ended March 31, 2025 , as compared to the same period in 2024, due to growth from AMVUTTRA driven by increased patient demand, partially offset by a decrease in ONPATTRO due to patient switches to AMVUTTRA, as well as an increased number patients on GIVLAARI. Net revenues from collaborations decreased during the three months ended March 31, 2025 , as compared to the same period in 2024, primarily due to recognition of $65.0 million of revenue associated with a milestone under our Roche Collaboration from dosing the first patient in the zilebesiran KARDIA-3 clinical trial during the three months ended March 31, 2024 , which did not reoccur during the three months ended March 31, 2025 . This was partially offset by increased revenue recognized in connection with our Regeneron Collaboration during the three months ended March 31, 2025 as a result of an increase in activities under our licensed programs and recognition of a $30.0 million payment in connection with the amendment to our agreement with Vir Biotechnology, Inc. in March 2025 . Cost of goods sold as a percentage of net product revenues was consistent during the three months ended March 31, 2025 , as compared to the same period in 2024. GAAP R&D expenses increased during the three months ended March 31, 2025 , as compared to the same period in 2024, primarily due to: increased stock-based compensation expense; and increased clinical trial expenses primarily associated with zilebesiran in the KARDIA-3 clinical trial and mivelsiran in the cAPPRicorn-1 clinical trial due to increased Phase 2 activities, as well as startup activities and other clinical trial expenses associated with zilebesiran in the KARDIA-6 cardiovascular outcomes trial and nucresiran in the TRITON-CM Phase 3 clinical trial in patients with ATTR amyloidosis with cardiomyopathy. increased stock-based compensation expense; and increased clinical trial expenses primarily associated with zilebesiran in the KARDIA-3 clinical trial and mivelsiran in the cAPPRicorn-1 clinical trial due to increased Phase 2 activities, as well as startup activities and other clinical trial expenses associated with zilebesiran in the KARDIA-6 cardiovascular outcomes trial and nucresiran in the TRITON-CM Phase 3 clinical trial in patients with ATTR amyloidosis with cardiomyopathy. decreased expenses within other clinical programs, specifically the HELIOS-B Phase 3 clinical trial of vutrisiran due to the wind-down of clinical activities. GAAP and non-GAAP SG&A expenses increased during the three months ended March 31, 2025 , as compared to the same period in 2024, primarily due to increased marketing investment associated with the promotion of our TTR therapies and increased employee compensation expenses. Interest expense for the three months ended March 31, 2025 of $38.6 million included interest of $35.0 million attributed to the liability related to the sale of future Leqvio royalties. Other expense, net for the three months ended March 31, 2025 of $59.7 million included a charge associated with the change in fair value of the development derivative liability of $58.9 million , attributed to valuation updates primarily driven by the regulatory approval of AMVUTTRA for the treatment ATTR-CM. During the three months ended March 31, 2025 , we recorded a provision for income taxes of $15.9 million , primarily due to income generated in Switzerland . We will utilize deferred tax assets in Switzerland to offset current cash tax liabilities and will continue to maintain a full valuation allowance against our net deferred tax assets in the U.S. and certain deferred tax assets in Switzerland . Cash, cash equivalents and marketable securities were $2.63 billion as of March 31, 2025 , as compared to $2.69 billion as of December 31, 2024 , with the decrease primarily driven by operating activities. Net cash used in operating activities for the three months ended March 31, 2025 of $118.3 million , included $61.7 million of payments associated with the liability related to the sale of future Leqvio royalties allocated to interest. Net cash provided by financing activities for the three months ended March 31, 2025 of $44.1 million , included $5.3 million of payments associated with an achieved development milestone for the development derivative liability.

The annual meeting of the American Academy of Dermatology was held from March 7 to 11 in Orlando, Florida, and attracted clinicians, academicians, allied health professionals, and others interested in dermatology. The conference highlighted recent advances in the diagnosis and management of dermatological conditions. During one presentation, Joshua Cook, M.D., of the Columbia University Irving Medical Center in New York City, noted that targeting insulin resistance and hyperinsulinemia is important not only for the treatment of obesity and diabetes, but potentially also independently for improving metabolism-related inflammatory skin diseases like psoriasis and hidradenitis suppurativa. Cook discussed the tight epidemiologic connection between obesity, type 2 diabetes, and inflammatory skin diseases, especially psoriasis. The mechanistic basis of this connection is likely due to insulin resistance and/or hyperinsulinemia. Cook noted that hyperinsulinemia likely drives excessive proliferation and inflammation of skin lesions in psoriasis and other inflammatory skin diseases, even in the setting of systemic insulin resistance. "We are currently performing clinical studies to better understand the role of insulin action in psoriasis," Cook said. "Health care providers should strongly consider screening patients with overweight/obesity and inflammatory skin diseases with hemoglobin A1c, fasting glucose, and lipid profiles. Treatment of obesity and type 2 diabetes with glucagon-like peptide-1 receptor agonists may improve inflammatory skin disease activity (an area of active research). There may also be roles for metformin and pioglitazone in inflammatory skin disease treatment in select patients." Abstract During another presentation, Daniel Charles Butler, M.D., of the University of Arizona College of Medicine in Tucson, discussed the connection between itch and aging. Butler discussed how itch is very common in the older adult population. He noted there are many etiologic contributors to itch, including the immune system, the skin barrier, and the cutaneous nerves, all of which are uniquely impacted by aging. "As practicing clinicians, we need to substantiate itch as a real, impactful but targetable symptom and disease," Butler said. "The connection between age and itching allows us to target contributing etiologies with available treatments. For example, itch in older adults is often multifactorial with immunologic changes and neuropathic changes. This allows us to use treatment to target multiple contributors." Butler disclosed financial ties to the pharmaceutical industry. Abstract Adam J. Friedman, M.D., of the George Washington School of Medicine and Health Sciences in Washington, D.C., discussed how food allergy is an extremely rare cause of chronic urticaria with no identifiable cause (CSU), and some food intolerances may contribute, but responses are highly individualized and elimination diets should only be done in a structured way. Friedman provided insight into how urticaria, both acute and chronic, is a common condition, affecting as many as 80 percent of people at some point in their lives. For approximately 1 percent of individuals who develop chronic urticaria, this condition can last for years, significantly impacting quality of life. While patients often search for a clear trigger, more than two-thirds of cases occur without an identifiable cause. Although food allergies can trigger acute urticaria, particularly in children, when it comes to CSU, food allergy is rarely a culprit. Friedman noted that, instead, he often sees food intolerances or pseudoallergic reactions, which may contribute to symptoms in some individuals. This distinction is important because a true food allergy involves an immune response, and food intolerances tend to be more variable, harder to predict, and less understood. A number of studies have explored dietary interventions in CSU, but the results so far have been mixed at best. "At the end of the day, lifestyle modifications are cost-effective, noninvasive, and worth exploring, but they require proper education and guidance -- both for patients and physicians. This remains an underfunded and underresearched area, but as interest grows, we may gain clearer insights into how diet influences CSU," Friedman said. "While it's tempting to believe that cutting out a few foods might be a silver bullet, CSU is a complex, multifactorial condition. And as with most things in dermatology, there's rarely a one-size-fits-all approach." Friedman disclosed financial ties to the pharmaceutical industry. Abstract Peggy A. Wu, M.D., of the University of California Davis in Sacramento, discussed how systemic contact dermatitis (SCD) is a diagnosis to consider in the setting of a chronic, recalcitrant rash in the right clinical setting, although the diagnosis is not common. Wu discussed how SCD represents a small subset of allergic contact dermatitis (ACD) diagnoses. Like ACD, SCD is thought to be a delayed hypersensitivity reaction, and as such, reactions follow exposures in hours to days. SCD can present in a myriad of ways, including, most commonly, vesicular bilateral hand dermatitis, generalized dermatitis, and periorificial dermatitis. Frequent causes of SCD include exposure to nickel, balsam of Peru, and fragrance. The diagnosis is usually made in the setting of a chronic rash with positive patch test results to an allergen with plausible, relevant dietary sources and following topical avoidance of identified allergens. "Physicians should consider the diagnosis of SCD in the setting of a recalcitrant chronic rash with certain phenotypes (vesicular bilateral hand dermatitis, generalized dermatitis, periorificial) and positive patch test reactions to allergen(s) with a possible relevant dietary source," Wu said. "A recommended approach to SCD is to start with a one-month trial of dietary modification. Longer courses of dietary modification may benefit from working with a dietitian to maintain nutritional need." Abstract AAD: Baricitinib Efficacious for Hair Regrowth in Teens With Severe Alopecia Areata TUESDAY, March 18, 2025 -- For adolescents with severe alopecia areata, baricitinib is efficacious for hair regrowth, according to a study presented at the annual meeting of the American Academy of Dermatology, held from March 7 to 11 in Orlando, Florida. Read Full Text AAD: Maintenance of Low Eczema Activity Seen After About 80 Days Off Tapinarof FRIDAY, March 14, 2025 -- Patients with atopic dermatitis who achieve completely clear skin with tapinarof ( Vtama ) cream maintain low disease activity after about 80 days off treatment, according to a study presented at the annual meeting of the American Academy of Dermatology, held from March 7 to 11 in Orlando, Florida. Read Full Text AAD: Ivarmacitinib 4 mg, 8 mg Efficacious for Adults With Severe Alopecia Areata THURSDAY, March 13, 2025 -- For adults with severe alopecia areata, ivarmacitinib, a selective Janus kinase 1 inhibitor, at doses of 4 and 8 mg is efficacious and tolerable, according to a study presented at the annual meeting of the American Academy of Dermatology, held from March 7 to 11 in Orlando, Florida. Read Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.