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European Commission Grants Conditional Approval of EZMEKLY® (mirdametinib) for the Treatment of Adult and Pediatric Patients with NF1-PN

On July 18, 2025 SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany, reported that the European Commission (EC) granted conditional marketing authorization for EZMEKLY (mirdametinib) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above (Press release, SpringWorks Therapeutics, JUL 18, 2025, View Source [SID1234654439]). EZMEKLY is the first and only therapy approved in the European Union (EU) for both adults and children with NF1-PN.

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"Patients with NF1-PN often face physical and mental health challenges and impaired quality of life given the limited treatment options available for this lifelong and debilitating disease," said Ignacio Blanco, MD, PhD, Chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol, Spain. "This approval represents an important advance, especially for adults who previously did not have an approved treatment. In clinical trials, EZMEKLY demonstrated an encouraging efficacy and safety profile in both adults and children, and importantly, is available in a tablet that dissolves easily in water for people who are unable to swallow a pill and could therefore not previously receive therapy."

"This European Commission approval is an important milestone for NF patients and caregivers, as it means more treatment options for patients with plexiform neurofibromas, including adults," said Annette Bakker, PhD, Chief Executive Officer of the Children’s Tumor Foundation (CTF) and Dariusz Adamczewski, MD, Director CTF Europe. "This is the kind of progress that happens when researchers, industry and organizations like ours work together with a shared focus on delivering new treatments for patients."

NF1 is a genetic disorder that affects approximately 3 in 10,000 people in the EU, or an estimated 135,000 people.1,2 Among patients with NF1, the lifetime risk of developing plexiform neurofibromas is approximately 30% to 50%. These tumors grow in an infiltrative pattern along the peripheral nerve sheath and can cause severe disfigurement, pain and functional impairment.3,4 Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.5 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8

"Bringing innovation to patients living with rare tumors around the world is a clear reflection of our focus on addressing significant unmet needs and transforming outcomes for patients and their families," said Jan Kirsten, Global Head of Rare Tumor Business. "With the European approval of EZMEKLY, the first therapy approved for both adults and children with NF1-PN, we are taking a major step toward improving care for this underserved community and are committed to making our medicine available to eligible NF1-PN patients across Europe as quickly as possible."

The EC approval of EZMEKLY is based on results from the ongoing, multi-center, open-label, single arm Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN age 2 years or older (58 adults and 56 pediatric patients). The study met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating an ORR of 41% (N= 24/58) in adults and 52% in children (N=29/56). The median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children. Among those with a confirmed response, 88% percent of adults and 90% of children had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration. Both adults and children also experienced early and sustained significant improvements from baseline in pain and quality of life as assessed across multiple patient-reported outcome tools.9

EZMEKLY demonstrated a manageable safety and tolerability profile. The most common adverse reactions reported in adults receiving EZMEKLY were dermatitis acneiform (83%), diarrhea (55%), nausea (55%), blood creatine phosphokinase increased (47%), musculoskeletal pain (41%), vomiting (37%) and fatigue (36%). The most common adverse reactions occurring in children were blood creatine phosphokinase increased (59%), diarrhea (53%), dermatitis acneiform (43%), musculoskeletal pain (41%), abdominal pain (40%), vomiting (40%), and headache (36%).9

EZMEKLY is available in 1 and 2 mg capsules and in a 1 mg dispersible tablet, which dissolves easily in water.

About the ReNeu Trial

ReNeu (NCT03962543) is an ongoing, multi-center, open-label, single arm, Phase 2b trial evaluating the efficacy, safety and tolerability of mirdametinib in patients ≥2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate (ORR) defined as the proportion of patients with a ≥20% reduction in target tumor volume on consecutive scans during the 24-cycle treatment phase, as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability, duration of response, and changes in patient-reported outcomes from baseline to Cycle 13. The treatment phase of the trial is complete, and results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow-up portion of the study, which is ongoing.

About NF1-PN

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.10,11 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals.3,12 In the EU, NF1 affects approximately 3 in 10,000 people, or an estimated 135,000 people.1,2 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.13 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.1

Patients with NF have approximately a 30% to 50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.3,4,5 NF1-PNs are most often diagnosed in the first two decades of life.3 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.14,15

Surgical removal of these tumors can be challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.5 Up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8

About GOMEKLI/ EZMEKLY (mirdametinib)

GOMEKLI (mirdametinib) is an oral, small molecule MEK inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

Mirdametinib is marketed under the brand name EZMEKLY in the European Union and is conditionally approved by the European Commission (EC) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above.

The FDA and the EC have granted Orphan Drug designation for mirdametinib for the treatment of NF1.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Ocular Toxicity: GOMEKLI can cause ocular toxicity including retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), and blurred vision. In the adult pooled safety population, ocular toxicity occurred in 28% of patients treated with GOMEKLI: 21% were Grade 1, 5% were Grade 2 and 1.3% were Grade 3. RVO occurred in 2.7%, RPED occurred in 1.3%, and blurred vision occurred in 9% of adult patients. In the pediatric pooled safety population, ocular toxicity occurred in 19% of patients: 17% were Grade 1 and 1.7% were Grade 2. Conduct comprehensive ophthalmic assessments prior to initiating GOMEKLI, at regular intervals during treatment, and to evaluate any new or worsening visual changes such as blurred vision. Continue, withhold, reduce the dose, or permanently discontinue GOMEKLI as clinically indicated.

Left Ventricular Dysfunction: GOMEKLI can cause left ventricular dysfunction. GOMEKLI has not been studied in patients with a history of clinically significant cardiac disease or LVEF <55% prior to initiation of treatment. In the ReNeu study, decreased LVEF of 10 to <20% occurred in 16% of adult patients treated with GOMEKLI. Five patients (9%) required dose interruption, one patient (1.7%) required a dose reduction, and one patient required permanent discontinuation of GOMEKLI. The median time to first onset of decreased LVEF in adult patients was 70 days. Decreased LVEF of 10 to <20% occurred in 25%, and decreased LVEF of ≥20% occurred in 1.8% of pediatric patients treated with GOMEKLI. One patient (1.8%) required dose interruption of GOMEKLI. The median time to first onset of decreased LVEF in pediatric patients was 132 days. All patients with decreased LVEF were identified during routine echocardiography, and decreased LVEF resolved in 75% of patients. Before initiating GOMEKLI, assess ejection fraction (EF) by echocardiogram. Monitor EF every 3 months during the first year and then as clinically indicated. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.

Dermatologic Adverse Reactions: GOMEKLI can cause dermatologic adverse reactions including rash. The most frequent rashes included dermatitis acneiform, rash, eczema, maculo-papular rash and pustular rash. In the pooled adult safety population, rash occurred in 92% of patients treated with GOMEKLI and required permanent discontinuation in 11% of adult patients. In the pooled pediatric safety population, rash occurred in 72% of patients treated with GOMEKLI and resulted in permanent discontinuation of GOMEKLI in 3.4% of patients. Initiate supportive care at first signs of dermatologic adverse reactions. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.

Embryo-Fetal Toxicity: GOMEKLI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of GOMEKLI. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Also advise patients to use effective contraception during treatment with GOMEKLI and for 6 weeks after the last dose (females) or 3 months after the last dose (males).

ADVERSE REACTIONS

The most common adverse reactions (>25%) in adult patients were rash (90%), diarrhea (59%), nausea (52%), musculoskeletal pain (41%), vomiting (38%), and fatigue (29%). Serious adverse reactions occurred in 17% of adult patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase.
The most common adverse reactions (>25%) in pediatric patients were rash (73%), diarrhea (55%), musculoskeletal pain (41%), abdominal pain (39%), vomiting (39%), headache (34%), paronychia (32%), left ventricular dysfunction (27%), and nausea (27%). Serious adverse reactions occurred in 14% of pediatric patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase.

USE IN SPECIFIC POPULATIONS

Pregnancy & Lactation. Verify the pregnancy status of patients of reproductive potential prior to initiating GOMEKLI. Due to the potential for adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with GOMEKLI and for 1 week after the last dose.
You are encouraged to report negative side effects of prescription drugs to the FDA. To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Sanofi completes acquisition of Blueprint Medicines

On July 18, 2025 Sanofi reported the completion of its acquisition of Blueprint Medicines Corporation (Blueprint), adding to its portfolio a commercialized medicine, a promising pipeline, and the expertise of a company specializing in systemic mastocytosis (SM), a rare immunological disease, and other KIT-driven diseases (Press release, Sanofi, JUL 18, 2025, View Source [SID1234654438]).

In addition, the acquisition of Blueprint brings Sanofi an established presence among allergists, dermatologists, and immunologists which is expected to enhance Sanofi’s ability to advance its growing immunology pipeline.

The acquisition includes a rare immunology disease medicine, Ayvakit/Ayvakyt (avapritinib), approved in the US and EU. Ayvakit/Ayvakyt is the only approved medicine for advanced and indolent systemic mastocytosis (ASM & ISM), which is characterized by the accumulation and activation of aberrant mast cells in bone marrow, skin, the gastrointestinal tract, and other organs.

The acquisition also includes elenestinib, a next-generation medicine for SM that is a potent and highly selective KIT D816V inhibitor with limited central nervous system penetration. The oral investigational ISM medication is the subject of HARBOR, a phase 2/3 study (clinical study identifier: NCT04910685). The ongoing, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of elenestinib plus symptom-directed therapy in patients with ISM and smoldering SM.

Sanofi also acquired BLU-808, an investigational oral, highly potent and selective wild-type KIT inhibitor. Wild-type KIT plays a central role in mast cell activation, which is implicated in a broad range of inflammatory diseases.

The tender offer for all outstanding shares of Blueprint common stock, par value $0.001 per share expired at 17:00 EDST, on Thursday, July 17, 2025. The minimum tender condition and all of the other conditions to the offer have been satisfied, and on July 17, 2025, Sanofi accepted for payment and will promptly pay for all shares validly tendered and not validly withdrawn.

Following its acceptance of the tendered shares, Sanofi completed its acquisition of Blueprint through the merger of a wholly owned subsidiary of Sanofi with and into Blueprint, pursuant to Section 251(h) of the General Corporation Law of the State of Delaware, with Blueprint continuing as the surviving corporation, and becoming an indirect, wholly owned subsidiary of Sanofi. Sanofi is financing the transaction with a combination of cash on hand and proceeds from commercial paper issuances and the acquisition will not have a significant impact on Sanofi’s financial guidance for 2025. It is immediately accretive to gross margin and accretive to business operating income and EPS after 2026.

In connection with the merger, all Blueprint shares not validly tendered in the tender offer have been converted into the right to receive $129.00 per share in cash, without interest and subject to any withholding of taxes required by applicable legal requirements, plus one non-transferable contractual contingent right per share, representing the right to receive contingent payments of up to an aggregate amount of $6.00 per share in cash, without interest, upon the achievement of specified milestones on or prior to the expiration of the applicable milestone period.

As of July 18, 2025, Blueprint common stock will cease to be traded on the NASDAQ Global Select Stock Market.

About Ayvakit

Ayvakit (avapritinib) is the first and only medicine approved by the US Food and Drug Administration (FDA) to treat the root cause of SM. It was FDA approved for the treatment of advanced SM in June 2021 and indolent SM in May 2023. It now is indicated in adults with ISM, adults with advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. The medicine is approved in the EU as Ayvakyt for the treatment of adults with ISM with moderate to severe symptoms inadequately controlled on symptomatic treatment, adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Globally, the medicine is approved for one or more indications in 16 countries, including China where it is marketed by CStone Pharmaceuticals, paying tiered percentage royalties on sales.

Bristol Myers Squibb Announces Topline Results from Phase 3 INDEPENDENCE Trial for Reblozyl® (luspatercept-aamt) in Adult Patients with Myelofibrosis-Associated Anemia

On July 18, 2025 Bristol Myers Squibb (NYSE: BMY) reported the Phase 3 INDEPENDENCE trial evaluating Reblozyl (luspatercept-aamt) with concomitant janus kinase inhibitor (JAKi) therapy in adult patients with myelofibrosis-associated anemia receiving red blood cell (RBC) transfusions did not meet its primary endpoint of RBC transfusion independence during any consecutive 12-week period, starting within the first 24 weeks of treatment, compared to placebo (p=0.0674) (Press release, Bristol-Myers Squibb, JUL 18, 2025, View Source [SID1234654437]). Patients saw a numerical and clinically meaningful improvement in RBC transfusion independence favoring Reblozyl, in line with previous results from the Phase 2 trial (NCT03194542).

Several important secondary measures also showed a clinically meaningful benefit favoring Reblozyl, which included a higher number of patients who achieved at least a 50% reduction (and by at least 4 RBC units) in RBC transfusion burden, as well as a higher number of patients achieving a hemoglobin (Hb) level increase by at least 1 g/dL while remaining transfusion independent for at least 12 consecutive weeks.

Frequently observed treatment emergent adverse events were consistent with the known safety profile of Reblozyl previously reported across indications.

The company is encouraged by the clinically meaningful results of the study and will engage with the FDA and EMA to discuss the submission of marketing applications.

"It is promising to see that Reblozyl led to clinically relevant improvement of anemia for patients with myelofibrosis, where patients often become increasingly transfusion dependent over time," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology, and Cell Therapy for Bristol Myers Squibb. "We remain confident in the ability of Reblozyl to improve outcomes for patients with myelofibrosis-associated anemia and believe the totality of these results, including meaningful improvements in transfusion burden and hemoglobin levels, support the potential to address an unmet need in patients who have few treatment options."

"Anemia remains a significant challenge in the treatment of myelofibrosis, with many patients still dependent on red blood cell transfusions or suboptimal treatment approaches that can sometimes worsen anemia associated with the disease," said John Mascarenhas, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at The Tisch Cancer Institute. "Patients with myelofibrosis and anemia are difficult to treat, and these results show that Reblozyl can have an important impact on anemia associated with the disease."

Reblozyl is a standard of care for the first-line treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require RBC transfusions, treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and treatment of anemia in adult patients with beta thalassemia who require RBC transfusions.

Bristol Myers Squibb thanks the patients, investigators and clinical trial sites who participated in the INDEPENDENCE clinical trial.

About the Phase 3 INDEPENDENCE Trial
INDEPENDENCE (NCT04717414) is a Phase 3, double-blind, randomized study to compare the efficacy and safety of luspatercept vs placebo in patients with myeloproliferative neoplasms (MPN)-associated myelofibrosis (MF) on associated JAK2 inhibitor therapy and who require red blood cell (RBC) transfusions. The primary outcome measure is the proportion of patients who became RBC-transfusion-free over any consecutive 12-week period starting within the first 24 weeks. The key secondary endpoint was the proportion of patients who became RBC transfusion independent over any consecutive 16-week period, starting within the first 24 weeks. Additional secondary endpoints measured increase in hemoglobin (Hb) levels, and at least a 50% reduction in RBC transfusion burden.

About Myelofibrosis
Myelofibrosis (MF) is a rare type of blood cancer, with an annual incidence of approximately 0.3 cases per 100,000 individuals in the U.S. It is one of a group of blood cancers called chronic myeloproliferative neoplasms (MPN), in which bone marrow stem cells that produce blood cells develop and function abnormally. MF is characterized by the buildup of scar tissue, called fibrosis, in the bone marrow. As scar tissue increases, the bone marrow cannot make enough healthy blood cells, which can lead to anemia, a condition characterized by not having enough healthy red blood cells to carry oxygen to the body’s tissues.

About Reblozyl
Reblozyl, a first-in-class therapeutic option, promotes late-stage red blood cell maturation in animal models. Reblozyl is being developed and commercialized through a global collaboration with Merck as of November 2021. Reblozyl is indicated in the U.S. for the treatment of:

anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions, and
anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.
anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndrome with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. In the U.S., Reblozyl is not indicated for use in patients with non-transfusion-dependent beta thalassemia.

Important Safety Information

WARNINGS AND PRECAUTIONS

Thrombosis/Thromboembolism
In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.

Hypertension
Hypertension was reported in 11.4% (63/554) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 2% to 9.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In ESA-refractory or -intolerant adult patients with MDS with normal baseline blood pressure, 26 (30%) patients developed SBP ≥130 mm Hg and 23 (16%) patients developed DBP ≥80 mm Hg. In ESA-naïve adult patients with MDS with normal baseline blood pressure, 23 (36%) patients developed SBP ≥140 mm Hg and 11 (6%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Extramedullary Hematopoietic (EMH) Masses
In adult patients with transfusion-dependent beta thalassemia, EMH masses were observed in 3.2% of REBLOZYL-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and REBLOZYL long-term follow-up study).

In a study of adult patients with non-transfusion-dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of REBLOZYL-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. REBLOZYL is not indicated for use in patients with non-transfusion-dependent beta thalassemia.

Risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with REBLOZYL in case of serious complications due to EMH masses. Avoid use of REBLOZYL in patients requiring treatment to control the growth of EMH masses.

Embryo-Fetal Toxicity
REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.

ADVERSE REACTIONS

Beta-Thalassemia
Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML).

Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).

ESA-naïve adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included hypertension and dyspnea.

The most common (≥10%) all-grade adverse reactions included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.

ESA-refractory or -intolerant adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients.

The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection.

LACTATION
It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.

DRUG ABUSE POTENTIAL
Abuse: Abuse of REBLOZYL may be seen in athletes for the effects on erythropoiesis. Misuse of drugs that increase erythropoiesis, such as REBLOZYL, by healthy persons may lead to polycythemia, which may be associated with life-threatening cardiovascular complications.

Please see accompanying U.S. Full Prescribing Information for REBLOZYL.

Initiation of Phase 1b/2 AZALOX clinical trial of amsulostat in second blood cancer indication

On July 17, 2025 Syntara Limited (ASX:SNT), a clinical-stage drug development company, reported initiation of AZALOX, a Phase 1b/2 multi-centre study evaluating amsulostat (SNT-5505) in combination with 5-Azacitidine for the treatment of high-risk Myelodysplastic Neoplasms (MDS) and Chronic Myelomonocytic Leukemia (CMML) (Press release, Syntara, JUL 17, 2025, View Source;v=4a466cc3f899e00730cfbfcd5ab8940c41f474b6 [SID1234654426]).

The study commenced at University Medicine Mannheim (UMM), Germany, the first of nine planned centres expected to enrol patients under the German MDS Study Group. Led by Professor Susanne Saußele and her team, the trial will focus on patients with significant disease severity who are transfusion dependent.

The initial Phase 1b portion of the AZALOX trial will determine the safety profile and recommended dose of amsulostat alongside 5-Azacitidine. The Phase 2 component will then further evaluate safety and efficacy of the selected dose across 30 patients.

Patients eligible for the trial include those with confirmed high-risk MDS or CMML, who are either treatment-naïve or have undergone limited prior treatment with hypomethylating agents.

The trial is financially supported by German Cancer Aid (Deutsche Krebshilfe, DKH), with Heidelberg University sponsoring the study in collaboration with the Coordination Centre for Clinical Studies (KKS) Heidelberg.

Professor Saußele commented: "Our preclinical data suggest that with this combination therapy, we can reactivate the production of red blood cells. With this, we aim to eliminate the need for blood transfusions in the long term and reduce the risk of transformation to acute myeloid leukemia."

Syntara CEO, Gary Phillips stated: "We are delighted to be working with the German MDS Study Group as they initiate the AZALOX study. This represents an important milestone for amsulostat, leveraging the positive results in myelofibrosis and expanding to a second blood cancer indication. The AZALOX trial builds on promising preclinical data, potentially providing a new treatment option for patients suffering from MDS and CMML."

Novartis Second Quarter and Half Year 2025 financial results

On July 17, 2025 Novartis reported Second Quarter and Half Year 2025 financial results (Presentation, Novartis, JUL 17, 2025, View Source [SID1234654547]).