Carotid Stenosis

THURSDAY, March 20, 2025 -- For patients undergoing carotid endarterectomy, sonolysis is safe and results in a significant reduction in the composite incidence of ischemic stroke , transient ischemic attack , and death within 30 days, according to a study published online March 19 in The BMJ . David Školoudík, Ph.D., from the University of Ostrava in the Czech Republic, and colleagues examined the effectiveness and safety of sonolysis using a low-intensity 2-MHz pulsed wave ultrasound beam during carotid endarterectomy in a phase 3 trial involving 1,004 patients from 16 European centers. Participants were randomly assigned to receive sonolysis or sham procedure (507 and 497 individuals, respectively). The composite incidence of ischemic stroke, transient ischemic attack, and death within 30 days was the primary end point. The researchers found that the results favored sonolysis for the primary end point (2.2 versus 7.6 percent) and in the substudy for magnetic resonance imaging-detected new ischemic lesions (8.5 versus 17.4 percent). In a sensitivity analysis, the risk ratios for sonolysis were 0.25 and 0.23 for ischemic stroke and transient ischemic stroke, respectively, within 30 days. Sonolysis was safe; 30 days after the procedure, 94.4 percent of patients were free from serious adverse events. "Sonolysis should be used to reduce the risk of periprocedural cerebrovascular events during carotid endarterectomy in all patients with sufficient temporal bone window for transcranial Doppler," the authors write. "It has the potential to make carotid endarterectomy safer with a higher benefit for patients with carotid stenosis compared with the best medical treatment, especially in patients with asymptomatic carotid stenosis." Abstract/Full Text Editorial (subscription or payment may be required) Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

LAS VEGAS, Nov. 4, 2024 /PRNewswire/ -- The VIVA Foundation, a not-for-profit organization dedicated to advancing the field of vascular medicine and intervention through education and research, announces the results for the first two rounds of Late-Breaking Clinical Trials presented at the VIVA24 conference, at Wynn Las Vegas. VIVA (Vascular InterVentional Advances) is an annual vascular education symposium that brings together a global, multispecialty faculty to present a variety of lectures and live case presentations from clinical centers around the world. The audience is comprised of interventional cardiologists, interventional radiologists, vascular surgeons, and endovascular medicine specialists. Below are highlights of today's 9 late-breaking clinical trial presentations. Two-Year Outcomes of the LIFE-BTK Randomized Controlled Trial Evaluating the Esprit™ BTK Drug-Eluting Resorbable Scaffold for Treatment of Infrapopliteal Lesions Presented by: Brian DeRubertis, MD The 2-year results from the LIFE-BTK randomized controlled trial highlight the sustained benefits of the Esprit Below-the-Knee (BTK) Drug-Eluting Resorbable Scaffold (Abbott) in treating patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal lesions. Esprit BTK demonstrated superior long-term outcomes compared to percutaneous transluminal angioplasty (PTA), particularly in terms of vessel patency and limb salvage. At 2 years, 61.5% of patients treated with Esprit BTK achieved the combined endpoint of limb salvage and primary patency, compared to 32.8% in the PTA group. This marked an absolute risk difference (ARD) of 28.66% and a hazard ratio of 0.48 (P = .0004), confirming the scaffold's superior efficacy in maintaining open arteries and preventing disease progression. The scaffold's biological efficacy was evident in its ability to significantly reduce binary restenosis, with rates of 35.2% for Esprit BTK compared to 57.8% for PTA (ARD, -22.57%; P = .0054), ensuring continued vessel patency over time. The composite of freedom from major adverse limb events at 2 years and perioperative death at 30 days was comparable between the two arms, with Esprit BTK achieving a 90.4% safety rate versus a 95.9% safety rate with PTA (P = .16), demonstrating that the scaffold offers a safe alternative for infrapopliteal interventions. The 2-year outcomes of the LIFE-BTK trial suggest durable performance and long-term benefits with Esprit BTK. Its ability to maintain vessel patency and reduce restenosis presents a promising treatment option for CLTI patients, with efficacy and safety outcomes that compare favorably to PTA. First Clinical Use of an Innovative Forward-Shifted Peripheral Intravascular Lithotripsy System: Late-Breaking Primary Outcomes of the Mini S/FORWARD PAD IDE Study Presented by: JD Corl, MD Successful endovascular treatment of peripheral artery disease is dependent on the modification of challenging lesion morphologies. The Shockwave Javelin Peripheral Intravascular Lithotripsy (IVL) catheter (Shockwave Medical) has a forward-shifted IVL emitter designed to modify calcium in subtotal occlusions or extremely narrowed calcified vessels. The premarket, prospective, single-arm Mini S feasibility and FORWARD PAD IDE studies were pooled, and this analysis includes 103 lesions in 90 patients treated at 19 sites in Australia, New Zealand, and the United States. The primary effectiveness endpoint was defined as residual stenosis ≤ 50% without flow-limiting dissection at final angiography, and the primary safety endpoint was major adverse events at 30 days. Endpoints were adjudicated by an angiographic core laboratory and a clinical events committee. Lesion characteristics included preprocedural stenosis of 82.9% ± 16.7%, severe calcification present in 82.5%, and 38% chronic total occlusions. The Javelin catheter was able to fully cross the target lesion in 93% of cases. The primary effectiveness (99%; P < .0001) and primary safety endpoints (1.1%; P = .0012) both met prespecified performance goals. Baseline stenosis was reduced to 23% ± 9.1% at final angiography, and there were no perforations or embolization events through 30 days. In this 30-day analysis, the Shockwave Javelin Peripheral IVL catheter met prespecified efficacy and safety performance goals, with marked target lesion stenosis reduction without perforations or distal embolization. Further follow-up will assess longer-term outcomes with the Javelin Peripheral IVL catheter. Thirty-Day Outcomes From the Disrupt PAD BTK II Study of the Shockwave Intravascular Lithotripsy System for Treatment of Calcified Below-the-Knee PAD Presented by: Venita Chandra, MD Below-the-knee (BTK) lesions may be particularly challenging to treat owing to length, diffuse disease, and extent of calcification. The Disrupt PAD BTK II study is a core lab–adjudicated, prospective, multicenter, single-arm study of patients with moderately to severely calcified BTK lesions treated with the Shockwave Peripheral Intravascular Lithotripsy (IVL) System (Shockwave Medical). Disrupt PAD BTK II enrolled 250 patients with calcified infrapopliteal lesions and Rutherford category 3 to 5 presentation from 38 sites in the United States and Europe. The primary safety endpoint was major adverse limb events (MALE) or postoperative death at 30 days. The primary effectiveness endpoint was procedural success, defined as ≤ 50% residual stenosis for all treated target lesions without serious core lab–adjudicated serious angiographic complications. Follow-up is planned through 2 years. A total of 305 lesions in 250 patients were treated with a procedural success of 97.9%. Mean target lesion length was 76.3 ± 65.2 mm, diameter stenosis was 77.7% ± 17.9%, and 84.8% had moderate or severe calcification as assessed by an independent angiographic core lab. After IVL, residual stenosis was reduced to 29% and to 25.5% after optional postdilatation and/or stent implantation. At 30 days, there were no deaths, the MALE rate was 0.8%, and mean improvement in VascuQoL scores was 4 ± 5 (P < .0001). Of the patients with baseline wounds, 15.8% healed and 53.4% were improved at 30 days. IVL treatment of patients with moderately to severely calcified BTK lesions resulted in high procedural success, significant reduction in residual stenosis, and improvements in patient quality of life and wound healing, with minimal adverse events at 30-day follow-up. These outcomes support the safety and effectiveness of IVL in the treatment of patients with complex calcified BTK lesions. Laser and Optics-Based Peripheral Intravascular Lithotripsy System for the Treatment of Above-the-Knee and Below-the-Knee Calcified Lesions: Results of the RESTORE ATK and RESTORE BTK Trials Presented by: Thomas Zeller, MD Arterial calcification portends poor procedural success for peripheral vascular interventions and suboptimal long-term outcomes. These studies aimed to evaluate the initial safety and efficacy of a novel laser and optics-based intravascular lithotripsy (IVL) system for calcified lesions in the peripheral vasculature (Bolt IVL, Bolt Medical). The RESTORE ATK and RESTORE BTK trials were prospective, nonrandomized, multicenter studies conducted in Europe. Patients were treated with IVL and followed to 6 months (above the knee [ATK]) and 30 days (below the knee [BTK]). The primary safety endpoints were freedom from major adverse events (MAEs) (composite of death, clinically driven target limb revascularization [CD-TLR], and unplanned major amputation) within 30 days following the index procedure. Efficacy endpoints included procedural success (residual diameter stenosis < 50%) evaluated by an independent core laboratory. Ninety-five (ATK) and 20 (BTK) patients were enrolled. The mean age for ATK and BTK was 70 ± 8 years and 73 ± 10 years, with 33% and 30% females, respectively. The superficial femoral and anterior tibial arteries were the most treated in each trial, with a mean vessel diameter of 5.5 ± 0.7 mm and 2.9 ± 0.4 mm, respectively, and percent diameter stenosis of 93.7% ± 7.2% and 91.4% ± 8.8%, respectively. The efficacy endpoint was achieved in 100% of patients in both studies. Residual diameter stenosis postprocedure was 21.2% ± 8.4% (ATK) and 22.8% ± 11.5% (BTK) with no MAEs occurring within 30 days. No cases of perforation, abrupt closure, no reflow, distal embolization, or dissections meeting serious AE criteria were observed. No stents were placed in BTK, and only three were placed in ATK despite the lesion complexity, length, and chronic total occlusions. Ninety-two ATK patients completed 6-month follow-up, and 18 BTK patients completed 30-day follow-up, with 2.2% and 0% CD-TLR, respectively, and no deaths or limb amputations. These studies demonstrate the safety and effectiveness of a novel laser and optics-based IVL catheter for treatment of severely calcified ATK and BTK peripheral lesions. Total REALITY: Comparison of Directional Atherectomy vs Balloon Predilatation Prior to Drug-Coated Balloon Treatment of Long, Calcified Femoropopliteal Lesions Presented by: Venita Chandra, MD Drug-coated devices provide good long-term outcomes for femoropopliteal revascularization, but calcification can limit drug uptake. Vessel preparation with atherectomy may provide better periprocedural results than standard predilatation, reducing the need for permanent scaffolds and preserving future treatment options. However, there are limited randomized trial data supporting its use. The single-arm, prospective, multicenter VIVA REALITY study evaluated directional atherectomy (DA) prior to use of drug-coated balloons (DCBs) in highly calcified lesions. In an updated analysis, investigators used pooled data from the REALITY study and data from prospective, multicenter studies evaluating DCB with standard predilatation to determine whether DA prior to DCB would result in less provisional stent use and comparable safety and effectiveness versus percutaneous transluminal angioplasty (PTA) followed by DCB. In the Total REALITY analysis, patients in the REALITY study treated with DA plus DCB (n = 84) were matched by propensity scores to eligible patients treated with PTA plus DCB from the Total IN.PACT data set (n = 143). All studies included angiographic and duplex ultrasound (DUS) core laboratories and event adjudication by independent clinical event committees. Significant differences in severe calcification (PACSS 4) persisted after matching (71.4% for DA + DCB vs 5.9% for PTA + DCB; P < .001). As expected, 12-month primary patency (freedom from both clinically driven target lesion revascularization and DUS-derived restenosis) did not differ between groups. In the DA plus DCB arm, there was a trend toward higher stent-free patency through 12 months using Kaplan-Meier estimates (79.1% vs 68.1%; P = .09) and a significantly lower provisional stent rate (9.5% vs 21.1%; P = .014). Major adverse limb events did not differ between groups. The Total REALITY analysis underscores the complexity of lesions included in the REALITY study, particularly the high prevalence of severe calcification. Nevertheless, DA plus DCB achieved a significantly lower provisional stent rate and trended toward higher stent-free patency. DA plus DCB is a viable, safe, and effective alternative to PTA plus DCB in treating long and highly calcified lesions while reducing the need for permanent implants. Prospective, Multicenter Evaluation of Transcarotid Artery Revascularization in Standard-Risk Patients: 30-Day Outcomes of the ROADSTER 3 Study Presented by: Meghan Dermody, MD The ROADSTER 3 study is the first-ever prospective, multicenter trial evaluating the safety and effectiveness of transcarotid artery revascularization (TCAR) using the ENROUTE Transcarotid Stent System (TSS) in conjunction with the ENROUTE Transcarotid Neuroprotection System (NPS) (both Boston Scientific Corporation) for the treatment of carotid stenosis in standard-surgical-risk patients. The primary endpoint for this single-arm, postapproval study is a composite of major adverse events (stroke, death, or myocardial infarction [MI]) through 30 days postprocedure, plus ipsilateral stroke from day 31 to 365 postprocedure. The incidence of cranial nerve injury (CNI) within 30 days postprocedure is a key secondary endpoint. All patients underwent independent neurologic assessments before the procedure, as well as within 24 hours, at 30 days, and at 1 year after TCAR. Events were adjudicated by an independent clinical events committee. Of the 344 patients enrolled (320 treated per-protocol [PP]) at 53 United States sites, 75.3% were aged < 75 years, 42.7% were female, and 16.3% were symptomatic. Among symptomatic patients, 25% experienced a neurologic event within 2 weeks preceding TCAR. The mean lesion length was 23.3 mm, 47.4% had a type II or type III aortic arch, and 17.2% of lesions had severe calcification. In the intent-to-treat population, the rate of stroke/death/MI at 30 days was 0.9% (0.6% PP) with a 30-day stroke rate of 0.9% (0.6% PP). There were no deaths or MIs through 30-day follow-up. The incidence of CNI within 30 days was 0.6% (0.6% PP); both resolved within 6 months. These 30-day results of the ROADSTER 3 study demonstrate that TCAR, using the ENROUTE TSS in conjunction with the ENROUTE NPS, is safe and effective in patients at standard risk for adverse events from carotid endarterectomy. Two-Year Outcomes of the PERFORMANCE II Trial: A Prospective, Multicenter, Single-Arm Investigation of a 3-in-1 Carotid Stent System With Integrated Embolic Protection Presented by: William A. Gray, MD The PERFORMANCE II study is a prospective, multicenter, single-arm, open-label study evaluating the safety and effectiveness of the Neuroguard IEP 3-in-1 Carotid Stent System (Contego Medical) with integrated embolic protection (IEP) for the treatment of carotid artery stenosis in patients at elevated risk for adverse events following carotid endarterectomy. 305 patients were enrolled at 32 sites in the United States and Europe. The primary endpoint was the 30-day rate of major adverse events (MAEs), defined as death, all stroke, and myocardial infarction (MI) within 30 days of the index procedure, plus ipsilateral stroke through 12 months of the procedure. Events were adjudicated by an independent clinical events committee. Imaging was analyzed by an independent core lab. Twenty percent of patients were symptomatic, and 43.5% were diabetic. 230 (75%) patients presented with physiologic high-risk criteria, 75 (25%) patients had anatomic high-risk criteria, and 85 (28%) had both. The mean target lesion stenosis was 85%, and 34% were severely calcified. In a per-protocol analysis, the 30-day stroke rate was 1% (3 patients). In an intention-to-treat analysis, the 30-day stroke rate was 1.3% (4 patients), the death/stroke rate was 1.6% (5 patients), and the death/stroke/MI rate was 2.3% (7 patients). The rate of 30-day all-stroke plus ipsilateral stroke through 1 year was 1.8% (5 patients), all of which were minor. There were no major strokes, stent thrombosis, or neurologic deaths through 2 years. The rate of in-stent restenosis (ISR) was 3.65% at 1 year and 3.85% at 2 years. There was no clinically driven target lesion revascularization (CD-TLR) at 1 year and one CD-TLR (0.36%) at 2 years. These 2-year results of the PERFORMANCE II study demonstrate the remarkable procedural safety and long-term durability of the Neuroguard IEP 3-in-1 Carotid Stent System in high-surgical-risk patients. Despite a 43.5% rate of diabetes and 34% rate of severe calcification, the 3.85% rate of ISR and 0.36% rate of CD-TLR at 2 years were very low. Healthcare Resource Utilization and Outcomes Among Patients With Intermediate-Risk PE Treated With Computer-Assisted Vacuum Thrombectomy vs Other Treatment Modalities Presented by: Parag J. Patel, MD, MS This nationwide retrospective study evaluates health care resource utilization and outcomes among patients with intermediate-risk pulmonary embolism (PE) treated with computer-assisted vacuum thrombectomy (CAVT) (Penumbra, Inc.) compared to anticoagulation (AC), catheter-directed thrombolysis (CDL), or other mechanical thrombectomy (MT) in the United States. Using data from the Vizient clinical database, adult inpatients with intermediate-risk PE discharged between July 1, 2020, and September 30, 2023, were identified. ICD-10 procedure codes were used to identify treatment modalities. A total of 2,060 patients were propensity matched 1:1 to equate 515 CAVT patients to AC, CDL, and MT patients using demographics, Elixhauser Comorbidity Index, payer, and hospital type. Key results showed that CAVT patients experienced significantly shorter length of stay (LOS) (4.6 ± 3.2 days) compared to AC (6.2 ± 3.7 days), CDL (7.1 ± 4.4 days), and MT (7 ± 4.6 days) patients (P < .0001). Additionally, postprocedure LOS was shorter for CAVT patients (3.8 ± 3.2 days) than CDL (6.1 ± 4.3 days; P < .0001) or MT (6.2 ± 4.5 days; P < .0001) patients. Postprocedure intensive care unit (ICU) utilization was lower in the CAVT group compared to the CDL group (44.3% vs 82.7%; P < .0001), with a shorter mean ICU stay (0.7 ± 1.3 days vs 1.6 ± 1.5 days; P < .0001). CAVT patients had fewer composite complications versus MT patients (1.2% vs 4.1%; P = .0034) and had a reduced incidence of acute kidney injury developing during the hospitalization compared to the MT (1.9% vs 4.9%; P = .0099) and CDL groups (1.9% vs 4.5%; P = .0214). No differences were observed between CAVT and the other groups for in-hospital mortality, 30-day all-cause mortality, and PE-related readmissions. CAVT for the treatment of intermediate-risk PE led to significant reduction of hospital LOS and fewer complications without increasing mortality or readmissions compared to AC, CDL, and other MT. Complete Two-Year Outcomes in Patients Receiving Mechanical Thrombectomy for DVT in the CLOUT Registry Presented by: David J. Dexter, MD Prospective data detailing long-term outcomes following endovascular treatment for deep vein thrombosis (DVT) are limited due to the field's relatively recent development. The CLOUT registry is a prospective, multicenter study evaluating patient outcomes following mechanical thrombectomy (MT) with the ClotTriever System (Inari Medical) in proximal lower extremity DVT. This presentation represents the largest available data set detailing MT outcomes for DVT and the first reporting of final results through 2 years from all available patients enrolled in the completed CLOUT registry. Study inclusion was all-comer: patients were aged ≥ 18 years and enrolled regardless of bilateral disease, duration of symptoms, prior treatment for the current DVT, or contraindications to thrombolytic therapy. In total, 285 patients completed the 2-year follow-up visit. At 2 years post-MT, 81.5% of treated limbs had no postthrombotic syndrome (PTS; Villalta score < 5) compared to 18.8% at baseline. Furthermore, the prevalence of moderate or severe PTS (Villalta score ≥ 10) was 6.4% at 2 years compared to 46.9% at baseline. Flow was demonstrated in 93.9% of treated vessels and compressibility in 96.2% via duplex ultrasound assessment. Further significant improvements were observed in revised Venous Clinical Severity Score, Numeric Pain Rating Scale, and EQ-5D scores when compared to baseline. These real-world data detailing MT for DVT outcomes with the ClotTriever System demonstrate significant symptom relief and quality-of-life improvement for patients in addition to recovery of vessel function and a low rate of subsequent PTS. Such favorable long-term outcomes coupled with previously reported acute safety and effectiveness profiles support MT treatment for DVT. Definitive evidence comparing MT plus anticoagulation to anticoagulation alone will come from the currently enrolling DEFIANCE randomized controlled trial (NCT05701917). About the VIVA Foundation The VIVA Foundation, a not-for-profit organization dedicated to advancing the field of vascular medicine and intervention through education and research, strives to be the premier educator in the field. Our team of specialists in vascular medicine, interventional cardiology, interventional radiology, and vascular surgery is driven by the passion to advance the field and improve patient outcomes. Educational events presented by the VIVA Foundation have a distinct spirit of collegiality attained by synergizing collective talents to promote awareness and innovative therapeutic options for vascular disease worldwide. To learn more about the VIVA Foundation, visit . Media contact: [email protected] SOURCE The VIVA Foundation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

THOUSAND OAKS, Calif., Oct. 30, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the third quarter of 2024. "Strong growth in sales and earnings this quarter reflects the momentum we're building throughout our business. We continue to invest heavily in our rapidly advancing pipeline, with a focus on delivering innovative therapies across our core therapeutic areas," said Robert A. Bradway, chairman and chief executive officer. Key results include: For the third quarter, total revenues increased 23% to $8.5 billion in comparison to the third quarter of 2023. Product sales grew 24%, driven by 29% volume growth, partially offset by 2% lower net selling price. Excluding sales from our Horizon Therapeutics (Horizon) acquisition, product sales grew 8%, driven by volume growth of 12%. Ten products delivered at least double-digit sales growth in the third quarter, including Repatha® (evolocumab), TEZSPIRE® (tezepelumab-ekko), BLINCYTO® (blinatumomab), EVENITY® (romosozumab-aqqg), and TAVNEOS® (avacopan). Our performance included $1.2 billion of sales from our rare disease products, driven by several first-in-class, early-in-lifecycle medicines, including TEPEZZA® (teprotumumab-trbw), KRYSTEXXA® (pegloticase), UPLIZNA® (inebilizumab-cdon), and TAVNEOS® (avacopan). GAAP earnings per share (EPS) increased 62% from $3.22 to $5.22, driven by mark-to-market gains on our BeiGene, Ltd. (BeiGene) equity investment and higher revenues, partially offset by higher operating expenses, including amortization expense from Horizon-acquired assets and incremental expenses from Horizon. GAAP operating income remained relatively unchanged at $2.0 billion, and GAAP operating margin decreased 5.8 percentage points to 25.1%. Non-GAAP EPS increased 13% from $4.96 to $5.58, driven by higher revenues, partially offset by higher operating expenses, including incremental expenses from Horizon, and interest expense. Non-GAAP operating income increased from $3.4 billion to $4.0 billion, and non-GAAP operating margin decreased 2.4 percentage points to 49.6%. The Company generated $3.3 billion of free cash flow in the third quarter of 2024 versus $2.5 billion in the third quarter of 2023, driven by business performance and timing of working capital items, partially offset by lower interest income. References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis" and "free cash flow" (computed by subtracting capital expenditures from operating cash flow) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion. Product Sales Performance General Medicine Repatha® (evolocumab) sales increased 40% year-over-year to $567 million in the third quarter, driven by 41% volume growth and 8% favorable changes to estimated sales deductions, partially offset by 10% lower net selling price. EVENITY® (romosozumab-aqqg) sales increased 30% year-over-year to $399 million in the third quarter, driven by volume growth. Prolia® (denosumab) sales increased 6% year-over-year to $1.0 billion in the third quarter, driven by 9% volume growth, partially offset by lower inventory levels. Oncology BLINCYTO® (blinatumomab) sales increased 49% year-over-year to $327 million in the third quarter, primarily driven by volume growth. Vectibix® (panitumumab) sales increased 12% year-over-year to $282 million in the third quarter, primarily driven by volume growth. KYPROLIS® (carfilzomib) sales increased 8% year-over-year to $378 million in the third quarter, primarily driven by volume growth outside the U.S. LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 88% year-over-year to $98 million in the third quarter, driven by volume growth and favorable changes to estimated sales deductions. XGEVA® (denosumab) sales increased 4% year-over-year to $541 million in the third quarter, driven by higher net selling price. Nplate® (romiplostim) sales increased 9% year-over-year to $456 million in the third quarter. U.S. government orders were $128 million in Q3'24 compared to $142 million in Q3'23. Excluding these U.S. government orders, Nplate sales grew 18% year-over-year in the third quarter, driven by 14% volume growth and higher net selling price. IMDELLTRA™ (tarlatamab-dlle) generated $36 million of sales in the third quarter. Sales increased 200% quarter-over-quarter, driven by volume growth. IMDELLTRA is the first and only FDA-approved bispecific T-cell engager (BiTE ®) therapy for the treatment of extensive-stage small cell lung cancer (ES-SCLC). MVASI® (bevacizumab-awwb) sales decreased 8% year-over-year to $195 million in the third quarter. Going forward, we expect continued sales erosion driven by competition. Inflammation TEZSPIRE® (tezepelumab-ekko) sales increased 67% year-over-year to $269 million in the third quarter, driven by volume growth. Otezla® (apremilast) sales decreased 1% year-over-year to $564 million in the third quarter, primarily driven by 7% lower net selling price, partially offset by 5% volume growth. Enbrel® (etanercept) sales decreased 20% year-over-year to $825 million in the third quarter, primarily driven by 13% unfavorable changes to estimated sales deductions and 12% lower net selling price. Going forward, we expect continued declining net selling price and relatively flat volumes. AMJEVITA®/AMGEVITA™ (adalimumab) sales increased 9% year-over-year to $166 million in the third quarter. Rare Disease Except for TAVNEOS®, the products listed below were added through the acquisition of Horizon on Oct. 6, 2023. TEPEZZA® (teprotumumab-trbw) generated $488 million of sales in the third quarter. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED). KRYSTEXXA® (pegloticase) generated $310 million of sales in the third quarter. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout. UPLIZNA® (inebilizumab-cdon) generated $106 million of sales in the third quarter. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorder. TAVNEOS® (avacopan) generated $80 million of sales in the third quarter. Sales increased 116% year-over-year, primarily driven by volume growth. TAVNEOS is a first-in-class treatment for severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis). Ultra-Rare products, which consist of RAVICTI® (glycerol phenylbutyrate), PROCYSBI® (cysteamine bitartrate), ACTIMMUNE® (interferon gamma-1b), QUINSAIR® (levofloxacin) and BUPHENYL® (sodium phenylbutyrate), generated $188 million of sales in the third quarter. Established Products Our established products, which consist of EPOGEN® (epoetin alfa), Aranesp® (darbepoetin alfa), Parsabiv® (etelcalcetide) and Neulasta® (pegfilgrastim), generated $550 million of sales. Sales decreased 7% year-over-year for the third quarter, driven by volume declines. In the aggregate, we expect the year-over-year volume declines for this portfolio of products to continue. Product Sales Detail by Product and Geographic Region Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis for the third quarter: Total Operating Expenses increased 32% year-over-year. Cost of Sales as a percentage of product sales increased 13.0 percentage points driven by higher amortization expense from Horizon acquisition-related assets and, to a lesser extent, higher royalties and profit share. Research & Development (R&D) expenses increased 34% driven by higher spend in later-stage clinical programs, marketed product support, and research and early pipeline, including Horizon-acquired programs. Selling, General & Administrative (SG&A) expenses increased 20% primarily driven by commercial expenses related to Horizon-acquired products. Other operating expenses consisted primarily of an impairment charge associated with an IPR&D asset and changes in the fair values of contingent consideration liabilities, both related to our Teneobio, Inc. acquisition from 2021. Operating Margin as a percentage of product sales decreased 5.8 percentage points year-over-year to 25.1%. Tax Rate decreased 2.4 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business, partially offset by quarter-to-date 2024 unrealized gains on our strategic equity investments, primarily BeiGene. On a non-GAAP basis for the third quarter: Total Operating Expenses increased 27% year-over-year. Cost of Sales as a percentage of product sales increased 0.4 percentage points driven by higher royalties and profit share, partially offset by lower manufacturing costs and changes in sales mix. R&D expenses increased 35% driven by higher spend in later-stage clinical programs, marketed product support, and research and early pipeline, including Horizon-acquired programs. SG&A expenses increased 21%, primarily driven by commercial expenses related to Horizon-acquired products. Operating Margin as a percentage of product sales decreased 2.4 percentage points year-over-year to 49.6%. Tax Rate decreased 2.7 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business. Cash Flow and Balance Sheet The Company generated $3.3 billion of free cash flow in the third quarter of 2024 versus $2.5 billion in the third quarter of 2023, driven by business performance and timing of working capital items, partially offset by lower interest income. The Company's third quarter 2024 dividend of $2.25 per share was declared on August 2, 2024, and was paid on September 6, 2024, to all stockholders of record as of August 16, 2024, representing a 6% increase from this same period in 2023. During the third quarter, the Company reduced principal debt outstanding by $2.5 billion. Year-to-date, the Company has reduced principal debt outstanding by $4.5 billion. Cash and investments totaled $9.0 billion and debt outstanding totaled $60.4 billion as of September 30, 2024. 2024 Guidance For the full year 2024, the Company now expects: Total revenues in the range of $33.0 billion to $33.8 billion. On a GAAP basis, EPS in the range of $8.71 to $9.56, and a tax rate in the range of 9.0% to 10.5%. On a non-GAAP basis, EPS in the range of $19.20 to $20.00, and a tax rate in the range of 14.0% to 15.0%. Capital expenditures to be approximately $1.3 billion. Share repurchases not to exceed $500 million. Third Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine MariTide (maridebart cafraglutide, AMG 133) MariTide is a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor. A Phase 2 study of MariTide is ongoing in adults who are living with overweight or obesity, with or without Type 2 diabetes mellitus. Topline data are anticipated in late 2024. Planning for a broad Phase 3 program across multiple indications remains on track. A Phase 2 study investigating MariTide was initiated for the treatment of Type 2 diabetes in patients with and without obesity. AMG 513 A Phase 1 study of AMG 513 was initiated and is enrolling patients living with obesity. Olpasiran (AMG 890) Olpasiran is a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver. The Ocean(a)-Outcomes trial, a Phase 3 cardiovascular outcomes study, is ongoing in patients with atherosclerotic cardiovascular disease and elevated Lp(a). Repatha EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular (CV) events, is ongoing. VESALIUS-CV, a Phase 3 CV outcomes study of Repatha, is ongoing in patients at high CV risk without prior myocardial infarction or stroke. In September data were presented from: a sub-analysis of the FOURIER trial demonstrating that patients with obesity (BMI >35) are at an increased risk of CV events. Repatha treatment of patients with obesity resulted in a reduction in the composite endpoint of CV death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization at 3 years [HR 0.71 (0.59-0.86), and Absolute Risk Reduction = 5.65%] the SLICE-CEA study, the first randomized trial of Repatha in patients with asymptomatic severe high-risk carotid artery stenosis. The study demonstrated that 6 months of Repatha treatment led to significant reductions in lipid rich necrotic core (LRNC) volume (p=0.017) and its components, intraplaque hemorrhage (IPH) (p=0.037) and lipid volume (p=0.023) in the carotid vessels, as assessed by MRI. Oncology IMDELLTRA IMDELLTRA is a first-in-class delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule. The Company is advancing a comprehensive global clinical development program across extensive-stage and limited-stage small cell lung cancer (SCLC): DeLLphi-304, a Phase 3 study comparing IMDELLTRA with standard of care chemotherapy in second-line extensive-stage small cell lung cancer (ES-SCLC), is ongoing. DeLLphi-305, a Phase 3 study comparing IMDELLTRA and durvalumab with durvalumab alone, is enrolling patients with first-line ES-SCLC. DeLLphi-306, a Phase 3 study comparing IMDELLTRA with placebo following concurrent chemoradiation therapy, is enrolling patients with limited-stage SCLC. DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab, was initiated in patients with second line or later ES-SCLC. DeLLphi-303, a Phase 1b study of IMDELLTRA in combination with a programmed cell death protein ligand-1 (PD-L1) inhibitor +/- carboplatin and etoposide, is ongoing in patients with first-line ES-SCLC. DeLLphi-302, a Phase 1b study of IMDELLTRA in combination with AMG 404 in patients with second-line or later SCLC, is complete. AMG 404 is an anti-programmed cell death protein 1 (PD1) monoclonal antibody. DeLLpro-300, a Phase 1b study of IMDELLTRA in patients with previously treated de novo or treatment-emergent neuroendocrine prostate cancer, is complete. In September, data were presented from: DeLLphi-301, a Phase 2 study of IMDELLTRA where extended follow-up data demonstrated sustained anti-cancer activity and a manageable safety profile in patients with ES-SCLC previously treated with platinum-based chemotherapy. Among 100 patients treated with the 10 mg dose level, the median duration of response was 9.7 months (95% CI, 6.9‒NE) and the median overall survival was 15.2 months. No new safety concerns were identified. DeLLphi-303, a Phase 1b study of IMDELLTRA combined with a PD-L1 inhibitor as first-line ES-SCLC maintenance therapy. With a median follow-up of 10.0 months (range 1.4 - 20.4), IMDELLTRA in combination with a PD-L1 inhibitor, demonstrated a manageable safety profile with durable disease control [median duration of disease control: 9.3 months (95% CI: 5.6–not estimable)] and notable survival outcomes [median PFS 5.6 months (95% CI: 3.6–9.0), 9-month Kaplan-Meier estimate for OS of 88.9%]. BLINCYTO Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy, continues to enroll older adult patients with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell precursor acute lymphoblastic leukemia (B-ALL). A Phase 1/2 study of subcutaneous blinatumomab has completed enrollment in the dose-expansion and optimization phase in adult patients with relapsed or refractory Ph-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025. Xaluritamig (AMG 509) Xaluritamig is a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1). The Company will initiate a Phase 3 study in post-taxane metastatic castrate resistant prostate cancer (mCRPC) in fourth quarter of 2024. A Phase 1 monotherapy dose-expansion study of xaluritamig is ongoing in patients with mCRPC and has completed enrollment of patients in a reduced monitoring after treatment administration cohort. A fully outpatient treatment cohort continues to enroll patients to further improve administration convenience. A Phase 1 combination of xaluritamig with enzalutamide or abiraterone continues to enroll patients with mCRPC in dose-escalation and dose-expansion respectively. A Phase 1b study evaluating neoadjuvant xaluritamig therapy prior to radical prostatectomy was initiated in patients with newly diagnosed localized intermediate or high–risk prostate cancer. A Phase 1b study was initiated and is now enrolling patients to evaluate xaluritamig in patients with high-risk nonmetastatic hormone-sensitive prostate cancer after definitive therapy. In September results were presented from: a Phase 1 dose exploration cohort evaluating xaluritamig monotherapy in patients with mCRPC where with a median follow-up of 27.9 months, the median OS was 17.7 months across all cohorts. An encouraging PSA90 rate (45.1%) was also observed in high-dose cohorts, and presence of PSA90 response was associated with survival (p = 0.0044), potentially serving as an early indicator for benefit in these patients. a Phase 1 dose-expansion cohort evaluating xaluritamig monotherapy using multiple dosing regimens in patients with mCRPC demonstrated that the 1.5 mg Q2W target dosing regimen is the most favorable efficacy and safety profile and will be the recommended Phase 3 dose and schedule. AMG 193 AMG 193 is a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. A Phase 1/1b/2 study of AMG 193 continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors in the dose-expansion portion of the study. A Phase 1b study of AMG 193 alone or in combination with other therapies is enrolling patients with advanced MTAP-null thoracic malignancies. A Phase 1b study of AMG 193 in combination with other therapies in advanced MTAP-null gastrointestinal, biliary tract, and pancreatic cancers is enrolling patients. A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, continues to enroll patients with advanced MTAP-null solid tumors. A Phase 2 study evaluating the efficacy, safety, tolerability, and pharmacokinetics of AMG 193 was initiated in patients with MTAP-null previously treated advanced non-small cell lung cancer (NSCLC). In September, data were presented from a Phase 1 dose-escalation and initial dose-expansion study of AMG 193 in patients with MTAP-null solid tumors. The data demonstrated monotherapy activity and an acceptable safety profile. These data open opportunities to explore both monotherapy and combination therapy development strategies. Bemarituzumab Bemarituzumab is a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody. FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, is ongoing in patients with first-line gastric cancer. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in patients with first-line gastric cancer, has completed enrollment of the Phase 3 portion of the study. FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab, continues to enroll patients in first-line gastric cancer. FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy, is ongoing in patients with solid tumors with FGFR2b overexpression. Nplate The primary analysis of a Phase 3 study of Nplate as supportive care in chemotherapy-induced thrombocytopenia in gastrointestinal malignancies is complete. The Company continues to follow patients through a planned final analysis in H1 2025. Data presentation at a medical congress is anticipated in mid-2025. LUMAKRAS/LUMYKRAS CodeBreaK 202, a Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy, is enrolling patients with first-line KRAS G12C–mutated and programmed PD-L1 negative advanced NSCLC. Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 study of adults with previously treated locally advanced or metastatic KRAS G12C–mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing. The U.S Food and Drug Administration (FDA) extended the Prescription Drug User Fee Act (PDUFA) date for the Phase 3 CodeBreaK 300 study of LUMAKRAS plus Vectibix vs. investigator's choice of therapy in KRAS G12C–mutated metastatic colorectal cancer (CRC) from October 17, 2024, to January 17, 2025, to allow time for review of recently submitted supplemental data. CodeBreaK 301, a Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI, is enrolling patients with first-line KRAS G12C–mutated CRC. Inflammation TEZSPIRE The Company is planning to initiate Phase 3 studies in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) and a BEC ≥ 150 cells/µl or greater. Study initiation is anticipated in H1 2025. A Phase 3 study of TEZSPIRE is ongoing in patients with chronic rhinosinusitis with nasal polyps. Data readout is anticipated in H2 2024. A Phase 3 study of TEZSPIRE continues to enroll patients with eosinophilic esophagitis. In severe asthma, the WAYFINDER Phase 3b study and the PASSAGE Phase 4 real-world effectiveness study are fully enrolled. The SUNRISE Phase 3 study continues to enroll patients. Rocatinlimab (AMG 451/KHK4083) Rocatinlimab is a first-in-class T-cell rebalancing monoclonal antibody targeting the OX40 receptor. The eight study ROCKET Phase 3 program continues to enroll patients with moderate-to-severe atopic dermatitis (AD). To date, over 3,200 patients have been enrolled in the ROCKET program, with six studies having completed enrollment. In September, the Company reported results from the Phase 3 HORIZON study (part of the ROCKET program), evaluating rocatinlimab monotherapy vs. placebo in adults with moderate-to-severe AD. The study met its co-primary endpoints and all key secondary endpoints, achieving statistical significance versus placebo at week 24. 32.8% of patients in the rocatinlimab group achieved ≥ 75% reduction from baseline in Eczema Area and Severity Index score (EASI-75), compared to 13.7% placebo treated (19.1% difference, p<0.001). 19.3% of patients in the rocatinlimab group achieved a Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-ADTM) score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline, compared to 6.6% in placebo (12.8% difference, p<0.001). In the U.S., a more stringent scoring method was used (revised Investigator's Global Assessment, or rIGA) where 16.4% of patients in the rocatinlimab group achieved a score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline, compared to 4.9% in placebo (11.5% difference, p<0.001). Safety findings were consistent with those seen in the Phase 2b AD study. Additional key data readouts from the ROCKET Phase 3 program are expected in late 2024 through H2 2025: ROCKET SHUTTLE is a 24-week study evaluating rocatinlimab in combination with topical corticosteroids and/or topical calcineurin inhibitors in adult patients with moderate-to-severe AD. Data readout is anticipated in late 2024 to early 2025. ROCKET IGNITE is a 24-week study evaluating rocatinlimab monotherapy in adult patients with moderate-to-severe AD. Data readout is anticipated in late 2024 to early 2025. ROCKET ASCEND is a study evaluating rocatinlimab maintenance therapy in adult and adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. ROCKET ASTRO is a 52-week study evaluating rocatinlimab in adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. A Phase 2 study of rocatinlimab is enrolling patients with moderate-to-severe asthma. A Phase 3 study of rocatinlimab is enrolling patients with prurigo nodularis. Otezla In September data were presented from: a Phase 3 study of Japanese patients with Palmoplantar Pustulosis (PPP) demonstrating maintained or increased efficacy (compared with the week 16 primary analysis) and no new safety signals with 52 weeks of Otezla treatment. the DISCREET moderate-to-severe genital psoriasis study demonstrating that improvements in disease severity, symptoms, and quality of life with Otezla treatment were maintained at week 32. No new safety signals were observed. the FOREMOST study of patients with oligoarticular psoriatic arthritis, where Otezla demonstrated sustained benefits in skin, joint, fatigue, and pain symptoms through 48-weeks. Blinatumomab Blinatumomab is a bispecific T-cell engager (BiTE) molecule targeting CD19. A Phase 2 study of blinatumomab was initiated in patients with autoimmune disease with an initial focus on systemic lupus erythematosus (SLE) with nephritis. Inebilizumab Inebilizumab is a monoclonal antibody targeting CD19. A Phase 2 study of inebilizumab was initiated in patients with autoimmune disease with an initial focus on SLE with nephritis. Efavaleukin alfa (AMG 592) Efavaleukin alfa is an interleukin 2 (IL 2) mutein Fc fusion protein. A Phase 2b study of efavaleukin alfa in patients with ulcerative colitis was terminated due to the study meeting a prespecified futility threshold, and not related to safety concerns. Ordesekimab (AMG 714/PRV-015) Ordesekimab is a monoclonal antibody that binds interleukin-15. A Phase 2b study of ordesekimab is ongoing in patients with nonresponsive celiac disease. AMG 104 (AZD8630) AMG 104 is an inhaled anti-thymic stromal lymphopoietin (TSLP) fragment antigen-binding (Fab). A Phase 2 study was initiated in patients with asthma. Rare Disease TAVNEOS A Phase 3, open-label study of TAVNEOS in combination with Rituximab or a cyclophosphamide-containing regimen, is enrolling patients from 6 years to < 18 years of age with active ANCA-associated vasculitis (Granulomatosis with Polyangiitis (GPA) / Microscopic Polyangiitis (MPA)). TEPEZZA In September, TEPEZZA was approved for the treatment of active Thyroid Eye Disease (TED) by Japan's Ministry of Health, Labour and Welfare (MHLW). Regulatory review in multiple additional geographies continues. A Phase 3 study of TEPEZZA in Japan continues to enroll patients with chronic or low clinical activity score TED. A Phase 3 study evaluating the subcutaneous route of administration of teprotumumab is enrolling patients with TED. KRYSTEXXA Data from the AGILE study evaluating the safety, tolerability, and efficacy of KRYSTEXXA administered with a shorter infusion duration in patients with uncontrolled gout receiving methotrexate as co-administration will be presented at the American College of Rheumatology Convergence (ACR) in November. UPLIZNA The Company recently presented results of the Phase 3 MINT clinical study evaluating the efficacy and safety of UPLIZNA for the treatment of generalized myasthenia gravis (gMG). UPLIZNA demonstrated a clinically meaningful and statistically significant Myasthenia Gravis Activities of Daily Living (MG-ADL) score improvement after two doses compared to placebo at Week 26: -4.2 overall improvement, -1.9 placebo adjusted (p < 0.0001, primary endpoint). In the acetylcholine receptor autoantibody-positive (AChR+) population, UPLIZNA demonstrated a clinically meaningful and statistically significant MG-ADL score improvement compared to placebo at Week 26: -4.2 overall improvement, -1.8 placebo adjusted (p = 0.0015, secondary endpoint). In the muscle-specific kinase autoantibody-positive (MuSK+) population, UPLIZNA demonstrated a clinically meaningful and statistically significant MG-ADL score improvement compared to placebo at Week 26: -3.9 overall improvement, -2.2 placebo adjusted (p = 0.0297, secondary endpoint). UPLIZNA demonstrated a statistically significant Quantitative Myasthenia Gravis (QMG) score improvement after two doses compared to placebo at week 26: -4.8 overall improvement, -2.5 placebo adjusted (p = 0.0002, secondary endpoint). In the AChR+ population, UPLIZNA demonstrated a clinically meaningful and statistically significant QMG score improvement compared to placebo at week 26: -4.4 overall improvement, -2.5 placebo adjusted (p = 0.0011, secondary endpoint). In the MuSK+ population, the mean change from baseline in QMG score at Week 26 showed a trend favoring UPLIZNA but was not statistically significant (-5.2 for UPLIZNA and -3.0 for placebo, difference -2.3, p=0.1326). Patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24. The overall safety results during the placebo-controlled period of the study were consistent with the known safety profile of UPLIZNA. 52-week data from the AChR+ cohort and from AChR+ and MuSK+ patients in the open-label period of the study will be presented at a future date. Planning for regulatory submissions for gMG is underway. In August, the FDA granted Breakthrough Therapy Designation for UPLIZNA in the treatment of Immunoglobulin G4-related diseases (IgG4-RD) based upon data from the Phase 3 MITIGATE study. Regulatory filing activities for IgG4-RD are underway. MITIGATE results will be presented at ACR in November. Dazodalibep Dazodalibep is a fusion protein that inhibits CD40L. Two Phase 3 studies of dazodalibep in Sjögren's disease are enrolling patients. The first study is in patients with moderate-to-severe systemic disease activity, and the second study is in patients with moderate-to-severe symptomatic burden and low systemic disease activity. Daxdilimab Daxdilimab is a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7). A Phase 2 study of daxdilimab is ongoing in patients with moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care. A Phase 2 study of daxdilimab is ongoing in patients with dermatomyositis and antisynthetase inflammatory myositis. Fipaxalparant Fipaxalparant is a lysophosphatidic acid receptor 1 (LPAR1) antagonist. A Phase 2 study of fipaxalparant in patients with idiopathic pulmonary fibrosis is complete. The study did not meet any of the primary or secondary endpoints. Development of fipaxalparant in this indication will be discontinued. A Phase 2 study of fipaxalparant has completed enrollment of patients with diffuse cutaneous systemic sclerosis. Biosimilars In August, the FDA approved PAVBLUTM (aflibercept-ayyh) (ABP 938), a biosimilar candidate to EYLEA® (aflibercept), for the treatment of retinal conditions, including neovascular age-related macular degeneration (wet AMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy. A randomized, double-blind pharmacokinetic similarity study of ABP 206 compared with OPDIVO® (nivolumab) is enrolling patients with resected stage III or stage IV melanoma in the adjuvant setting. A randomized, double-blind comparative clinical study of ABP 206 compared with OPDIVO is enrolling patients with treatment-naïve unresectable or metastatic melanoma. A randomized, double-blind combined pharmacokinetic/comparative clinical study of ABP 234 compared to KEYTRUDA® (pembrolizumab) is enrolling patients with advanced or metastatic non-squamous non-small cell lung cancer. TEZSPIRE is being developed in collaboration with AstraZeneca. AMG 104 is being developed in collaboration with AstraZeneca. Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin. Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program. Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc. IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences. EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. OPDIVO is a registered trademark of Bristol-Myers Squibb Company. KEYTRUDA is a registered trademark of Merck & Co., Inc. Non-GAAP Financial Measures In this news release, management has presented its operating results for the third quarters of 2024 and 2023, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2024 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the third quarters of 2024 and 2023. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.  Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED