G-CSF

Pictured: Illustration of antibodies attacking a nerve/iStock, peterschreiber.media A small study of 15 patients published Thursday in The New England Journal of Medicine provides strong evidence of the therapeutic potential of CD19 CAR-T therapies in autoimmune disorders. The study, conducted in Germany, enrolled patients who had been diagnosed with systemic lupus erythematosus (SLE), idiopathic inflammatory myositis or systemic sclerosis. Study participants had severe and progressive disease and were resistant to at least two different immunomodulating agents. CAR-T therapies were offered through an expanded access program in Germany, meant for critically ill patients. After a median follow-up of 15 months, all eight SLE patients achieved disease remission based on the Definition of Remission in SEL tool, a unified criteria to evaluate remission in SLE patients which factors in other indices and the need for treatments. All four systemic sclerosis patients also saw reduced scores in the European Scleroderma Trials and Research Group activity index, indicating lower disease activity. In addition, all three patients with idiopathic inflammatory myositis demonstrated major clinical response, as evaluated by the American College of Rheumatology–European League against Rheumatism scale. All patients ultimately were able to stop immunosuppressive treatment. In terms of safety, 11 patients developed cytokine release syndrome, 10 of which were grade 1 while one was categorized as grade 2. One patient also developed grade 4 neutropenia, which was resolved after stopping sertraline, pregabalin and doxazosin treatment and following an injection of granulocyte colony-stimulating factor. “The dynamics of CAR T-cell expansion and of B-cell ablation were highly consistent among patients” despite having different diseases and prior treatment exposures, the researchers wrote in their paper, noting that the side effects were also “minimal” with no “prolonged bone marrow toxic effects.” “Given that patients had full B-cell reconstitution for up to two years without having relapses, it seems that a single injection of CD19 CAR T-cell therapy can lead to a long-lasting remission,” the researchers added. CAR-T therapies make use of a patient’s own T cells—which have been genetically altered in a lab to express a specific receptor—to seek out a target. This approach has worked well for cancer as the FDA has approved six CAR-T therapies, which are extremely effective for specific leukemias and lymphomas. In Thursday’s NEJM study, the researchers designed the CAR-T therapies to target CD19, a key surface protein found on B cells, which are what typically drive autoimmune diseases. While harnessing CAR-T therapies for autoimmune diseases is a relatively new strategy, a handful of companies have already started working on this approach. These include Bristol Myers Squibb, which is developing its CD19 NEX-T program in SLE and multiple sclerosis, both of which are currently in Phase I. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

LEXINGTON, Mass., Jan. 17, 2024 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced today the publication of a comprehensive review by Mora et al. in the International Journal of Cancer which summarizes the efficacy and safety of anti-GD2 monoclonal antibodies (mAbs) (dinutuximab, dinutuximab beta, and naxitamab) in children with high-risk neuroblastoma when given in combination with Leukine (sargramostim; glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]), recombinant human granulocyte colony-stimulating factor (G-CSF) or no cytokine.1 Continue Reading The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs. It also describes why the authors believe it is suboptimal to replace with Leukine with G-CSF in this regimen for mechanistic reasons. Leukine has been studied extensively in combination with dinutuximab and naxitamab leading to improved patient outcomes. As a result, all clinical trials supporting the FDA-approval of dinutuximab and naxitamab included Leukine and both products are labeled for use in combination with GM-CSF. "The pleiotropic effects of Leukine contribute to its important role as an immunomodulatory adjuvant in combination with anti-GD2 mAbs," noted Jaume Mora, M.D., Ph.D., Scientific Director of Oncology and Hematology at Sant Joan de Déu Barcelona Children's Hospital and lead author of the publication. "GM-CSF stimulates neutrophils and macrophages leading to increased cellular phagocytosis and increased ADCC. Further, GM-CSF increases major histocompatibility complex (MHC) class II expression which enhances tumor antigen presentation on dendritic cells that can mediate T cell antitumor effects. For all of these mechanistic reasons, Leukine is a critical component of anti-GD2 therapy." The figure below from the publication depicts these mechanisms. Reference 1Mora J, Modak S, Kinsey J, Ragsdale CE, Lazarus HM. GM-CSF, G-CSF or no cytokine therapy with anti-GD2 immunotherapy for high-risk neuroblastoma. Int J Cancer. 2023 Dec 18. doi: 10.1002/ijc.34815. ABOUT LEUKINE LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. The product is commercially available in the United States and accessible through a named patient program operated by Tanner Pharma Group outside of the United States. LEUKINE is indicated: To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML). For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients. For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older. For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older. For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older. To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]). Important Safety Information for Leukine (sargramostim) Contraindications Do not administer LEUKINE to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of LEUKINE. Warnings and Precautions Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If a serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy, and institute medical management. Discontinue LEUKINE permanently for patients with serious allergic reactions. LEUKINE can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed. LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after LEUKINE administration. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored. Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease. If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half. Monitor complete blood counts (CBC) with differential twice per week. Discontinue LEUKINE therapy if tumor progression, particularly in myeloid malignancies, is detected during LEUKINE treatment. Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed. Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants. Drug Interactions Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects. Adverse Reactions Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are: In recipients of autologous bone marrow transplantation (BMT)–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder In recipients of allogeneic BMT–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin In patients with AML–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema ABOUT PARTNER THERAPEUTICS Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit . SOURCE Partner Therapeutics, Inc.

Initial data continue to support advancement of mavorixafor into pivotal, global Phase 3 trial in certain chronic neutropenic disorders; company on track to initiate in 1H 2024 X4 expects to present additional CN Phase 2 clinical trial data in 1H 202 X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced the presentation of additional preliminary data from its ongoing Phase 2 clinical trial evaluating the safety and efficacy of once-daily oral mavorixafor with or without concurrent treatment with injectable granulocyte-colony stimulating factor (G-CSF) in people diagnosed with idiopathic, cyclic, or congenital neutropenia. Julia T. Warren, M.D., Ph.D., a trial investigator and hematologist in the Division of Hematology at the Children’s Hospital of Philadelphia, will be presenting Poster #P1160 today at the annual meeting of the Annual Society of Hematology (ASH). The poster highlights case studies of the first three participants to complete the 6-month Phase 2 trial, all of whom entered the study on G-CSF therapy. Overall: Mavorixafor was generally well tolerated when used in combination with G-CSF, with no serious adverse events reported; While 4 infections were reported during the first two months of the trial, no infections were reported during the following 4 months of the trial, despite reductions in G-CSF dosing in two of the three participants; The data continue to support the potential of mavorixafor to raise absolute neutrophil counts (ANC) and enable reduction in G-CSF dosing in patients with chronic neutropenia; The data informed the design of the planned pivotal, global Phase 3 clinical trial of mavorixafor in certain chronic neutropenic disorders, as well as the selection of ANC and infection as primary endpoints; the trial is expected to initiate in the first half of 2024. The poster also highlighted results from a recent qualitative Chronic Neutropenia Patient Voice Survey that confirmed previous market research showing respondents' strong interest in reducing G-CSF dosing and/or reducing injection frequency with the addition of an oral medication such as mavorixafor. “Given that there has been little innovation in the classical hematology space and no innovation for patients with chronic neutropenia for the past 30 years, we are very pleased with the data continuing to emerge from our ongoing CN Phase 2 clinical trial,” said Christophe Arbet-Engels, M.D., Ph.D., Chief Medical Officer of X4 Pharmaceuticals. “In the first half of 2024, we look forward to presenting more comprehensive data from this Phase 2 trial, which will include both mavorixafor monotherapy treatment data as well as additional results of participants on mavorixafor/G-CSF combination therapy.” X4 Pharmaceuticals is a late-stage clinical biopharmaceutical company driven to improve the lives of people with rare diseases of the immune system. Our lead clinical candidate is mavorixafor, a small molecule antagonist of chemokine receptor CXCR4 that is being developed as an oral, once-daily therapy across a variety of immunodeficiencies, including WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome and certain chronic neutropenic disorders. Following successful completion of a global, pivotal, Phase 3 clinical trial, we are seeking U.S. regulatory approval of oral, once-daily mavorixafor for the treatment of people aged 12 years and older with WHIM syndrome. We are also currently planning a Phase 3 clinical program evaluating mavorixafor in certain chronic neutropenic disorders. We continue to leverage our insights into CXCR4 and immune system biology at our corporate headquarters in Boston, Massachusetts and at our research center of excellence in Vienna, Austria. For more information, please visit our website at www.x4pharma.com. The content above comes from the network. if any infringement, please contact us to modify.