frenlosirsen (ION251) / Ionis - LARVOL DELTA

Safety, tolerability and molecular correlates of the IRF4-targeted antisense oligonucleotide frenlosirsen in patients with relapsed/refractory multiple myeloma: A phase 1a dose escalation trial (AACR 2025) - "Abstract is embargoed at this time."

Clinical • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • IRF4

Antisense oligonucleotides-based approaches for the treatment of multiple myeloma. (PubMed, Int J Biol Macromol) - "So far, pre-clinical and clinical studies showed promising results when Bcl-2 (Genasense), Mcl-1 (ISIS2048), STAT3 (ISIS345794) and IRF4 (ION251) were targeted using ASOs-based formulations. The relevant genetic targets in ASOs-based MM therapies were described, and the research results obtained in the studies conducted so far were analyzed, with a focus on the ASOs formulations that were already included in clinical trials. In the end, current challenges, and future perspectives of antisense therapy for MM were also discussed."

Journal • Review • Bone Marrow Transplantation • Gene Therapies • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • BCL2 • IL6 • IRF4 • MCL1 • MYC • STAT3

A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jan 2024 ➔ Sep 2024 | Trial primary completion date: Jan 2024 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | N=80 ➔ 23

Enrollment change • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Preoperative carbon nanoparticle injection improves inferior mesenteric artery lymph node retrieval in patients with rectal cancer. (PubMed, Surgery) - "The preoperative submucosal injection of carbon nanoparticles was helpful for increasing the number of station 253 nodes harvested, and a minimum of 4 examined station 253 nodes was necessary for standard D3 lymph node dissection in rectal cancer."

Clinical • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

[VIRTUAL] Agnathia-Otocephaly Complex With Short Lower Limbs: A Rare Case Report (CAP 2021) - "About 135 cases have been reported since the first description 251 years ago...Pathogenesis is considered to be a defect of blastogenesis, primarily involving the first branchial arch derivatives along with dysmorphogenesis of other midline craniofacial field structures. This case of AGOTC is unique in that it expands the associated malformations to include bilateral short lower limbs."

Clinical • Hematological Disorders • Small for Gestational Age • PRRX1

[VIRTUAL] SESSION 251: Lung disease burden and management (ERS 2021) - "Participants and chairs of the session are invited to access all e-posters from 23 August to 4 September prior to the 1-hour live, online discussion scheduled from September 5-7. Please note that during live discussion there will be NO e-poster/abstract presentations, only discussion."

Pulmonary Disease • Respiratory Diseases

BAOMS QOMS: findings from the pilot phase and lessons learned in the feasibility evaluation of a national quality improvement initiative. (PubMed, Br J Oral Maxillofac Surg) - "The pilot was successful in aiding the project team identify areas of weaknesses and strength in the design of the REDCap registry and implementation of the next phase of the initiative. The information and experience gained has to date enabled a successful application for section 251 approval from the HRA and progress for the next phase of national data collection."

Journal • Mood Disorders • Oncology

Guidance for researchers wanting to link NHS data using non-consent approaches: a thematic analysis of feedback from the Health Research Authority Confidentiality Advisory Group. (PubMed, Int J Popul Data Sci) - "Securing Section 251 approval poses ethical, practical and governance challenges. However, through a comprehensive, planned approach Section 251 approval is possible, enabling researchers to unlock the potential of linked data for the purposes of health research."

Journal

"Maybe ION251 might steal the day eventually.... https://t.co/DrA7o7dgnn" (@voteyesireland)

Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption. (PubMed, Cell Stem Cell) - "In a patient-derived xenograft model that recapitulates IRF4 pathway activation in human myeloma, we test the effects of IRF4 antisense oligonucleotides (ASOs) and identify a lead agent for clinical development (ION251)...Mechanistically, IRF4 inhibition disrupts cell cycle progression, downregulates stem cell and cell adhesion transcript expression, and promotes sensitivity to myeloma drugs. These findings will enable rapid clinical development of selective IRF4 inhibitors to prevent myeloma progenitor-driven relapse."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=80; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Manganese-enhanced magnetic resonance imaging in dilated cardiomyopathy and hypertrophic cardiomyopathy. (PubMed, Eur Heart J Cardiovasc Imaging) - "The rate of manganese uptake in both dilated and hypertrophic cardiomyopathy provides a measure of altered myocardial calcium handling. This holds major promise for the detection and monitoring of dysfunctional myocardium, with the potential for early intervention and prognostication."

Journal • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology

[VIRTUAL] POPULATION-BASED ASCERTAINMENT OF WILSON’S DISEASE IN ENGLAND: A NATIONAL RARE DISEASE REGISTER (AASLD 2020) - " NCARDRS has legal permission under section 251 of the NHS 2016 Act ((CAG 10-02(d)/2015)) which permits collection of health data information without patient consent... Surveillance of rare diseases, such as WD, is key in improving care and quality of life for these populations and informing health service planning. During the development of the WD registry, our experience has been that clinician notification only risks disengagement as workload pressures and differences in local systems make it a time-consuming exercise and often selects for participation mostly from specialist centres. By using NCARDRS unique legal permission to link available national and clinical datasets to identify cases, we have established a WD patient registry which is not limited by clinician participation to gain a more accurate idea of prevalence with less bias."

Clinical • Hepatology • Metabolic Disorders • Movement Disorders • Rare Diseases • Transplantation

Liaison psychiatry-measurement and evaluation of service types, referral patterns and outcomes (LP-MAESTRO): a protocol. (PubMed, BMJ Open) - "The Confidentiality Advisory Group at the Health Research Authority determined that Section 251 approval under Regulation 5 of the Health Service (Control of Patient Information) Regulations 2002 was not required for the study 'on the basis that there is no disclosure of patient identifiable data without consent' (REF: 16/CAG/0037).Results of the study will be published in academic journals in health services research and mental health. Details of the study methodology will also be published in an academic journal. Discussion papers will be authored for health service commissioners."

Clinical • Journal • Psychiatry

Towards UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): protocol for an evaluation of the requirements for arthroplasty follow-up, and the production of consensus-based recommendations. (PubMed, BMJ Open) - "Section 251 support (17/CAG/0030) and NHS Digital approval (DARS-NIC-172121-G0Z1H-v0.11) have been obtained for WP2a (NJR-HES-PROMS). ISAC (11_050MnA2R2) approval has been obtained for WP2a (CPRD-HES)."

Clinical • Journal • Musculoskeletal Diseases • Orthopedics

A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=80; Not yet recruiting; Sponsor: Ionis Pharmaceuticals, Inc.

Clinical • New P1 trial • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology