Amyloidosis

Alnylam CEO Yvonne Greenstreet, M.D., characterizes Amvuttra's entrance in the suddenly competitive ATTR-CM market as a "category growth story." With attention focused on their recently approved drugs for transthyretin amyloid cardiomyopathy (ATTR-CM), there was a serendipitous timeliness to Alnylam and BridgeBio presenting their quarterly updates on consecutive days.While BridgeBio blew away analyst projections on Wednesday, reporting sales of $37 million for Attruby in its first full quarter on the market, Alnylam countered with positive news as well for Amvuttra on Thursday.Since Amvuttra earned its FDA label expansion to treat patients with ATTR-CM so late in the first quarter on March 20, there were no significant sales to report for the indication. But the company is pointing to encouraging signs in its uptake.“Our first priority out of the gate was the access setup and we’re pleased to say it’s progressing exactly to plan, enabling the second half growth story that we have portrayed,” Tolga Tanguler, Alnylam’s chief commercial officer, said during a conference call.Tanguler explained that 80% of TTR volume in the U.S. flows through 170 health systems, and that the company had gained formulary placements of Amvutta within four weeks of the label expansion at more than half of the systems. He added that a “majority” have initiated Amvuttra treatment for ATTR-CM patients.Tanguler also reported early feedback from patients and doctors indicates “excitement for a new mechanism of action in ATTR-CM.”“What we’re hearing from prescribers is that the Amvuttra’s disruptive value proposition resonates and is enabling this early encouraging launch momentum,” Tangular said.Alnylam and BridgeBio are challenging powerhouse Pfizer, which has dominated the market with its booming Vyndaqel franchise. In 2024, the Pfizer treatments achieved sales of $5.4 billion, which was up from $3.3 billion in 2023.Alnylam CEO Yvonne Greenstreet, M.D., said there is plenty of room for new options for ATTR-CM patients.“We really are in a category growth story,” Greenstreet said. “What we’re seeing is continued evidence of a large, growing, and frankly, unsatisfied market and I think we’re very excited to be able to participate.” Alnylam points to its experience with treating patients with polyneuropathy caused by hereditary transthyretin amyloidosis (hATTR-PN). The company earned approvals for Onpattro (2018) and Amvuttra (2022) to treat the condition.“We are finding that in categories where the majority of patients remain untreated, more treatment options mean more voices helping to raise disease awareness ultimately accelerating category growth and increasing the number of patients on therapy,” Tanguler said. “We believe about 80% of the addressable patient population remains untreated. This bodes well for the opportunity ahead in ATTR-CM.” In the first quarter, sales for Amvuttra and Onpattro came in at $310 million and $49 million, which were up a combined 37% year over year and 4% sequentially. The combined $359 million TTR franchise sales were in line with the analysts' forecast of $355 million.In 2024, sales of the two treatments were at $1.22 billion. With the new indication for Amvuttra, the company is sticking to its previously announced guidance for the pair to generate between $1.6 billion and $1.725 billion in 2025.For the company overall, revenue was up in the quarter 20% to $594 million. Alnylam is guiding to overall sales of between $2.05 billion and $2.25 billion, which would be a 31% increase year over year at midpoint.

DUBLIN--(BUSINESS WIRE)-- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today announced that it will report its first quarter 2025 financial results on Thursday, May 8, 2025, after the close of the U.S. financial markets. Consistent with past practice, the Company will not be conducting a conference call in conjunction with the financial results release on May 8. About Prothena Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena’s pipeline includes both wholly-owned and partnered programs being developed for the potential treatment of diseases including AL amyloidosis, ATTR amyloidosis with cardiomyopathy, Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. For more information, please visit the Company’s website at www.prothena.com and follow the Company on X (formerly Twitter) @ProthenaCorp. Investors Mark Johnson, CFA, Vice President, Investor Relations 650-417-1974, mark.johnson@prothena.com Media Michael Bachner, Senior Director, Corporate Communications 609-664-7308, michael.bachner@prothena.com

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.