Leukotac (inolimomab) / Mediolanum Pharma - LARVOL DELTA

Examining the Long-term Clinical Evidence of Therapies for Inflammatory Bowel Disease in Bio-naïve Patients: Episode 17 Biosimilar Treatment Options for Patients With UC (HCPLive) - "Experts discuss the recent use of biosimilars like inolimomab as treatment for ulcerative colitis (UC)."

Video

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials. (PubMed, Front Immunol) - "Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy. Further well-designed RCTs and integrated studies are required to determine the optimal treatment. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487."

Clinical • Retrospective data • Review • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

A Phase I/II Study on the Anti-CD3/CD7 Immunotoxin Combination (T-GuardTM) for the Treatment of Steroid-Refractory Acute Gvhd (ASH 2017) - P1/2; "...The outcomes compared favorably with historical controls receiving either infliximab (N=21) or inolimomab/etanercept (N=21) were the ORR was 52% and the 6-month OS 29% (Figure 1 and 2)...Treatment of SR-aGVHD with a short course of the T-GuardTM proved to be safe and well tolerated, and resulted in a high rate of CR and a promising 6-month OS of 60%, especially considering the high-risk setting (90% GI involvement, 50% high-risk biomarker profile). A pivotal multicentre international controlled trial, comparing T-GuardTM with best-available therapy for SR-aGVHD is scheduled for the end of 2017."

Biomarker • Clinical • P1/2 data • Biosimilar • Cytomegalovirus Infection • Graft versus Host Disease • Leukemia • Venous Thromboembolism

Meta-analysis of the effectiveness and safety of Shenyankangfu tablets combined with losartan potassium in the treatment of chronic glomerulonephritis. (PubMed, PLoS One) - "It is safer to treat chronic glomerulonephritis with Shyenyankangfu tablets in combination with losartan potassium. At the same time, it alleviates disease-related symptoms, reduces the influence of cytokine levels, and has fewer adverse reactions, making it more conducive to disease recovery. However, additional multi-center, randomized, control trials with large sample sizes must be conducted to confirm the findings."

Journal • Retrospective data • Glomerulonephritis • Lupus Nephritis • Nephrology

Bacteroides thetaiotaomicron uses a widespread extracellular DNase to promote bile-dependent biofilm formation. (PubMed, Proc Natl Acad Sci U S A) - "We determined that bile-dependent biofilm formation involves the production of the DNase BT3563 or its homologs, degrading extracellular DNA (eDNA) in several B. thetaiotaomicron strains. Our study therefore shows that, although biofilm matrix eDNA provides a biofilm-promoting scaffold in many studied Firmicutes and Proteobacteria, BT3563-mediated eDNA degradation is required to form B. thetaiotaomicron biofilm in the presence of bile."

Journal

Meta-Analysis of Interleukin-2 Receptor Antagonists as the Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease. (PubMed, Front Immunol) - "The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74-0.87)] and 0.71 (95% CI: 0.56-0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39-0.68) and denileukin diftitox 0.56 (95% CI: 0.35-0.76). The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs."

Retrospective data • Review • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation • IL2RA

Early Access Program With Inolimomab in Steroid-refractory Acute Graft Versus Host Disease (clinicaltrials.gov) - P=N/A; N=N/A; Available; Sponsor: ElsaLys Biotech

Clinical • New trial • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

While ElsaLys continues to work on the filing of marketing approval in Europe and the U.S. for inolimomab, the company confirms the renew of its cohort ATU in France and compassionate use programs submissions in several other countries (GlobeNewswire) - "ElsaLys Biotech confirmed that The French National Agency for the Medicines and Health Products Safety (ANSM) has renewed the Temporary Authorisation for Use (ATU) so-called cohort ATU (cATU) for inolimomab (LEUKOTAC®) on December 24, 2020. This renewed authorization includes the implementation of a reinforced monitoring…of the efficacy and safety data obtained in patients treated within the framework of this cATU....Around 30 patients in France have been treated with inolimomab as it is considered a reliable treatment of this high-risk patient population....'Inolimomab is already being administered in France before marketing autorisation in Europe and hopefully soon in other countries through compassionate use programs'...'Data on clinical benefit and safety profile we expect to collect through these compassionate use programs will support our work on the filing of marketing authorization applications (MAA) in Europe and in the U.S'."

Clinical • European regulatory • Graft versus Host Disease

Consortium including ElsaLys Biotech and Novadiscovery awarded €3.35 million by Bpifrance to advance inolimomab in graft-versus-host disease (GlobeNewswire) - "The Silikotac Program consortium, consisting of ElsaLys Biotech, Novadiscovery ('NOVA') and two expert academic teams from Hôpital St Louis (Paris) and Hôpital Henri Mondor (Paris), has been awarded €3.35 million in non-dilutive funding by Bpifrance to support development of inolimomab in graft-versus-host disease (GvHD)...The ambition of the Silikotac Program is to create the first French industrial and scientific immunotherapy chain group focused on GvHD....NOVA, which has been awarded €2.4 million, will conduct in silico clinical trials utilising its innovative Jinkō® platform. The results will be used to support future regulatory approval applications by ElsaLys for inolimomab in Europe."

Financing • Graft versus Host Disease

Adverse events in second- and third-line treatments for acute and chronic graft-versus-host disease: systematic review. (PubMed, Ther Adv Hematol) - "Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab). The reported incidence of infectious AEs in aGvHD and grade 3-5 AEs in cGvHD was lower on ECP compared with pharmaceutical management."

Adverse events • Journal • Review • Graft versus Host Disease • Immunology • Transplantation

EiFFEL: Evaluation of EFficacy and SaFEty of Leukotac (Inolimomab) in Pediatric Patients With SR-aGvHD (clinicaltrials.gov) - P3; N=65; Not yet recruiting; Sponsor: ElsaLys Biotech; Initiation date: Oct 2020 ➔ Oct 2021

Clinical • Trial initiation date • Graft versus Host Disease • Immunology • Pediatrics

[VIRTUAL] Mesenchymal Stromal Cell (MSC) Compassionate Use in France in Treatment of Steroid-Refractory Graft-Versus-Host-Disease (GVHD) after Approval By the Expert Committee of Société Française De Greffe De Moelle Et Thérapie Cellulaire (SFGM-TC) (ASH 2020) - "All pts received a ciclosporin-based (CSA) GVHD prophylaxis (CSA alone, n=1; CSA + Mycophenolate Mofetil (MMF) or Methotrexate, n=7)...Five pts were still taking corticosteroids, and six were taking additional immunosuppressive molecules (Tacrolimus, Ruxolitinib, Etanercetp, Inolimomab, MMF) at time of MSC infusion...Besides, we included patient suffering from R-cGVHD. Regarding those results, MSC efficacy and safety should be confirmed in a proper clinical trial."

Graft versus Host Disease • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Transplantation

[VIRTUAL] Genomic landscape of syndromic and non-syndromic retinitis pigmentosa in a rare eye disease referral centre in Portugal (EURETINA 2020) - "In BBS, one case was BBS1-related, while the remaining 4 were BBS10... Achieving strong population–based data is the first step towards better genetic and prognostic counselling as well as guidance for future therapeutic interventions. Overall, this study achieved a highly satisfactory detection rate (75.0%; 63/84) of disease-causing genotypes using clinically-oriented genetic testing. In non-syndromic RP, 65.8% of solved cases were caused by 5 genes: EYS, RPGR, IMPG2, RHO and RPE65."

Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • MERTK • USH2A

[VIRTUAL] Effect of primary cilium-associated genes expression on the survival of mesothelioma patients: In silico investigation of TCGA data. (ERS 2020) - "We investigated data for the BBS (BBS10; MKKS; ARL6; LZTFL1; BBS12), BBSome (BBS1; BBS2; BBS4; BBS5; BBS7; BBS8; BBS9) and Kinesin-II (KIF3A; KIFAP3; KIF3B) components of the PC in relation to survival, tumor histology, cancer stage and gender... Our findings indicate the prognostic relevance of the BBS2 and BBS12 genes expression in mesothelioma. Future investigation of these genes is needed to provide information on the exact roles of PC components in mesothelioma development."

Clinical • Lung Cancer • Mesothelioma • Oncology • Solid Tumor

[VIRTUAL] Multi-Omics Analysis of the PDGF Response in Pulmonary Vascular Smooth Muscle Cells from Patients with Pulmonary Arterial Hypertension: Implication of the NMDAR (ERS 2020) - "PASMC of PAH patients and controls in culture were stimulated with PDGF-BB 10 μM for 24 h and exposed to 100 μM MK-801, a noncompetitive NMDAR antagonist. Multi-omics analysis showed that PDGF induced pro-proliferative gene and protein expression tended to normalize using NMDAR in PASMC. These results further support NMDARs as a therapeutic target for the treatment of PAHs."

Clinical • Hypertension • Pulmonary Arterial Hypertension

[VIRTUAL] Multi-Omics Analysis of the PDGF Response in Pulmonary Vascular Smooth Muscle Cells from Patients with Pulmonary Arterial Hypertension: Implication of the NMDAR (ATS-I 2020) - "PASMC of PAH patients and controls in culture were stimulated with PDGF-BB 10 μM for 24 h and exposed to 100 μM MK-801, a noncompetitive NMDAR antagonist. Multi-omics analysis showed that PDGF induced pro-proliferative gene and protein expression tended to normalize using NMDAR antagonists in PASMC. These results further support NMDARs as a therapeutic target for the treatment of PAHs."

Clinical • Hypertension • Oncology • Pulmonary Arterial Hypertension

ElsaLys Biotech announces submission of Biologics License Application to FDA for LEUKOTAC (inolimomab) for the treatment of graft-versus-host disease in adult patients (GlobeNewswire) - "ElsaLys Biotech...announced today the U.S. Food and Drug Administration (FDA) agreement to start the LEUKOTAC® (inolimomab) submission process for a Biologics License Application (BLA) for the treatment of Steroid-Refractory acute graft-versus-host disease (aGvHD), grade II-IV adult patients....Reviewed under the FDA’s Real-Time Oncology Review pilot program...The next step in the BLA Submission process to the FDA will be the Chemistry, Manufacturing and Controls (CMC) pre-BLA meeting in September 2020."

BLA • FDA event • Graft versus Host Disease • Inflammation

Spatial and temporal dynamics of respiratory syncytial virus infections in New South Wales and Western Australia (ECCMID 2019) - "Each subtype, regardless of location, was dominated by a single genotype (RSV-A/ON1-like and RSV-B/BA10-like).  Our WGS analysis identified a number of features of RSV epidemiology including i) the co-circulation of both subtypes RSV-A and RSV-B; ii) a single genotype for each subtype predominates each season; iii) multiple distinct sub-lineages of each genotype co-circulate and are associated with regional and local clustering/outbreaks and iv) viral mixing is apparent despite geographic clustering."

Infectious Disease

Steroids vs. steroids plus additional agent in frontline treatment of acute graft-versus-host disease: a systematic review and meta-analysis of randomized trials. (PubMed) - Biol Blood Marrow Transplant - "In conclusion, these results argue against the value of augmented generic immunosuppression beyond steroids for frontline treatment of aGvHD and emphasize the importance of developing alternative strategies. Novel forms of immunomodulation and targeted therapies against non-immune-related pathways may enhance the efficacy of steroids in this setting and early predictive and prognostic biomarkers can help identify the subgroup of patients that would likely need treatments other than (or in addition to) generic immunosuppression."

Biomarker • Journal • Biosimilar • Graft versus Host Disease

Multi-Omics Analysis of the PDGF Response in Pulmonary Vascular Smooth Muscle Cells from Patients with Pulmonary Arterial Hypertension: Implication of the NMDAR (ATS 2020) - "PASMC of PAH patients and controls in culture were stimulated with PDGF-BB 10 μM for 24 h and exposed to 100 μM MK-801, a noncompetitive NMDAR antagonist. Multi-omics analysis showed that PDGF induced pro-proliferative gene and protein expression tended to normalize using NMDAR antagonists in PASMC. These results further support NMDARs as a therapeutic target for the treatment of PAHs."

Clinical

EiFFEL: Evaluation of EFficacy and SaFEty of Leukotac (Inolimomab) in Pediatric Patients With SR-aGvHD (clinicaltrials.gov) - P3; N=65; Not yet recruiting; Sponsor: ElsaLys Biotech

Clinical • New P3 trial

Long-term follow-up of a phase 3 clinical trial of inolimomab for the treatment of primary steroid refractory aGVHD. (PubMed, Blood Adv) - No abstract available

Clinical • Journal • P3 data

LEUKOTAC (inolimomab) is available again in France, following the granting of cohort ATU for the treatment of graft-versus-host disease, corticosteroid-resistant or corticosteroid-dependent, with grade II-IV (GlobeNewswire, Elsalys Biotech) - "LEUKOTAC ® (inolimomab) is available again in France, following the granting of cohort ATU for the treatment of graft-versus-host disease, corticosteroid-resistant or corticosteroid-dependent, with grade II-IV. The French National Agency for the Medicines and Health Products Safety (ANSM) granted a Temporary Authorisation for Use (ATU) so-called cohort ATU (cATU) for LEUKOTAC® (inolimomab) on December 24, 2019."

Clinical • Launch Europe • Regulatory

Optical coherence tomography grading of retinopathy associated with bardet-biedl syndrome (EURETINA 2019) - "BBS1 gene mutation was the most common (25/44), followed by BBS10 (3/44), BBS2 (2/44), BBS5 (2/44), BBS12 (1/44), INPP5E (1/44) and no result in 10 cases.19 patients with BBS 1 gene mutations had gradable scans... We have described a novel grading system, based primarily on structural changes detected by standard SD-OCT. Each grade represents a change in retinal architecture (in a continuing spectrum of progression of retinal degeneration) that is easily identified and maybe used clinically to extrapolate an assessment of visual function (based on published evidence of OCT features – visual functional correlations). Furthermore, this grading system may help in accurate objective monitoring of disease progression and also serve as a useful objective endpoint in clinical trials for BBS."

Generation of induced pluripotent stem cells, KCi002-A derived from a patient with Bardet-Biedl syndrome homozygous for the BBS10 variant c.271insT. (PubMed, Stem Cell Res) - "Here we describe the successful generation of an induced pluripotent stem cell (iPSC) line KCi002-A from a male with BBS, homozygous for the disease causing variant c.271insT, p.(Cys91fsX95) in BBS10. Resource table."

Clinical • Journal