CD20 inhibitors(B-lymphocyte antigen CD20 inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects), CD20-directed cytolytic effects

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [3]

Active Indication-

Inactive Indication

Aggressive B-Cell Non-Hodgkin LymphomaAnaplastic Large-Cell LymphomaB-cell lymphoma refractory+ [12]

Originator Organization

Immunomedics, Inc.

Active Organization-

Inactive Organization

Immunomedics, Inc.

Takeda Pharmaceutical Co., Ltd.

Gilead Sciences, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

Gene Sequence

Sequence Code 52152L

Source: *****

Sequence Code 10069122H

Source: *****

Clinical Trials associated with Veltuzumab

IRCT20160422027520N11 / SuspendedPhase 2/3

Effects of Anti-CD20 monoclonal antibody on immunologic factors in elderly patients with ischemic stroke

Start Date20 May 2019

Sponsor / Collaborator

Tabriz University of Medical Sciences

ISRCTN37116985 / CompletedPhase 1/2IIT

Therapy of type 1 diabetes with ex-vivo expanded CD4+CD25+CD127- T regulatory cells (Tregs) and anti-CD20 monoclonal antibody – a randomized trial

Start Date02 Jun 2015

Sponsor / Collaborator-

NCT01390545 / TerminatedPhase 2

VELVET (Veltuzumab Various Doses Exploratory Trial), a Randomized, Double Blind, Placebo Controlled, Multicentre, Multinational Phase II Dose Range Finding Trial in Subjects With Moderate to Severe Rheumatoid Arthritis Insufficiently Controlled With Either Methotrexate Alone or Methotrexate Plus Anti-tumour Necrosis Factor Biological Treatment, Comparing 3 Different Subcutaneous Dosages of Anti-CD20 Monoclonal Antibody Veltuzumab to Placebo as an add-on Therapy to Methotrexate.

This is a multi-national, multi-centre, placebo-controlled, double-blind, randomized, 4-arm parallel group trial, comparing three different dose levels (80 mg, 160 mg and 320 mg) of veltuzumab to placebo, administered weekly (days 1, 8, 15 and 22) by subcutaneous (sc) injection to subjects with moderate to severe rheumatoid arthritis (RA) (cumulative veltuzumab doses 320 mg, 640 mg, and 1280 mg, respectively). All subjects will be on continued stable co-medication with methotrexate (MTX).

Start Date01 Aug 2011

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

100 Clinical Results associated with Veltuzumab

100 Translational Medicine associated with Veltuzumab

100 Patents (Medical) associated with Veltuzumab

1,788

Literatures (Medical) associated with Veltuzumab

01 Feb 2024·The Lancet. Haematology

Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study

Article

Author: Panizo, Carlos ; Triguero, Ana ; Sharma, Sunil ; Banerjee, Lalita ; Abrisqueta, Pau ; González-Barca, Eva ; Bastos-Oreiro, Mariana ; Pérez, José María Arguiñano ; Jin, Hyun Yong ; Musick, Lisa ; McMillan, Andrew ; Seymour, Erlene ; Hirata, Jamie ; de Guzman, Jayson ; Miall, Fiona ; Diefenbach, Catherine

BACKGROUND:

Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma.

METHODS:

This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK). Patients (≥18 years old) were eligible for inclusion if they had histologically documented CD20-positive relapsed or refractory diffuse large B-cell lymphoma and Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. The dose-escalation phase (1b) used escalating doses of lenalidomide to find the recommended phase 2 dose. Patients received six 28-day cycles of induction treatment with intravenous rituximab 375 mg/m² and intravenous polatuzumab vedotin 1·8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1-21 of each 28-day cycle. During the dose-expansion phase (2), patients received six 28-day cycles of Pola+R+Len at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response or partial response at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m² on day 1 and lenalidomide 10 mg/day on days 1-21 of each 28-day cycle for a maximum of 6 cycles. The primary safety objective of the dose-escalation phase was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. The primary efficacy outcome of the dose-expansion phase was Independent Review Committee-assessed complete response rate at end of induction, based on PET-CT. Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02600897.

FINDINGS:

Between July 11, 2017 and Feb 3, 2020, 57 patients were enrolled (median age 71 years [IQR 60-75]; 38 [67%] were male and 19 (33%) were female; 47 [82%] were not Hispanic or Latino; and the median previous lines of therapy was 2 [IQR 1-3]). 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide. After a median follow-up of 11·8 months (IQR 4·7-25·8), the complete response rate, as assessed by the Independent Review Committee, was 31% (90% CI 20-43). The most common grade 3-4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (eight [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients and one patient died due to a treatment-related adverse event (neutropenic sepsis).

INTERPRETATION:

Although the combination of Pola+R+Len did not meet the prespecified activity threshold, some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma.

FUNDING:

Genentech/F Hoffmann-La Roche.

01 Feb 2024·Multiple sclerosis and related disorders

Ocrelizumab in highly disabled progressive multiple sclerosis patients

Article

Author: Howard, Danielle ; Houtchens, Maria

BACKGROUND:

Ocrelizumab is a commonly used anti-CD20 monoclonal antibody with efficacy in the treatment of both relapsing-remitting (RRMS) and primary progressive (PPMS) multiple sclerosis. Real world use of ocrelizumab in MS patients with higher levels of motor disability requiring a walker or a wheelchair is not well characterized as these populations were excluded from initial studies. Higher levels of disability may be a barrier to treatment access. This study aimed to describe the access to, and tolerability and therapeutic outcomes of ocrelizumab in highly disabled MS patients in a real-world setting.

METHODS:

As part of an ongoing study of ocrelizumab treatment access, barriers, and outcomes in MS patients at the Brigham MS Center, we retrospectively reviewed all patients with an Expanded Disability Status Scale (EDSS) of 6.5 or greater at the time of ocrelizumab initiation. All patients were started on ocrelizumab by their treating providers prior to this study initiation. Patients were excluded for recent rituximab exposure, co-treatment with more than one immunosuppressant, or alternative diagnoses contributing to high EDSS. Data was collected on incidence and severity of side effects while on ocrelizumab, persistence of treatment beyond one year, and MS stabilization versus progression while on this treatment.

RESULTS:

Of the 1219 patients on ocrelizumab between 2017 and 2021, 113 (9.3 %) had EDSS of 6.5 or greater at the time of ocrelizumab initiation. Of the 113, 51 (45.1 %) were excluded: 6 (5.3 %) because they were duplicates or didn't receive ocrelizumab at our center, 25 (22.1 %) due to rituximab treatment in the previous year, 16 (14.2 %) due to lack of at least 1 year of follow up, and 4 (3.5 %) due to relevant comorbidities/treatment with other immunosuppressants. 62 patients were included in the final analysis. At ocrelizumab start, mean age was 62.1 +/- 8.7 years and median EDSS was 7.0 (range 6.5 to 9.5). Ocrelizumab was started in 26 of the included 62 patients (41.9 %) because of objective clinical disease worsening, in 17 (27.4 %) because of subjective worsening, in 8 (12.9 %) to prevent future progression. 32 patients (51.6 %) continued ocrelizumab throughout the study period, with average length of ocrelizumab use of 36.5 +/- 17.0 months. 29 patients (46.8 %) experienced no side effects during the study period. 29 (46.7 %) patients discontinued treatment, and of those, 9 (31.0 %) cited more than one reason for discontinuation: 17 (58.6 %) cited side effects, 12 (41.4 %) cited progression/lack of benefit, 6 (20.7 %) cited the Covid19 pandemic, and 1 (3.4 %) cited financial issues as a reason for discontinuation. Over the course of the study, 16 (25.8 %) patients had disability worsening by EDSS, 5 (8.1 %) had disability improvement, and 41 (66.1 %) remained stable, with a median end EDSS of 7.0 (range 6.5 to 9.5). Importantly, 18 patients (29.0 %) reported subjective disease stability while on ocrelizumab.

CONCLUSIONS:

Ocrelizumab may lead to disease stabilization in a subset of highly disabled MS patients, but possible benefits need to be carefully balanced against the incidence of adverse events in this high-risk patient population.

01 Feb 2024·Pediatric blood & cancer

Late effects in survivors of post‐transplant lymphoproliferative disease

Article

Author: Healey, Jessica M ; Hayashi, Robert J ; Sweet, Stuart ; Dharnidharka, Vikas R ; Brady, Kassidy ; Ybarra, A Marion ; McGlynn, Mary Claire ; Stoll, Janis

Abstract:

Background:

Treatment of post‐transplant lymphoproliferative disease (PTLD) varies, with only some patients receiving chemotherapy. Concern for chemotherapy toxicities may influence treatment decisions as little is known regarding the late effects (LE) in PTLD survivors. This report characterizes LE in PTLD survivors at our institution.

Procedure:

Pediatric patients (0–18 years old) diagnosed with PTLD from 1990 to 2020 were examined. All patients included survived 6 months after completing chemotherapy or were 6 months from diagnosis if received no chemotherapy. Treatment with anti‐CD20 antibody (rituximab) alone was not considered chemotherapy. Toxicities were classified per Common Terminology Criteria for Adverse Events Version 5.0. Chi‐square tests assessed differences between categorical groups, or Fischer's exact test or the Fischer–Freeman–Halton exact test for limited sample sizes.

Results:

Of the 44 patients included, 24 (55%) were treated with chemotherapy. Twenty‐four (55%) were alive at last follow‐up. Chemotherapy was not associated with differences in survival (odds ratio [OR] 1.40, confidence interval [CI]: 0.42–4.63; p = .31). All patients experienced LE. Grade 3 toxicity or higher was experienced by 82% of patients with no difference in incidence (OR 1.20, CI: 0.27–5.80; p > .99) or median toxicity grade (3.00 vs. 4.00, p = .21) between treatment groups. Patients who received chemotherapy were more likely to experience blood and lymphatic toxicity (58% vs. 25%, p = .03) and cardiac toxicity (46% vs. 15%, p = .03), but less likely to have infections (54% vs. 85%, p = .03).

Conclusions:

Survivors of PTLD experience LE including late mortality regardless of chemotherapy exposure. Further investigation to better understand LE could optimize upfront therapy for children with PTLD and improve outcomes.

News (Medical) associated with Veltuzumab

17 Apr 2024

·www.prnewswire.com

Novartis Kesimpta® six-year efficacy data show substantial benefits in recently diagnosed treatment-naïve people with relapsing multiple sclerosis

Continuous Kesimpta® treatment for up to six years showed sustained efficacy in recently diagnosed (≤3 years) treatment-naïve people living with relapsing multiple sclerosis (RMS) in an analysis of the ALITHIOS open-label extension study1 Similar efficacy outcomes were demonstrated in a separate analysis of continuous Kesimpta treatment for up to six years in the overall ALITHIOS study population2 Switch from teriflunomide to Kesimpta resulted in significant improvements across several efficacy outcomes such as annualized relapse rate and MRI lesion activity in both analyses1,2 Treatment with Kesimpta for up to six years continues to be well tolerated with consistent safety outcomes, supporting the favorable benefit-risk profile of Kesimpta in RMS2 EAST HANOVER, N.J., April 17, 2024 /PRNewswire/ -- Novartis today announced data from the ALITHIOS open-label extension study showing sustained efficacy of first-line, continuous Kesimpta® (ofatumumab) treatment for up to six years in recently diagnosed – defined as starting treatment within three years of initial diagnosis – treatment-naïve people living with relapsing multiple sclerosis (RMS).1 These efficacy outcomes included 44% fewer relapses; 96.4% and 82.7% reductions in MRI lesions (Gd+ T1 and neT2), respectively; and 24.5% and 21.6% fewer 3- and 6-month confirmed disability worsening (CDW) events, respectively, versus those who switched to Kesimpta from teriflunomide.1 A separate analysis of the overall ALITHIOS population showed similar efficacy with continuous Kesimpta treatment, which was also well-tolerated with a consistent safety profile up to six years.2 These data will be presented at the American Academy of Neurology (AAN) 2024 Annual Meeting held in Denver, Colorado and virtually on April 13-18, 2024. "Our analysis of treatment-naïve people who were recently diagnosed with relapsing multiple sclerosis found that first-line use of Kesimpta for up to six years provided long-term benefits, including fewer relapses, profoundly suppressed MRI lesion activity, and fewer disability worsening events," said principal investigator Gabriel Pardo, M.D., Founding Director of the Multiple Sclerosis Center of Excellence at Oklahoma Medical Research Foundation. "While measurable improvements were also seen in patients switching to Kesimpta later on, the delay in irreversible disability worsening was not fully realized in the switch group compared to those starting on Kesimpta first, reinforcing the value of introducing the treatment to patients earlier." "We are extremely pleased to share the new data from ALITHIOS, which adds to the growing body of evidence of Kesimpta as an efficacious and well-tolerated option for people living with RMS," said Norman Putzki, M.D., Development Unit Head, Neuroscience & Gene Therapy, Development, Novartis Pharmaceuticals Corporation. "Novartis is committed to addressing the biggest challenges for people living with MS through relentless discovery, development, and delivery of potentially transformative medicines with the goal of achieving complete disease control." Study Results In the first analysis, the low annualized relapse rate (ARR) experienced by recently diagnosed treatment-naïve (RDTN) people living with RMS receiving continuous Kesimpta during the core Phase III trials was further reduced in the ALITHIOS open-label extension study, from 0.104 to 0.050 (52.0% reduction), corresponding to an adjusted ARR of one relapse per 20 years.1 Rates of 3- and 6-month progression independent of relapse activity (PIRA) with first-line Kesimpta were also lower versus switch.1 The observed rapid increase in the proportion of participants with no evidence of disease activity (NEDA-3) with continuous first-line Kesimpta treatment was maintained up to six years.1 In RDTN people living with RMS initially randomized to teriflunomide, improvements across several efficacy outcomes were seen after switching to Kesimpta, including significant reductions in ARR (71.3%) and in MRI lesion activity (Gd+ T1: 98.5% reduction; neT2: 93% reduction), and rapid increase in rates of NEDA-3.1 However, rates of 3- and 6-month CDW events remained higher compared to patients receiving continuous Kesimpta, indicating that the efficacy benefit of first-line Kesimpta on delaying disability worsening was not fully achieved in the switch group.1 Across both continuous and switch groups, nine out of 10 participants achieved NEDA-3 at Year 6.1 Similar results were seen in the second analysis, which looked at the overall ALITHIOS population.2 Data showed sustained efficacy of continuous Kesimpta up to six years, including low ARR (49.9% reduction between core Phase III trials and extension phase), suppression of MRI lesion activity (Gd+ T1: 56.7% reduction; neT2: 89.3% reduction), sustained reduction of 6-month CDW events (14.1%, relative to the switch group), lower rates of 6-month PIRA, and sustained high rates of NEDA-3.2 People switching from teriflunomide to Kesimpta experienced reductions in ARR (73.8%) and MRI lesion activity (Gd+ T1: 97.7% reduction; neT2: 91.8% reduction) and a rapid increase in NEDA-3 rates during the extension period.2 Six-month CDW rates remained higher compared to patients receiving continuous Kesimpta, again highlighting an efficacy benefit of first-line Kesimpta on delaying disability worsening that was not fully achieved in the switch group.2 At Year 6, NEDA-3 status was achieved in nine out of 10 participants in both the continuous and switch groups.2 The study also found that treatment with Kesimpta for up to six years was well-tolerated with no unexpected safety signals identified.2 The rates of adverse events (AEs), serious AEs, serious infections, and malignancies remained stable with no increased risks over six years.2 The overall rates of AEs and serious AEs up to six years of Kesimpta treatment were consistent between the core Phase III trials and the ALITHIOS extension study.2 The most common AEs were infections (COVID-19 [34.3%], nasopharyngitis [20.6%], upper respiratory tract infection [14.9%], and urinary tract infection [14.4%]).2 The incidence of serious infections remained stable over time and did not increase with Kesimpta treatment up to six years.2 Mean serum immunoglobulin G (IgG) levels remained stable up to six years of treatment and the majority of patients (97.2%) had lgG levels above the lower limit of normal (LLN).2 Mean serum immunoglobulin M (IgM) levels decreased over time but remained above the LLN for the majority of patients (65.9%).2 No clinically meaningful association was observed between IgG/IgM levels below the LLN and risk of serious infections.2 About Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by myelin destruction and axonal damage in the brain, optic nerves and spinal cord.3 MS, which affects around 2 million people worldwide, can be characterized into four main types: clinically isolated syndrome (CIS), relapsing-remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS).4,5 The various forms of MS can be distinguished based on whether a patient experiences relapses (clearly defined acute inflammatory attacks of worsening neurological function), and/or whether they experience progression of neurologic damage and disability from the onset of the disease.3 About Kesimpta® (ofatumumab) Kesimpta is a targeted, precisely dosed and delivered B-cell therapy that provides the flexibility of self-administration for adults with relapsing forms of multiple sclerosis (RMS). Kesimpta is the first fully human anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly injection, delivered subcutaneously (SC) in RMS.6, 7, 8 The treatment regimen was designed and tested to enhance safety and tolerability and minimize the risk of systemic injection-related reactions.6 Initial doses of Kesimpta are at Weeks 0, 1 and 2, with the first injection performed under the guidance of a healthcare professional. Monthly Kesimpta 20 mg doses are associated with rapid reduction and near-complete peripheral B-cell depletion, with no significant effect on pharmacokinetics due to body weight.6 As shown in preclinical studies, Kesimpta is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion.9 The selective mechanism of action and SC administration of Kesimpta allows precise delivery to the lymph nodes, where B-cell depletion in MS is needed, and preclinical studies have shown that it may preserve the B-cells in the spleen.10 Data from the ASCLEPIOS I/II core studies demonstrate Kesimpta's efficacy and favorable safety and tolerability profile in RMS participants and the ALITHIOS open-label extension study provides additional support with up to 6 years of data.2,11 The at-home administration of Kesimpta by monthly doses of 20 mg/0.4mL with an autoinjector (Sensoready®) also matches the preferences of many people living with MS due to its ease of use and supports patients to be compliant with, and persistent on the therapy over time.6 Kesimpta was originally developed by Genmab and licensed to GlaxoSmithKline; Novartis obtained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, in December 2015.12 Kesimpta has been approved for the treatment of relapsing forms of multiple sclerosis in over 90 countries worldwide with more than 100,000 patients treated as of March 2024. Novartis in Neuroscience At Novartis, in Neuroscience, we are committed to understanding and solving some of the most burdensome neurological conditions to improve the quality of life for patients and their caregivers, and to make a positive impact on society. We aim to lead the discovery, development and delivery of innovative medicines to create a transformational impact for people living with severe neurological conditions by changing the course of disease progression. Through innovation, partnerships and community engagement, we have been tackling neurological conditions for >80 years, launching transformative treatments which have made meaningful differences to millions of people worldwide. We continue to collaborate on the development of industry-leading innovative medicines for multiple sclerosis, and in the areas of neuroimmunology, neurodegeneration, and neuromuscular/rare diseases. To ensure patients everywhere can benefit from these life-changing therapies, we work closely with key stakeholders across the world to ensure rapid access and sustainable accessibility to our medicines, with the aim of providing the best treatment choices for each person's unique journey. KESIMPTA Indication KESIMPTA is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS) including clinically isolated syndrome (CIS), relapsing-remitting disease, and active secondary progressive disease. It is not known if KESIMPTA is safe or effective in children. Important Safety Information Who should not take KESIMPTA? Do NOT take KESIMPTA if you: have an active hepatitis B virus (HBV) infection. have had an allergic reaction to ofatumumab or life-threatening injection-related reaction to KESIMPTA. What is the most important information I should know about KESIMPTA? KESIMPTA can cause serious side effects such as: Infections. Serious infections, which can be life-threatening or cause death, can happen during treatment with KESIMPTA. If you have an active infection, your health care provider (HCP) should delay your treatment with KESIMPTA until your infection is gone. KESIMPTA taken before or after other medicines that weaken the immune system may increase your risk of getting infections. Tell your HCP right away if you have any infections or get any symptoms including painful and frequent urination, nasal congestion, runny nose, sore throat, fever, chills, cough, or body aches. HBV reactivation. If you have ever had HBV infection, it may become active again during or after treatment with KESIMPTA (reactivation). If this happens, it may cause serious liver problems including liver failure or death. Before starting KESIMPTA, your HCP will do a blood test to check for HBV. They will also continue to monitor you during and after treatment with KESIMPTA for HBV. Tell your HCP right away if you get worsening tiredness or yellowing of your skin or the white part of your eyes. Progressive Multifocal Leukoencephalopathy (PML). PML may happen with KESIMPTA. PML is a rare, serious brain infection caused by a virus that may get worse over days or weeks. PML can result in death or severe disability. Tell your HCP right away if you have any new or worsening neurologic signs or symptoms. These may include weakness on one side of your body, loss of coordination in arms and legs, vision problems, changes in thinking and memory, which may lead to confusion and personality changes. Weakened immune system. KESIMPTA taken before or after other medicines that weaken the immune system could increase your risk of getting infections. Before you take KESIMPTA, tell your HCP about all your medical conditions, including if you: Have or think you have an infection including HBV or PML. Have ever taken, currently take, or plan to take medicines that affect your immune system. These medicines could increase your risk of getting an infection. Have had a recent vaccination or are scheduled to receive any vaccinations. You should receive any required 'live' or 'live-attenuated' vaccines at least 4 weeks before you start treatment with KESIMPTA. You should not receive 'live' or 'live-attenuated' vaccines while you are being treated with KESIMPTA and until your HCP tells you that your immune system is no longer weakened. Whenever possible, you should receive any 'non-live' vaccines at least 2 weeks before you start treatment with KESIMPTA. Talk to your HCP about vaccinations for your baby if you used KESIMPTA during your pregnancy. Are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if KESIMPTA will harm your unborn baby. Females who can become pregnant should use birth control (contraception) during treatment with KESIMPTA and for 6 months after your last treatment. Talk with your HCP about what birth control method is right for you during this time. Are breastfeeding or plan to breastfeed. It is not known if KESIMPTA passes into your breast milk. Talk to your HCP about the best way to feed your baby if you take KESIMPTA. Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should I use KESIMPTA? See the detailed Instructions for Use that comes with KESIMPTA for information about how to prepare and inject a dose of KESIMPTA and how to properly throw away (dispose of) used KESIMPTA Sensoready pens or prefilled syringes. Use KESIMPTA exactly as your HCP tells you to use it. Your HCP will show you how to prepare and inject KESIMPTA the right way before you use it for the first time. Do not inject into areas where the skin is tender, bruised, red, scaly or hard. Avoid areas with moles, scars, or stretch marks. KESIMPTA may cause serious side effects including: Injection-related reactions. Injection-related reactions are a common side effect of KESIMPTA. Injecting KESIMPTA can cause injection-related reactions that can happen within 24 hours (1 day) following the first injections and with later injections. There are two kinds of reactions: at or near the injection site: redness of the skin, swelling, itching, and pain. Talk to your HCP if you have any of these signs and symptoms. that may happen when certain substances are released in your body: fever, headache, pain in the muscles, chills, tiredness, rash, hives, trouble breathing, swelling of the face, eyelids, lips, mouth, tongue and throat, and feeling faint, or chest tightness. Contact your HCP right away if you experience any of these signs and symptoms, especially if they become worse or you have new severe signs of reactions after subsequent injections. It could be a sign of an allergic reaction, which can be serious. Low immunoglobulins. KESIMPTA may cause a decrease in some types of antibodies. Your HCP will do blood tests to check your blood immunoglobulin levels. The most common side effects of KESIMPTA include: Upper respiratory tract infection, with symptoms such as sore throat and runny nose, and headache. Headache. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please see full Prescribing Information including Medication Guide. Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at and and connect with us on LinkedIn, LinkedIn US, Facebook, X/Twitter, X/Twitter US and Instagram. References Pardo G, Hauser SL, Bar-Or A, et al. Longer-term (up to 6 Years) Efficacy of Ofatumumab in People with Recently Diagnosed and Treatment-Naïve Relapsing Multiple Sclerosis. Oral presentation at the American Academy of Neurology (AAN) 2024 Annual Meeting; April 13-18, 2024; Denver, CO. Wiendl H, Hauser SL, Nicholas J, et al. Longer-term Safety and Efficacy of Ofatumumab in People With Relapsing Multiple Sclerosis for Up to 6 Years. Poster presentation at the American Academy of Neurology (AAN) 2024 Annual Meeting; April 13-18, 2024; Denver, CO. Guthrie EW. Multiple sclerosis: A primer and update. Adv Studies Pharm. 2007;4(11):313-317. Multiple Sclerosis International Federation. Atlas of MS 2013-Mapping Multiple Sclerosis Around the World. Accessed August 12, 2020. National MS Society. Types of MS. Accessed January 18, 2023. Hauser SL, Kappos L, Bar-Or A, et al. The Development of Ofatumumab, a Fully Human Anti-CD20 Monoclonal Antibody for Practical Use in Relapsing Multiple Sclerosis Treatment. Neurol Ther. 2023;12(5):1491-1515. doi:10.1007/s40120-023-00518-0 Kesimpta Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; September 2022. Bar-Or A, Fox E, Goodyear A, et al. Onset of B-cell depletion with subcutaneous administration of ofatumumab in relapsing multiple sclerosis: results from the APLIOS bioequivalence study. Poster presentation at: ACTRIMS; February 2020; West Palm Beach, FL. Smith P, Kakarieka A, Wallstroem E. Ofatumumab is a fully human anti-CD20 antibody achieving potent B-cell depletion through binding a distinct epitope. Poster presentation at: ECTRIMS; September 2016; London, UK. Smith P, Huck C, Wegert V, et al. Low-dose, subcutaneous anti-CD20 therapy effectively depletes B-cells and ameliorates CNS autoimmunity. Poster presentation at: ECTRIMS; September 2016; London, UK. Cohen, JA, Hauser SL, Zielman R., et al. Effect of Longer-term Ofatumumab Treatment on Disability Progression and Brain Volume Change. Poster presentation at: AAN; April 2023; Boston, US. Genmab Press Release: Genmab announces completion of agreement to transfer remaining ofatumumab rights. December 21, 2015. Accessed January 18, 2023. # # # SOURCE Novartis Pharmaceuticals Corporation

Clinical ResultPhase 3Drug Approval

04 Apr 2024

·www.prnewswire.com

IASO Bio Announces U.S. FDA Approval of Investigational New Drug Application for BCMA CAR-T Equecabtagene Autoleucel for Generalized Myasthenia Gravis

SHANGHAI, NANJING, China and SAN JOSE, Calif., April 4, 2024 /PRNewswire/ -- IASO Biotechnology ("IASO Bio"), a biopharmaceutical company dedicated to discovering, developing, manufacturing and commercialising innovative cell therapy and antibody products, is pleased to announce that the Investigational New Drug (IND) application for its BCMA CAR-T (Equecabtagene Autoleucel) has been approved by the U.S. Food and Drug Administration (FDA) for use in U.S. clinical trials for generalised myasthenia gravis (gMG). The Chinese IND for this indication of Equecabtagene Autoleucel was approved by the NMPA in January this year. Two subjects with refractory MG were enrolled in an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557 One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK-IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the doses of 1.0×106 CAR-T/Kg, respectively. Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. Eff icacy : Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS). No immunomodulatory therapy other than low dose pyridostigmine (90 mg/day and 60 mg/day, respectively) was used during the follow-up period. PK/PD: Eque-cel expanded well after infusion. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually. At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. About MG Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder. The main clinical manifestation of MG is a decrease in muscle strength in local or systemic muscles, which can affect eye, respiratory and limb muscles and other important muscle groups, which has a huge negative impact on the patient's quality of life, and dysphagia or breathing difficulty caused by a myasthenic crisis can be life-threatening. The main pathogenic antibodies in MG include AChR, MuSK and LRP4 antibodies. A very small number of patients have no detectable antibodies in their serum1. MG can occur at any age and is slightly more common in women than in men 2. According to relevant studies, the incidence rate of MG in the United States is 3.1/100,000 people and the prevalence rate is 37.0/100,000 people3. It is estimated that the number of people with MG incidence in the United States in 2023 was more than 10,000, and the number of patients with MG was about 124,000. Ms. Jinhua Zhang, Founder, Chairman, and Chief Executive Officer of IASO Bio, stated, "We are very pleased that Equecabtagene Autoleucel has been approved for clinical trial for myasthenia gravis in the United States. This is the result of the unremitting efforts of our team and is an important milestone in our efforts to improve the quality of life of patients with autoimmune diseases around the world. We will actively obtain more data on the safety and efficacy of Equecabtagene Autoleucel in the treatment of MG patients, and better explore and define the significance of this innovative cell therapy in the treatment of immune diseases. We hope Equecabtagene Autoleucel will provide a more efficient and long-lasting therapeutic option for myasthenia gravis and potentially other autoimmune diseases." About IASO Bio IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production. The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of R/RMM. Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit or . SOURCE IASO Bio

Cell TherapyImmunotherapyDrug ApprovalClinical ResultClinical Study

29 Feb 2024

·www.prnewswire.com

IASO Bio's Equecabtagene Autoleucel for Refractory Myasthenia Gravis (MG) Case Report Published in EMBO Molecular Medicine

SHANGHAI and NANJING, China and SAN JOSE, Calif., Feb. 29, 2024 /PRNewswire/ -- On February 26, 2024, the impactful international academic journal, EMBO Molecular Medicine, published the clinical data of the fully human BCMA targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, CT103A) for the treatment of two refractory myasthenia gravis (MG) subjects. B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis, initially demonstrated the good tolerability and safety of Eque-cel in the treatment of MG, as well as the durable clinical efficacy. MG is an autoimmune disease with acquired neuromuscular junction (NMJ) transmission disorders mediated by antibodies. Antibodies to the Acetylcholine Receptor (AChR) are the most common pathogenic antibodies; in addition, antibodies such as Muscle-Specific receptor tyrosine Kinase (MuSK), low-density Lipoprotein Receptor-related Protein 4 (LRP4), and Ryanodine Receptor (RyR), have also been found to be involved in the pathogenesis of MG. Currently, the treatment of MG is still based on cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulin, plasma exchange, and thymectomy. The main causes of death in MG patients include respiratory failure and pulmonary infections. This is an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557). It was conducted by Prof. Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Two subjects with refractory MG were enrolled in this study. One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK- IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the doses of 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg， respectively. Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. Effectiveness: Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS). No immunomodulatory therapy other than low dose pyridostigmine (90 mg/day and 60 mg/day, respectively) was used during the follow-up period. PK/PD: Eque-cel expanded well after infusion and persisted for a shorter period than that in multiple myeloma patients. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually. At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. The principal investigator of this study, Prof. Wei Wang of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, said "Myasthenia Gravis has a long course, is difficult to cure, and is prone to recurrence. Current treatment with traditional medications, although is able to improve symptoms of Myasthenia Gravis to a certain extent, is deficient in terms of disease control and long-term safety, and there is an urgent need for patients to have a better clinical outcome and treatment modality. In our study, it is gratifying to see that BCMA CAR-T cell therapy can prevent MG disease progression and show signs of reversal of the disease, which is expected to change the MG treatment landscape and bring hope for a cure to patients." In addition to the results of this published study, IASO Bio and a team of investigators continue to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other antibody-mediated autoimmune diseases, including optic neuromyelitis optica spectrum disorders (NMOSD), Immune-Mediated Necrotizing Myelopathy (IMNM), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with an aim to change the landscape of treatment for autoimmune diseases. About IASO Bio IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production. The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of RRMM. Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit or . SOURCE IASO Bio

Clinical ResultClinical StudyImmunotherapyCell TherapyDrug Approval

100 Deals associated with Veltuzumab

External Link

KEGG	Wiki	ATC	Drug Bank
D09031	Veltuzumab	-	DB05656

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Phase 2	US	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	AR	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	CA	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	CZ	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	DE	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	HU	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	IT	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	MX	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	PL	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011
Rheumatoid Arthritis	Phase 2	ES	Takeda Pharmaceutical Co., Ltd.	01 Aug 2011

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ECTRIMS2023	Not Applicable	Multiple Sclerosis, Relapsing-Remitting	-	anti-CD20 monoclonal antibody	wnbefzdmcj(vypxjcvccp) = nfptgavduw epueywrszf (vqwdvlxaus )	Positive	30 Sep 2023
				anti-CD20 monoclonal antibody	wnbefzdmcj(vypxjcvccp) = ymefqkvcpz epueywrszf (vqwdvlxaus )
ECTRIMS2022	Not Applicable	Multiple Sclerosis, Relapsing-Remitting CD20	-	Anti-CD20 mAb treated patients with RRMS	skaqenosvc(wexnmoamtn) = kpwkyiejjr gcutbhjcrq (kvncvbxwgg ) View more	-	12 Oct 2022
				anti-CD20 monoclonal antibody	skaqenosvc(wexnmoamtn) = rlobifbnkh gcutbhjcrq (kvncvbxwgg ) View more
ACTRIMS2020	Not Applicable	-	-	anti-CD20 monoclonal antibody	npkimayiua(ugudakgatd) = uzofxplfqf qlwurvmupz (fdvrpevuux ) View more	-	11 May 2020
				anti-CD20 monoclonal antibody	npkimayiua(ugudakgatd) = vwnubjuvwy qlwurvmupz (fdvrpevuux ) View more
FP208 (ERA2019)	Not Applicable	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis	242	Mabthera	pwhocrwtfw(ehawjrukup) = One episode of anaphylaxis was reported with Mabthera jjmgerhnpu (xzjgxnybdt ) View more	Positive	13 Jun 2019
				Truxima
NCT00547066 (Pubmed \| Haematologica) Manual	Phase 1/2	Purpura, Thrombocytopenic, Idiopathic CD20 Positive	50	Veltuzumab	ytnoywrtks(uyxdrdnpen) = transient，mild to moderate ccvmbykxpe (rjtrqppjde )	Positive	01 Nov 2016
NCT00546793 (Pubmed \| Leuk Lymphoma) Manual	Phase 1	Chronic Lymphocytic Leukemia	21	veltuzumab	oddedxotnw(xjysavjbgi) = rahthxfiea fsnejwokrn (omupwqgzow ) View more	Positive	01 Jan 2016
NCT00989586 (Pubmed \| Br J Haematol) Manual	Phase 1/2	B-Cell Lymphoma	35	milatuzumab+veltuzumab	ouxmyxjyxm(etiurcukhx) = acfxtnhmko zwjsiizhra (iwcmqgstds ) View more	Positive	01 Jun 2015
				Veltuzumab 200 mg/m(2) weekly + Milatuzumab 16 mg/kg weekly	-
NCT00546793 (Pubmed \| Haematologica)	Phase 1/2	Indolent Non-Hodgkin Lymphoma	17	80 mg veltuzumab	zvzrnqnnzp(dqfwxrqanu) = oxaidiguak lfwworcret (ukachmdvkg ) View more	Positive	01 Apr 2011
				160 mg veltuzumab	zvzrnqnnzp(dqfwxrqanu) = gxlcvoccrq lfwworcret (ukachmdvkg )
NCT00285428 \| NCT00596804 (Pubmed \| J Urol)	Phase 1/2	Recurrent Non-Hodgkin Lymphoma	-	Veltuzumab	fteoewafeg(qnjfuwtouh) = mtwstgores amolccmjqp (uvshrwcrxz ) View more	Positive	10 Jul 2009

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis