Methylprednisolone

On December 18, 2024, the Food and Drug Administration approved remestemcel-L-rknd (Ryoncil, Mesoblast, Inc.), an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy, for steroid-refractory acute graft versus host disease (SR-aGVHD) in pediatric patients 2 months of age and older. Ryoncil is the first FDA-approved MSC therapy.Full prescribing information for Ryoncil will be posted hereEfficacy and SafetyEfficacy was evaluated in MSB-GVHD001 (NCT02336230), a multicenter, prospective, single-arm study in 54 pediatric patients with SR-aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Patients had Grade B to D SR-aGVHD, excluding Grade B skin alone (International Blood and Marrow Transplantation Registry Severity Index Criteria). SR-aGVHD was defined as aGVHD progressing within 3 days or not improving within 7 consecutive days of methylprednisolone (2 mg/kg/day or equivalent). Patients receiving a second-line aGVHD therapy prior to screening were excluded.The main efficacy outcome measures were overall response rate (ORR) at Day 28 and duration of overall response. The ORR included complete and partial response rates (CR and PR). ORR at Day 28 was 70% (95% confidence interval, CI: 56.4, 82.0), including a CR rate of 30% (95% CI: 18.0, 43.6) and a PR rate of 41% (95% CI: 27.6, 55.0). The median duration of response calculated from response at Day 28 to either progression, new systemic therapy for aGVHD, or any cause death, was 54 days (range 7, 159+).The most common nonlaboratory adverse reactions (incidence ≥20%) were viral infectious disorders, bacterial infectious disorders, infection – pathogen unspecified, pyrexia, hemorrhage, edema, abdominal pain and hypertension.The recommended dose is 2 X 106 MSC/kg body weight per intravenous infusion given twice a week for 4 consecutive weeks for a total of 8 infusions. Infusions are administered at least 3 days apart. Treatment may be continued based on response at 28 days after initial remestemcel-L-rknd.Expedited ProgramsRemestemcel-L-rknd has fast track, orphan drug and priority review designations. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. A description of FDA expedited programs for regenerative medicine advanced therapies is in the Guidance for Industry: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products regulated by the Center for Biologics Evaluation and Research, healthcare professionals may email OTPRPMS@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.

All Three Patients Treated in First Dose Cohort Administered Fludarabine-free Conditioning and Show Rapid, Deep, and Sustained B-cell Depletion with Favorable Safety Profile First Patient to Reach 6-Month Follow-up Remains in DORIS Clinical Remission and Free of All Immunosuppressive Therapies Company Plans to Initiate Dose Expansion at First Dose Level of 360M Cells SAN DIEGO, Dec. 09, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented new clinical and translational data from the Company’s FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus (SLE) at the American Society of Hematology (ASH) Annual Meeting being held in San Diego, CA. The first three study patients, each of whom presented with active lupus nephritis (LN) despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning followed by a single dose of FT819 at 360 million cells. There were no dose-limiting toxicities (DLTs), no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD), and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. FT819 is the Company’s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking. “We continue to be very pleased with early clinical observations of fludarabine-free conditioning and FT819 off-the-shelf, CAR T-cell therapy in patients with moderate-to-severe SLE. The remarkable experience of the first patient treated in April is ongoing, as the patient remains on-study in drug-free clinical remission. In addition, the initial clinical and translational data from the two additional patients treated at the first dose level continue to support the potential for disease transformation,” said Bob Valamehr, President of Research and Development of Fate Therapeutics. “We are now initiating dose expansion at this first dose level to accelerate development, and are also escalating dose based on the favorable safety profile observed. In addition, I am pleased to announce that the first patient has now been treated with FT819 as an add-on to maintenance therapy without conditioning chemotherapy. We believe our therapeutic approach is highly-differentiated and has the potential to transform disease outcomes without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization.” FT819 Phase 1 Autoimmunity Study The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe SLE is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819 (NCT06308978). The first three patients, all of whom presented with active LN despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either cyclophosphamide alone or bendamustine alone, followed by a single dose of FT819 at 360 million cells. In all three patients, FT819 was detected in the peripheral blood and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. All three patients remain on-study, and there have been no DLTs and no events of any grade of CRS, ICANS, or GvHD. Based on these clinical observations, the Company is initiating dose expansion in up to 10 patients at this first dose level, and is also escalating dose to 720 million cells. The Company’s FT819 Phase 1 Autoimmunity study also includes a second treatment arm to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The first patient has now been treated in this second arm, which is being conducted in parallel with the study’s conditioning arm. FT819 Patient 1 Case Study The first patient treated in the Phase 1 Autoimmunity study presented with active LN and severe disease, which was marked by renal BILAG A (British Isles Lupus Assessment Group) disease activity score based on biopsy, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score of 20, FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) score of 33 (range 0-52, where a score of 52 indicates no fatigue) and PGA (Physician Global Assessment) score of 2.5 (where a score of 3 indicates most severe activity). Following administration of fludarabine-free conditioning and treatment with a single dose of FT819 at 360 million cells, the patient was discharged from the hospital without notable adverse events (AEs) after a protocol-required three-day stay. Rapid elimination of CD19+ B cells in the periphery was observed following treatment, and B-cell recovery by Month 3 was predominantly comprised of naïve, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. The patient reported that her debilitating fatigue had entirely resolved without further treatment, and treatment with methylprednisolone was discontinued at Month 3. The patient achieved DORIS (definition of remission in SLE) clinical remission, including with resolution of arthritis and active urinary sediment and with a substantial reduction in proteinuria, as of Month 6 follow-up. The patient continues on-study, in DORIS clinical remission, and remains free of all immunosuppressive therapy. iPSC-derived CAR T-cell Product Platform The Company also highlighted the scientific progress of its proprietary iPSC-derived CAR T-cell product platform at the ASH Annual Meeting. In an oral presentation entitled “Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy”, the Company compared its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO) to both target and evade host alloreactive immune cells, to other host immune evasion strategies. In preclinical studies of allogeneic models, the Company showed that its Sword and Shield Technology specifically engaged with alloreactive T cells and supported functional persistence while avoiding the killing of general host T cells and activated anti-tumor T cells. This unique observation was not seen with other approaches that are either too broad and undesirably eliminate most of the host immune system or have limited coverage and cannot adequately protect the allogeneic cell product. In a second presentation entitled “Development of Induced Pluripotent Stem Cell-Derived T Cells Exhibiting Phenotypic and Functional Attributes of Primary CAR T Cells”, the Company conducted a series of high-resolution analyses to show stimulated iPSC-derived T cells elicit primary T-cell like activation, proliferation, transcriptional and functional program engagement, and iPSC-derived CAR T cells uniquely emulate antigen-mediated response similar to primary-derived autologous CAR T cells. About Fate Therapeutics’ iPSC Product Platform Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications. About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Company’s iPSC-derived CAR T-cell product candidates, including FT819, the advancement of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the Company’s progress, plans and timelines for the clinical investigation of its product candidates, including the expected clinical development plans for FT819, the initiation and continuation of enrollment in the Company’s clinical trials, the initiation of additional clinical trials and additional dose cohorts in ongoing clinical trials of the Company’s product candidates, the timing and availability of data from the Company’s clinical trials, the therapeutic and market potential of the Company’s research and development programs and product candidates, the Company’s clinical and product development strategy, and the Company’s expectations regarding progress, plans, and timelines. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company’s research and development programs and product candidates, including those product candidates in clinical investigation, may not demonstrate the requisite safety, efficacy, or other attributes to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the initiation and conduct of, or enrollment of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Company’s product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company’s ongoing and planned clinical trials, difficulties or delays in manufacturing or supplying the Company’s product candidates for clinical testing, failure to demonstrate that a product candidate has the requisite safety, efficacy, or other attributes to warrant further development, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time in the Company’s press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise. Contact: Christina TartagliaPrecision AQ212.362.1200christina.tartaglia@precisionaq.com