On October 28, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai reported that the Phase 3 LITESPARK-011 trial evaluating the dual oral regimen of WELIREG (belzutifan), Merck’s first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, plus LENVIMA (lenvatinib), an orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, met one of its primary endpoints of progression-free survival (PFS) for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease progressed on or after treatment with anti-PD-1/L1 therapy.

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At a pre-specified interim analysis, WELIREG plus LENVIMA demonstrated a statistically significant and clinically meaningful improvement in PFS compared to cabozantinib in these patients. The combination also showed a statistically significant improvement in the trial’s key secondary endpoint of objective response rate (ORR) compared to cabozantinib. A trend toward improvement in overall survival (OS), the study’s other primary endpoint, was observed; however, this result did not reach statistical significance at the time of this interim analysis. Overall survival will be tested at a subsequent analysis, per the clinical protocol.

The safety profiles of WELIREG and LENVIMA in this trial were consistent with those observed in previously reported studies for the individual therapies; no new safety signals were observed. Merck and Eisai will discuss these data with regulatory authorities worldwide and will present them at an upcoming medical meeting.

"Despite recent treatment advances, many patients with advanced RCC may still experience disease progression following treatment with a PD-1/L1 inhibitor," said Dr. M. Catherine Pietanza, Vice President, Global Clinical Development, Merck Research Laboratories. "These positive results from LITESPARK-011 show the potential of this novel combination to reduce the risk of disease progression or death for patients who are in need of innovative options on or after treatment with immunotherapy."

"We are encouraged by the data observed in the LITESPARK-011 trial, which bolster our belief in the role of LENVIMA in various combinations as a treatment option for patients impacted by advanced RCC," said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai. "These results further demonstrate Eisai’s commitment to people living with advanced RCC and invigorate our mission to address the unmet needs of patients with difficult-to-treat cancers. We look forward to sharing these investigational findings with regulatory authorities worldwide, with the goal of bringing this treatment option to patients as soon as possible. We extend our heartfelt gratitude to the patients, caregivers and investigators for their participation in this study, and for helping us move this important research forward."

LITESPARK-011 is part of a comprehensive late-stage clinical development program for WELIREG comprised of several Phase 2 and Phase 3 trials in RCC, pheochromocytoma and paraganglioma, and von Hippel-Lindau disease-associated neoplasms. The Phase 3 LITESPARK-012 trial is evaluating the addition of WELIREG to KEYTRUDA (pembrolizumab) plus LENVIMA in the first-line advanced RCC disease setting.

WELIREG is approved in the U.S., European Union (EU), Japan, and other countries for the treatment of adult patients with advanced clear cell RCC following a PD-1/PD-L1 inhibitor and 1-2 VEGF-TKIs, based on results from the Phase 3 LITESPARK-005 trial.

KEYTRUDA plus LENVIMA is approved in the U.S., the EU, Japan and other countries for the treatment of advanced RCC and certain types of advanced endometrial carcinoma. Lenvatinib is approved as KISPLYX for advanced RCC in the EU.

LENVIMA in combination with everolimus is approved in the U.S., EU and other regions for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy.

About LITESPARK-011

LITESPARK-011 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT04586231) evaluating WELIREG in combination with LENVIMA compared to cabozantinib for the treatment of patients with advanced clear cell RCC that has progressed on or after anti-PD-1/L1 therapy. The dual primary endpoints are PFS per RECIST v1.1 as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include ORR per RECIST v1.1 as assessed by BICR, duration of response (DOR) per RECIST v1.1 as assessed by BICR, and safety. The trial enrolled an estimated 708 patients who were randomized to receive WELIREG (120 mg orally once daily) plus LENVIMA (20 mg orally once daily) or cabozantinib (60 mg orally once daily).

About renal cell carcinoma

Renal cell carcinoma is the most common type of kidney cancer, with about nine out of 10 kidney cancer diagnoses being RCC. In 2022, there were about 435,000 new cases of kidney cancer diagnoses and approximately 156,000 deaths from the disease worldwide. RCC is about twice as common in men as in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with kidney cancer are diagnosed at an advanced stage.

About WELIREG (belzutifan) 40 mg tablets, for oral use

Indications in the U.S.

Certain von Hippel-Lindau (VHL) disease-associated tumors

WELIREG is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Advanced Renal Cell Carcinoma (RCC)

WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) with a clear cell component following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

Pheochromocytoma or Paraganglioma (PPGL)

WELIREG is indicated for the treatment of adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL).

Selected Safety Information for WELIREG

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

Anemia

WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG.

In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months).

The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established.

In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC with a clear cell component and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs.

In LITESPARK-015, anemia occurred in 96% of patients and 22% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 22.1 months). Of the patients with anemia, 20% received transfusions only, 26% received ESAs only, and 6% received both transfusion and ESAs.

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.

Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same dose or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening hypoxia or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

In LITESPARK-004, hypoxia occurred in 1.6% of patients.

In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months).

In LITESPARK-015, hypoxia occurred in 13% of patients and 10% had Grade 3 hypoxia. Median time to onset of hypoxia was 35 days (range: 6 days to 23.9 months). Of the patients with hypoxia, 67% were treated with oxygen therapy.

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

Adverse Reactions in LITESPARK-004

Serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

Adverse Reactions in LITESPARK-005

Serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%).

WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%), anemia (0.5%), and hemorrhage (0.5%).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%).

Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (34%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%).

Adverse Reactions in LITESPARK-015

Serious adverse reactions occurred in 36% of patients. The most frequently reported serious adverse reactions were anemia and hypertension (4.2% each) and pyelonephritis, pneumonia, hypoxia, dyspnea and hemorrhage (2.8% each)

WELIREG was permanently discontinued due to adverse reactions in 2 patients (2.8%). Adverse reactions which resulted in permanent discontinuation were increased alanine aminotransferase and paraparesis (1.4% each).

Dosage interruptions due to an adverse reaction occurred in 40% of patients. Of the patients who received WELIREG, 13% were ≥65 years old and 4.2% were ≥75 years. Adverse reactions which required dosage interruption in >3% of patients were hypoxia, nausea and fatigue (4.2% each).

Dose reductions due to an adverse reaction occurred in 14% of patients. The most frequently reported adverse reaction which required dose reduction was hypoxia (4.2%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, that occurred in patients were anemia (96%), fatigue (56%), musculoskeletal pain (56%), decreased lymphocytes (54%), increased alanine aminotransferase (51%), increased aspartate aminotransferase (42%), increased calcium (34%), dyspnea (33%), increased potassium (31%), decreased leukocytes (30%), headache (29%), increased alkaline phosphatase (25%), dizziness (26%) and nausea (25%).

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

The safety and effectiveness of WELIREG have been established in pediatric patients aged 12 years and older for the treatment of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma.

Renal Impairment

For patients with severe renal impairment (eGFR 15-29 mL/min estimated by MDRD), monitor for increased adverse reactions and modify the dosage as recommended.

Hepatic Impairment

WELIREG has not been studied in patients with severe hepatic impairment (total bilirubin >1.5 x ULN and any AST). For patients with moderate and severe hepatic impairment, monitor for increased adverse reactions and modify the dosage as recommended.

Please see Prescribing Information, including information for the Boxed Warning about embryo-fetal toxicity, for WELIREG (belzutifan) at View Source and Medication Guide for WELIREG at View Source

About LENVIMA (lenvatinib); available as 10 mg and 4 mg capsules

LENVIMA, discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

LENVIMA (lenvatinib) Indications in the U.S.

For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).
In combination with pembrolizumab, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy.
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).
In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Selected Safety Information for LENVIMA

Warnings and Precautions

Hypertension. In differentiated thyroid cancer (DTC), hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In advanced renal cell carcinoma (RCC), hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In unresectable hepatocellular carcinoma (HCC), hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.

Among patients receiving LENVIMA with KEYTRUDA, arterial thrombotic events of any severity occurred in 5% of patients in CLEAR, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).

Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established.

Osteonecrosis of the Jaw (ONJ). ONJ has been reported in patients receiving LENVIMA. Concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease or invasive dental procedures, may increase the risk of ONJ.

Perform an oral examination prior to treatment with LENVIMA and periodically during LENVIMA treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with LENVIMA and throughout treatment with LENVIMA.

Avoid invasive dental procedures, if possible, while on LENVIMA treatment, particularly in patients at higher risk. Withhold LENVIMA for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ.

Withhold LENVIMA if ONJ develops and restart based on clinical judgement of adequate resolution.

Embryo‐Fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of LENVIMA during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for 30 days after the last dose.

Adverse Reactions

In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥20%) observed in LENVIMA + KEYTRUDA-treated patients were fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), decreased weight (30%), dysphonia (30%), proteinuria (30%), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain (27%), hemorrhagic events (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%). Fatal adverse reactions occurred in 4.3% of patients receiving LENVIMA in combination with KEYTRUDA, including cardio-respiratory arrest (0.9%), sepsis (0.9%), and one case (0.3%) each of arrhythmia, autoimmune hepatitis, dyspnea, hypertensive crisis, increased blood creatinine, multiple organ dysfunction syndrome, myasthenic syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm and subarachnoid hemorrhage. Serious adverse reactions occurred in 51% of patients receiving LENVIMA and KEYTRUDA. Serious adverse reactions in ≥2% of patients were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%). Permanent discontinuation of LENVIMA, KEYTRUDA, or both due to an adverse reaction occurred in 37% of patients; 26% LENVIMA only, 29% KEYTRUDA only, and 13% both drugs. The most common adverse reactions (≥2%) leading to permanent discontinuation of LENVIMA, KEYTRUDA, or both were pneumonitis (3%), myocardial infarction (3%), hepatotoxicity (3%), acute kidney injury (3%), rash (3%), and diarrhea (2%). Dose interruptions of LENVIMA, KEYTRUDA, or both due to an adverse reaction occurred in 78% of patients receiving LENVIMA in combination with KEYTRUDA. LENVIMA was interrupted in 73% of patients and both drugs were interrupted in 39% of patients. LENVIMA was dose reduced in 69% of patients. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were diarrhea (26%), fatigue (18%), hypertension (17%), proteinuria (13%), decreased appetite (12%), palmar-plantar erythrodysesthesia (11%), nausea (9%), stomatitis (9%), musculoskeletal pain (8%), rash (8%), increased lipase (7%), abdominal pain (6%), vomiting (6%), increased ALT (5%), and increased amylase (5%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

In endometrial carcinoma, the most common adverse reactions (≥20%) observed in LENVIMA + KEYTRUDA-treated patients were hypothyroidism (67%), hypertension (67%), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), decreased weight (34%), abdominal pain (34%), urinary tract infection (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar‐plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%). Fatal adverse reactions among these patients occurred in 4.7% of those treated with LENVIMA and KEYTRUDA, including 2 cases of pneumonia, and 1 case of the following: acute kidney injury, acute myocardial infarction, colitis, decreased appetite, intestinal perforation, lower gastrointestinal hemorrhage, malignant gastrointestinal obstruction, multiple organ dysfunction syndrome, myelodysplastic syndrome, pulmonary embolism, and right ventricular dysfunction. Serious adverse reactions occurred in 50% of these patients receiving LENVIMA and KEYTRUDA. Serious adverse reactions with frequency ≥3% were hypertension (4.4%), and urinary tract infection (3.2%). Discontinuation of LENVIMA due to an adverse reaction occurred in 26% of these patients. The most common (≥1%) adverse reactions leading to discontinuation of LENVIMA were hypertension (2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%), proteinuria (1.2%), and vomiting (1.2%). Dose reductions of LENVIMA due to adverse reactions occurred in 67% of patients. The most common (≥5%) adverse reactions resulting in dose reduction of LENVIMA were hypertension (18%), diarrhea (11%), palmar-plantar erythrodysesthesia syndrome (9%), proteinuria (7%), fatigue (7%), decreased appetite (6%), asthenia (5%), and weight decreased (5%). Dose interruptions of LENVIMA due to an adverse reaction occurred in 58% of these patients. The most common (≥2%) adverse reactions leading to interruption of LENVIMA were hypertension (11%), diarrhea (11%), proteinuria (6%), decreased appetite (5%), vomiting (5%), increased alanine aminotransferase (3.5%), fatigue (3.5%), nausea (3.5%), abdominal pain (2.9%), weight decreased (2.6%), urinary tract infection (2.6%), increased aspartate aminotransferase (2.3%), asthenia (2.3%), and palmar-plantar erythrodysesthesia (2%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed children, advise women to discontinue breastfeeding during treatment and for 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (creatinine clearance [CLcr] 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or endometrial carcinoma and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or endometrial carcinoma and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease.

No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended for patients with DTC, RCC, or endometrial carcinoma and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment.

(Press release, Eisai, OCT 28, 2025, View Source [SID1234657065])

On October 28, 2025 Mercy BioAnalytics, Inc., a pioneer in blood-based detection of early-stage cancer, reported the publication of a validation study in the journal of Gynecologic Oncology highlighting the performance of a novel blood test for detection of preclinical early-stage ovarian cancer.

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Led by Mercy researchers in partnership with the Medical Research Council Clinical Trials Unit (MRC CTU) at University College London (UCL), this landmark study represents the first demonstration of a blood test capable of detecting ovarian cancer up to three years prior to diagnosis in prospectively collected preclinical samples from the landmark UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Study Highlights

The blood test achieved 89% sensitivity and 98% specificity for detecting stage I/II high-grade serous carcinoma (HGSC) in average-risk, postmenopausal women, with significantly improved specificity and discrimination compared to CA125.
The blinded evaluation of samples that were prospectively collected prior to cancer diagnosis from the intended use population minimizes bias while demonstrating generalizability of performance.
These findings build upon Mercy’s previous published work validating their blood-based detection technology and establishes the Mercy Halo assay as a promising next-generation screening platform.
The results demonstrate that the test, which detects tumor-derived extracellular vesicles and particles, can identify ovarian cancer with high accuracy—even in preclinical, early-stage disease where intervention is most impactful. These findings suggest the technology has the potential to enable a practical, blood-based screening approach for average-risk women, addressing a critical unmet need in ovarian cancer care. The test’s high specificity minimizes the potential for false positives, while its high early-stage sensitivity enables the detection of ovarian malignancy even before symptoms arise.

"This study marks a watershed moment for noninvasive ovarian cancer screening," said Dawn Mattoon, Ph.D., Chief Executive Officer of Mercy. "Achieving nearly 90% sensitivity with 98% specificity in early-stage disease is unprecedented in this space. We are more confident than ever that our technology can transform how ovarian cancer is detected, offering women a real chance at earlier intervention and improved outcomes."

Ovarian cancer is one of the leading causes of cancer death among women and will kill nearly 13,000 women in the U.S. this year. More than 70% of ovarian cancer is diagnosed in women over 50 years of age, and nearly 80% of ovarian cancer is diagnosed at an advanced stage of disease, when survival is poor. When ovarian cancer is detected early, when disease is still localized, nearly 90% of women survive for ten years or more. Unfortunately, legacy diagnostic test methods have not shown adequate clinical performance to enable broad adoption for ovarian cancer screening.

"This study demonstrates that blood-based biomarkers can provide a highly specific and sensitive signal for early ovarian cancer," said Dr. Usha Menon, Professor of Women’s Cancer at UCL and senior author of the paper. "The blinded evaluation of preclinical samples from the no screening and ultrasound arms of UKCTOCS represents an important step forward in population screening. The next stage is to assess the robustness and reliability of these findings by assessing performance in the third arm of the UKCTOCS trial (the multi-modal screening arm)."

(Press release, Mercy BioAnalytics, OCT 28, 2025, View Source [SID1234657081])

On October 28, 2025, Shanghai Fosun Pharmaceutical (Group) Co., Ltd. ("Fosun Pharma" or "the Group"; SSE: 600196, HKEX: 02196), a leading innovation-driven global healthcare company, reported its financial results for the first three quarters of 2025. In the first three quarters of 2025, Fosun Pharma achieved operating revenue of RMB29,393 million, net profit attributable to shareholders of RMB2,523 million. The revenue from Innovative Drugs grew steadily, exceeding RMB6,700 million in the first three quarters of 2025, up by 18.09% period-on-period, implying a continued optimization of revenue structure.

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Meanwhile, Fosun Pharma continued to deepen lean operations, drive cost reduction and efficiency enhancement, and advance asset-light strategies to optimize assets and financial structure, actively strengthen supply chain management and operational efficiency, and achieve healthy operating cash flow. In the first three quarters of 2025, the net cash flow from operating activities of Fosun Pharma amounted to RMB3,382 million, up by 13.23% period-on-period, representing a sustained improvement in operational quality.

Revenue from Innovative Products Maintains Steady Growth

Fosun Pharma’s innovative products focus on core therapeutic areas such as solid tumors, hematologic tumors, and immune-inflammatory disorders, while emphasizing core technology platforms including antibodies/ADCs, cell therapy, and small molecules, building a synergistic, open, and global innovative R&D system.

In the third quarter of 2025, several self-developed Innovative Drugs from Fosun Pharma achieved key milestones in major markets. Notably, 1 additional indication for the innovative small molecule CDK4/6 inhibitor Fovinaciclib Citrate Capsules (Chinese trade name:复妥宁), of which Fosun Pharma owns independent intellectual property rights, was approved in Chinese Mainland. The inhibitor is for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer, bringing more diverse treatment options to breast cancer patients in China.

In September 2025, the self-developed denosumab injection (project no.: HLX14), in both 60 mg/mL and 120 mg/1.7 mL presentations, was approved for launch successively in the United States and the European Union, becoming the first domestically developed denosumab to be approved overseas, covering all original indications. This provides additional therapeutic options in multiple areas related to bone loss, including osteoporosis.

In the hematology tumors field, the drug registration application of Brexucabtagene Autoleucel Injection (project code: FKC889) of Fosun Kairos was accepted by the National Medical Products Administration (NMPA) in September 2025. The declared indication for this application is for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Strengthening Original Innovation Capability, Building a High-Value Pipeline Portfolio

Fosun Pharma committed to innovation-driven sustainable growth, emphasizing the rational allocation of R&D resources and efficiency enhancement. The Group has gradually built a high-value pipeline portfolio and deployed radiopharmaceuticals, RNA, gene therapy, AI drug R&D and other cutting-edge technologies in order to facilitate the R&D process. Meanwhile, Fosun Pharma continuously strengthens its fundamental innovation capabilities and advances the deep integration of scientific and industrial innovation.

In terms of R&D investment, in the first three quarters of 2025, Fosun Pharma’s R&D investment amounted to RMB3,998 million in total, up by 2.12% period-on-period. In particular, R&D expenses amounted to RMB2,730 million. In the third quarter of 2025, R&D expenses amounted to RMB1,013 million, up by 28.81% period-on-period. The investment primarily focused on cutting-edge technology platforms such as radiopharmaceuticals and cell therapy, as well as global multicenter clinical trials of high-value pipelines, including HLX22 (recombinant humanized anti-HER2 monoclonal antibody injection) and HLX43 (PD-L1-targeted antibody-drug conjugate).

Fosun Pharma’s self-developed innovative anti-PD-1 monoclonal antibody (mAb) Han Si Zhuang (serplulimab injection) is making steady progress across multiple clinical studies. Among them, the phase 3 clinical study of Han Si Zhuang in combination with chemotherapy for the neo-/adjuvant treatment of gastric cancer has met the primary endpoint, supporting an early new drug application submission. Han Si Zhuang has become the world’s first perioperative (pre-/post-surgical) treatment regimen for gastric cancer in which an immunotherapy monotherapy replaces postoperative adjuvant chemotherapy, marking a major breakthrough in this field. In October, the U.S. bridging study of serplulimab injection in combination with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) has completed enrollment of all 200 patients, laying a solid foundation for the subsequent submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA). As the world’s first anti-PD-1 mAb approved for 1L treatment of ES-SCLC, serplulimab has been approved in nearly 40 countries and regions including China, the U.K., Germany, Singapore and India, serving as a high-quality example of Chinese innovation drugs reaching global markets.

In October 2025, HLX43 (PD-L1-targetede antibody-drug conjugate) for injection was granted Orphan-Drug Designation (ODD) by the U.S. FDA for the treatment of thymic epithelial tumors (TETs). This designation will facilitate the subsequent R&D, registration, and commercialization of the product for the relevant indication in the United States.HLX43 is a potential best-in-class (BIC) broad-spectrum anti-tumor antibody-drug conjugate (ADC) that combines dual mechanisms of action—immune checkpoint blockade and payload-mediated cytotoxicity. As the world’s first PD-L1 ADC developed for TETs, HLX43 has demonstrated promising preliminary efficacy in the later-line treatment of patients with TC.It is positioned to address the unmet clinical need for ADC therapies in this rare and highly aggressive malignancy.Currently, Fosun Pharma’s subsidiary, Henlius, is advancing the clinical development of HLX43 at full speed, with over 400 patients enrolled globally.

In September 2025, Fosun Pharma established a radiotherapy business platform, Xingrui Jingxuan, which will deploy diagnosis-therapy integrated radiopharmaceuticals development in pan-tumor through both independent R&D and collaborative pathways, bringing more benefits to patients.

Launching Share Incentive Scheme, Successfully Issuing First Medium-to-Long Term Sci-Tech Innovation Bond in Private Pharmaceutical Industry

In addition, in the first three quarters of 2025, Fosun Pharma completed its A-share and H-share repurchase plans on schedule and proposed adoption of the 2025 A share option incentive scheme and the H share restricted share unit (RSU) scheme, further strengthening its long-term incentive mechanism. In August 2025, the Group successfully issued RMB 1 billion of medium-to-long-term Sci-Tech Innovation Bonds with a maturity of two years, becoming the first private pharmaceutical company to issue such bonds after the joint announcement of the People’s Bank of China and the China Securities Regulatory Commission in May 2025 regarding support for Sci-Tech Innovation Bonds. The bonds carry a coupon rate of 2.70% and will provide strong funding support for Fosun Pharma as it deploys in key scientific innovation areas, accelerating the transformation and commercialization of innovative products.

Looking forward, Fosun Pharma will continue to adhere to innovation-driven development, optimize R&D resource allocation, accelerate the clinical progress and commercialization of high-potential pipeline, and remain committed to delivering higher-quality and more accessible healthcare products and services to patients worldwide.

(Press release, Fosun, OCT 28, 2025, View Source [SID1234661789])

On October 28, 2025 Novartis CEO Vas Narasimhan, reported on Q3 2025 results and said;

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"Novartis delivered solid financial performance in Q3, more than offsetting the impact of increasing generic erosion in the US. Our key growth drivers performed well, including Kisqali, Kesimpta, Pluvicto and Scemblix. Importantly, we achieved FDA approval for Rhapsido in CSU and positive Phase III readouts for ianalumab in Sjogren’s disease – two assets with pipeline-in-a-pill potential that could underpin our growth through 2030 and beyond. In addition, we completed several deals in the quarter to further strengthen our pipeline in core therapeutic areas. We remain well on track to achieve our guidance for 2025 and over the mid-term."

Key figures
Q3 2025 Q3 2024 % change 9M 2025 9M 2024 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 13 909 12 823 8 7 41 196 37 164 11 11
Operating income 4 501 3 627 24 27 14 028 11 014 27 31
Net income 3 930 3 185 23 25 11 563 9 119 27 29
EPS (USD) 2.04 1.58 29 31 5.94 4.50 32 35
Free cash flow 6 217 5 965 4 15 941 12 618 26
Core operating income 5 460 5 145 6 7 16 960 14 635 16 18
Core net income 4 330 4 133 5 6 13 522 11 822 14 17
Core EPS (USD) 2.25 2.06 9 10 6.94 5.83 19 21
Strategy

Our focus

Novartis is a "pure-play" innovative medicines company. We have a clear focus on four core therapeutic areas (cardiovascular-renal-metabolic, immunology, neuroscience and oncology), with multiple significant in-market and pipeline assets in each of these areas, that address high disease burden and have substantial growth potential. In addition to two established technology platforms (chemistry and biotherapeutics), three emerging platforms (gene & cell therapy, radioligand therapy and xRNA) are being prioritized for continued investment into new R&D capabilities and manufacturing scale. Geographically, we are focused on growing in our priority geographies – the US, China, Germany and Japan.

Our priorities

Accelerate growth: Renewed attention to deliver high-value medicines (NMEs) and focus on launch excellence, with a rich pipeline across our core therapeutic areas.
Deliver returns: Continuing to embed operational excellence and deliver improved financials. Novartis remains disciplined and shareholder-focused in our approach to capital allocation, with substantial cash generation and a strong capital structure supporting continued flexibility.
Strengthen foundations: Unleashing the power of our people, scaling data science and technology and continuing to build trust with society.

Financials

Third quarter

Net sales were USD 13.9 billion (+8%, +7% cc), with volume contributing 16 percentage points to growth. Generic competition had a negative impact of 7 percentage points, driven by Promacta, Tasigna and Entresto generics in the US. Pricing had a negative impact of 2 percentage points, driven by revenue deduction adjustments mainly in the US. Currency had a positive impact of 1 percentage point.

Operating income was USD 4.5 billion (+24%, +27% cc), mainly driven by higher net sales and lower impairments, partly offset by higher R&D investments.

Net income was USD 3.9 billion (+23%, +25% cc), mainly driven by higher operating income. EPS was USD 2.04 (+29%, +31% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 5.5 billion (+6%, +7% cc), mainly driven by higher net sales, partly offset by higher R&D investments. Core operating income margin was 39.3% of net sales (-0.8 percentage points, stable in cc).

Core net income was USD 4.3 billion (+5%, +6% cc), mainly due to higher core operating income, partly offset by other core financial income and expense. Core EPS was USD 2.25 (+9%, +10% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow amounted to USD 6.2 billion (+4% USD), compared with USD 6.0 billion in the prior-year quarter, driven by higher net cash flows from operating activities.

Nine months

Net sales were USD 41.2 billion (+11%, +11% cc), with volume contributing 14 percentage points to growth. Generic competition had a negative impact of 3 percentage points, while pricing and currency had no impact.

Operating income was USD 14.0 billion (+27%, +31% cc), mainly driven by higher net sales and lower impairments, partly offset by higher investments behind priority brands and launches.

Net income was USD 11.6 billion (+27%, +29% cc), mainly driven by higher operating income. EPS was USD 5.94 (+32%, +35% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 17.0 billion (+16%, +18% cc), mainly driven by higher net sales, partly offset by higher investments behind priority brands and launches. Core operating income margin was 41.2% of net sales, increasing 1.8 percentage points (2.5 percentage points cc).

Core net income was USD 13.5 billion (+14%, +17% cc), mainly due to higher core operating income. Core EPS was USD 6.94 (+19%, +21% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow amounted to USD 15.9 billion (+26% USD), compared with USD 12.6 billion in the prior-year period, driven by higher net cash flows from operating activities.

Q3 priority brands

Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q3 growth) including:

Kisqali (USD 1 329 million, +68% cc) sales grew strongly across all regions, including +91% growth in the US with strong momentum from the recently launched early breast cancer indication as well as continued share gains in metastatic breast cancer.
Kesimpta (USD 1 222 million, +44% cc) sales grew across all regions driven by increased demand and strong access.
Pluvicto (USD 564 million, +45% cc) showed sustained demand growth in the US following the pre-taxane metastatic castration-resistant prostate cancer (mCRPC) approval, as well as continued access expansion ex-US in the post-taxane mCRPC setting, with 25 countries now approved including Japan.
Scemblix (USD 358 million, +95% cc) sales grew across all regions, demonstrating the continued high unmet need in CML, with strong momentum from the early-line indication in the US and Japan.
Leqvio (USD 308 million, +54% cc) continued steady growth across all regions, with a focus on increasing account and patient adoption, and continuing medical education.
Fabhalta (USD 149 million, +236% cc) sales grew, reflecting market share gains in PNH globally and continued launch progress in IgAN and C3G in the US.
Lutathera (USD 213 million, +11% cc) sales grew mainly in the US, Japan and Europe due to increased demand and earlier-line adoption.
Cosentyx (USD 1 698 million, -1% cc) sales were broadly stable, as strong volume growth in the US was partially offset by higher revenue deductions, and ex-US declined due to a one-time price effect in the prior year. Novartis remains confident in Cosentyx USD 8 billion+ peak sales guidance.
Zolgensma (USD 301 million, -5% cc) sales declined reflecting a lower incidence of SMA compared to prior year.

Net sales of the top 20 brands in the third quarter and nine months

Q3 2025 % change 9M 2025 % change
USD m USD cc USD m USD cc
Entresto 1 877 1 -1 6 495 15 15
Cosentyx
– excl. revenue deduction adjust.* 1 698

0
5 -1
4 4 861

7
9 7
9
Kisqali 1 329 69 68 3 462 62 63
Kesimpta 1 222 46 44 3 198 41 40
Tafinlar + Mekinist 550 3 1 1 675 9 9
Jakavi 539 8 4 1 555 7 6
Promacta/Revolade 362 -36 -38 1 410 -14 -14
Pluvicto 564 46 45 1 389 33 33
Ilaris 473 27 26 1 369 25 24
Xolair 440 5 3 1 339 8 8
Tasigna 221 -47 -48 925 -27 -26
Zolgensma 301 -2 -5 925 -3 -4
SandostatinGroup 302 -1 -1 922 -5 -5
Scemblix 358 97 95 894 85 84
Leqvio 308 56 54 863 63 61
Lutathera 213 12 11 613 15 14
ExforgeGroup 176 1 0 546 0 2
Lucentis 148 -40 -42 510 -39 -39
DiovanGroup 143 -5 -5 447 -1 0
GalvusGroup 126 -21 -20 373 -19 -16
Top 20 brands total 11 350 10 9 33 771 14 14
*Sales growth impacted by a one-time revenue deduction adjustment in the US

R&D update – key developments from the third quarter

New approvals

Rhapsido
(remibrutinib) Rhapsido was approved by the FDA as an oral treatment for adult patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment. It is the first FDA-approved Bruton’s tyrosine kinase inhibitor (BTKi) for CSU. Remibrutinib is also in Phase III development for chronic inducible urticaria, hidradenitis suppurativa and food allergy, as well as multiple sclerosis and myasthenia gravis.
Regulatory updates

Scemblix (asciminib) The CHMP of the EMA adopted a positive opinion and recommended granting marketing authorization for Scemblix for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) in all lines of treatment.

Results from ongoing trials and other highlights

Ianalumab
(VAY736) The Phase III NEPTUNUS-1 and -2 trials evaluating ianalumab in adults with active Sjögren’s disease met their primary endpoint, showing statistically significant improvements in disease activity as measured by a reduction in ESSDAI compared to placebo. Ianalumab was well tolerated and demonstrated a favorable safety profile, supporting its potential to become the first targeted treatment for this chronic autoimmune disease. Novartis plans to submit ianalumab to health authorities globally and was granted Fast Track Designation by the FDA.

In the Phase III VAYHIT2 trial, ianalumab plus eltrombopag significantly extended the time to treatment failure compared to placebo plus eltrombopag in adult patients with primary immune thrombocytopenia (ITP), previously treated with corticosteroids. The safety profile was consistent with previous studies. Data will be presented at an upcoming medical meeting and included in regulatory submissions in 2027.

Ianalumab is also in Phase III development for systemic lupus erythematosus, lupus nephritis and warm autoimmune hemolytic anemia.
Pluvicto
(lutetium Lu177
vipivotide
tetraxetan) In the Phase III PSMAddition trial, Pluvicto plus standard-of-care (SoC) reduced risk of progression or death by 28% versus SoC alone, with a positive trend in overall survival in patients with PSMA+ metastatic hormone-sensitive prostate cancer (mHSPC). Safety remained consistent with PSMAfore and VISION trials. Data presented at ESMO (Free ESMO Whitepaper).
Kisqali
(ribociclib) The five-year analysis of the pivotal Phase III NATALEE trial in the broadest population of high-risk stage II and III HR+/HER2- early breast cancer (eBC) showed the addition of Kisqali to endocrine therapy (ET) reduced the risk of recurrence by 28.4% compared to ET alone. Data also showed a 29.1% risk reduction in distant disease-free survival, a positive trend in overall survival, and no new safety signals. Data presented at ESMO (Free ESMO Whitepaper).
Cosentyx
(secukinumab) The Phase III REPLENISH study met its primary endpoint, with Cosentyx demonstrating statistically significant and clinically meaningful sustained remission compared to placebo at week 52 in adults with relapsing polymyalgia rheumatica (PMR). Full data will be presented at an upcoming medical congress and submitted to health authorities in 2026.
Fabhalta
(iptacopan) In the Phase III APPLAUSE-IgAN final analysis, Fabhalta demonstrated statistically significant, clinically meaningful superiority compared to placebo in slowing IgAN progression measured by annualized total slope of estimated glomerular filtration rate (eGFR) decline over two years. Full data will be presented at future medical meetings and included in regulatory submissions in 2026.
Leqvio
(Inclisiran) In the Phase IV V-DIFFERENCE study, 85% of patients with hypercholesterolemia who had not reached guideline-recommended LDL-C targets despite optimized lipid-lowering therapy (LLT) achieved their goals with Leqvio plus LLT, versus 31% with placebo plus LLT, with benefits evident in as early as 30 days. Leqvio also reduced LDL-C by 59% over 360 days, outperforming placebo plus LLT by 35%. Data presented at ESC.
Entresto
(sacubitril/ valsartan) Data from the Phase IV PARACHUTE-HF study in patients with heart failure with reduced ejection fraction due to chronic Chagas disease showed that Entresto outperformed enalapril on a composite endpoint of cardiovascular death, heart failure hospitalization or NT-proBNP change. Entresto was well tolerated, with no new safety signals identified. Data presented at ESC.
Kesimpta
(ofatumumab) In the ARTIOS Phase IIIb study, patients with RMS who switched to Kesimpta after breakthrough disease on fingolimod or fumarate-based therapies showed a substantial reduction in disease activity. This was reflected in a low annualized relapse rate (ARR of 0.06 over 96 weeks), near-complete suppression of MRI activity, and over 90% of participants achieving no evidence of disease activity (NEDA-3). No new safety concerns were identified, regardless of prior disease-modifying treatment.

In the separate ALITHIOS open-label extension study, more than 90% of naïve patients receiving Kesimpta showed no evidence of disease activity (NEDA-3) at 7 years, with no new safety concerns, reinforcing the benefit of introducing Kesimpta early. Data from both studies presented at ECTRIMS.
Selected transactions Novartis entered into an agreement to acquire Tourmaline Bio, a clinical-stage biopharmaceutical company developing pacibekitug, a Phase III-ready anti-IL-6 monoclonal antibody for atherosclerotic cardiovascular disease (ASCVD). In Phase II, pacibekitug reduced median high-sensitivity C-reactive protein (hsCRP) levels by up to 86% compared to placebo, with similar incidence rates of adverse events and serious adverse events. The transaction is expected to close on October 28, 2025.

Novartis entered a second collaboration with Monte Rosa Therapeutics, in addition to the existing license agreement for VAV1 degraders, announced in October 2024. Under the new agreement, Novartis receives an exclusive license to an undisclosed discovery target and options to license two programs from Monte Rosa’s preclinical immunology portfolio.

Novartis continued its collaboration with Argo Biopharma, adding two new agreements: an exclusive license to an siRNA candidate currently in IND-enabling studies and expected to enter Phase I in 2026, and an option to exclusively license two second-generation siRNA molecules currently in development, with a right of first negotiation to the Phase II ANGPTL3 program.

Novartis entered into a global licensing and collaboration agreement with Arrowhead Pharmaceuticals for ARO-SNCA, a preclinical-stage siRNA therapy targeting alpha-synuclein for the treatment of synucleinopathies such as Parkinson’s disease. The agreement also includes additional collaboration targets leveraging Arrowhead’s proprietary Targeted RNAi Molecule (TRiM) platform.
Capital structure and net debt

Retaining a good balance between investment in the business, a strong capital structure, and attractive shareholder returns remains a priority.

During the first nine months of 2025, Novartis repurchased a total of 66.4 million shares for USD 7.5 billion on the SIX Swiss Exchange second trading line. These repurchases included 49.1 million shares (USD 5.4 billion) under the USD 15 billion share buyback (announced in July 2023 and completed in July 2025) and 6.6 million shares (USD 0.8 billion) under the new up-to USD 10 billion share buyback announced in July 2025. In addition, 10.7 million shares (USD 1.3 billion) were repurchased to mitigate anticipated full-year dilution related to the equity-based compensation plans of associates. Further, 1.6 million shares (equity value of USD 0.2 billion) were repurchased from associates. In the same period, 11.7 million shares (equity value of USD 0.9 billion) were delivered to associates related to equity-based compensation plans. Consequently, the total number of shares outstanding decreased by 56.3 million versus December 31, 2024. These treasury share transactions resulted in an equity decrease of USD 6.8 billion and a net cash outflow of USD 7.7 billion.

Net debt increased to USD 20.4 billion at September 30, 2025, compared to USD 16.1 billion at December 31, 2024. The increase was mainly due to the free cash flow of USD 15.9 billion being more than offset by the USD 7.8 billion annual dividend payment, cash outflows for treasury share transactions of USD 7.7 billion and net cash outflow for M&A, intangible assets transactions and other acquisitions of USD 3.7 billion.

As of Q3 2025, the long-term credit rating for the company is Aa3 with Moody’s Ratings and AA- with S&P Global Ratings.

2025 outlook

Barring unforeseen events; growth vs. prior year in cc
Net sales Expected to grow high single-digit
Core operating income Expected to grow low-teens
Foreign exchange impact

If late-October exchange rates prevail for the remainder of 2025, the foreign exchange impact for the year would be neutral to positive 1 percentage point on net sales and negative 2 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.

Key figures1

Q3 2025 Q3 2024 % change 9M 2025 9M 2024 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 13 909 12 823 8 7 41 196 37 164 11 11
Operating income 4 501 3 627 24 27 14 028 11 014 27 31
As a % of sales 32.4 28.3 34.1 29.6
Net income 3 930 3 185 23 25 11 563 9 119 27 29
EPS (USD) 2.04 1.58 29 31 5.94 4.50 32 35
Net cash flows from
operating activities 6 571 6 286 5 16 880 13 426 26
Non-IFRS measures
Free cash flow 6 217 5 965 4 15 941 12 618 26
Core operating income 5 460 5 145 6 7 16 960 14 635 16 18
As a % of sales 39.3 40.1 41.2 39.4
Core net income 4 330 4 133 5 6 13 522 11 822 14 17
Core EPS (USD) 2.25 2.06 9 10 6.94 5.83 19 21

(Press release, Novartis, OCT 28, 2025, View Source [SID1234657040])

On October 28, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators presented positive preclinical data for Reqorsa Gene Therapy (quaratusugene ozeplasmid) for the treatment of ALK-EML4 positive (ALK+) non-small cell lung cancer (NSCLC).

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The data were presented at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), which took place October 22-26, 2025 at the Hynes Convention Center in Boston.

"The preclinical data presented at AACR (Free AACR Whitepaper)-NCI-EORTC reinforces our oncology program strategy that reintroduces tumor suppressor genes to target cancer cells," said Ryan Confer, President and Chief Executive Officer at Genprex. "These data also add to the existing preclinical data showing that REQORSA has significant activity on its own as well as when combined with other therapies in a mouse xenograft model with ALK-EML4 rearrangement. The combination of REQORSA and an ALK inhibitor led to longer survival in the mouse model. ALK-EML4 rearrangements occur in approximately 4% of all patients with NSCLC. We believe these positive data open a pathway for a potential future clinical trial in ALK-positive lung cancer."

The featured Genprex-supported poster presented at the 2025 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics:

Title: "Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing non-small cell lung carcinoma induces apoptosis and is highly effective in preclinical studies"

Collaborator: The University of Michigan Rogel Cancer Center

Session: Poster Session C

Session Date and Time: Saturday, October 25, 2025 from 12:30 – 4:00 p.m. ET

In the study researchers demonstrated that REQORSA can overexpress the tumor suppressor gene, TUSC2, in EML4-ALK+ NSCLC cell lines and patient derived organoids (PDOs). The upregulation of TUSC2 by REQORSA therapy induced apoptosis in ALK+ NSCLC cells, including those resistant to alectinib. Researchers also demonstrated that combining REQORSA with alectinib further increases apoptosis. Using in vivo mouse experiments with xenografts of a human ALK+-EML4 NSCLC cell line, treatment with REQORSA and alectinib together improved survival when compared to control. These experiments provide support for a trial of REQORSA in patients with ALK+-EML4 NSCLC.

This poster has been made available on Genprex’s website here.

About Reqorsa Gene Therapy

REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.

(Press release, Genprex, OCT 28, 2025, View Source [SID1234657066])