Delving into the Latest Updates on Ublituximab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Rituximab biobetter, Rituximab biobetter - TG Therapeutics, Ublituximab (USAN/INN)

+ [10]

Target

CD20

Mechanism

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

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases+ [2]

Active Indication

Multiple sclerosis relapseChronic lymphocytic leukaemia refractoryMantle-Cell Lymphoma+ [1]

Inactive Indication

Follicular LymphomaMarginal Zone B-Cell LymphomaNeuromyelitis Optica+ [5]

Originator Organization

rEVO Biologics, Inc.LFB Biotechnologies SASU

Active Organization

TG Therapeutics, Inc.

AstraZeneca PLC

Ildong Pharmaceutical Co., Ltd.

+ [1]

Inactive Organization

Laboratoire Français du Fractionnement et des Biotechnologies

The Johns Hopkins University

Drug Highest PhaseApproved

First Approval Date

US (28 Dec 2022),

Multiple sclerosis relapse

RegulationOrphan Drug (US)

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Gene Sequence

Sequence Code 15059H

Source: *****

Sequence Code 4724843L

Source: *****

This phase I trial studies the safety and how effective the combination of ublituximab, umbralisib, and lenalidomide is in certain types of indolent (slow-growing) non-Hodgkin's lymphoma or mantle cell lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Umbralisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Ublituximab is an antibody that attaches to the lymphoma cells and triggers immune reactions that may result in the death of the targeted lymphoma cells.

Start Date30 Sep 2022

Sponsor / Collaborator-

NCT04692155 / TerminatedPhase 1/2IIT

Phase Ib/II Trial of Ublituximab and Umbralisib With CHOP (U2-CHOP) Followed by U2 Maintenance (U2-CHOP-U2) in Previously Untreated Mantle Cell Lymphoma (MCL)

This is a single arm, multi-center, open label Phase Ib/II trial in adult patients with newly diagnosed Mantle Cell Lymphoma (MCL)(Stage II-IV). The Diagnosis of MCL (Stage II, III, IV) is supported by histology and over expression of cyclin D1 or by FISH (fluorescent in situ hybridization). In the proposed study, the primary endpoint is to estimate the biological response rate of the combination of Umbralisib at dose 800 mg with Ublituximab (900mg)-Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP), but a phase Ib portion with dose de-escalation at two does level (800 and 600 mg) will be built in to further confirm its safety and tolerability. Treatment will be administered on an outpatient basis in 3-week (21 day) cycles. Once Umbralisib dose is defined in phase Ib, the study will expand to phase II portion after SMC/DSMB (Safety monitoring committee/Data Safety Monitoring Committee) agreement.

Start Date31 Aug 2021

Sponsor / Collaborator

The University of Alabama at Birmingham

100 Clinical Results associated with Ublituximab

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100 Translational Medicine associated with Ublituximab

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100 Patents (Medical) associated with Ublituximab

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69

Literatures (Medical) associated with Ublituximab

01 Feb 2024·Multiple sclerosis and related disorders

Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis

Review

Author: Kang, Angray S ; Giovannoni, Gavin ; Baker, David ; Schmierer, Klaus

Neutropenia serves as a risk factor for severe infection and is a consequence of some immune-depleting immunotherapies. This occurs in people with multiple sclerosis following chemotherapy-conditioning in haematopoietic stem cell transplantation and potent B cell targeting agents. Whilst CD52 is expressed by neutrophils and may contribute to early-onset neutropenia following alemtuzumab treatment, deoxycytidine kinase and CD20 antigen required for activity of cladribine tablets, off-label rituximab, ocrelizumab, ofatumumab and ublituximab are not or only weakly expressed by neutrophils. Therefore, alternative explanations are needed for the rare occurrence of early and late-onset neutropenia following such treatments. This probably occurs due to alterations in the balance of granulopoiesis and neutrophil removal. Neutrophils are short-lived, and their removal may be influenced by drug-associated infections, the killing mechanisms of the therapies and amplified by immune dyscrasia due to influences on neutropoiesis following growth factor rerouting for B cell recovery and cytokine deficits following lymphocyte depletion. This highlights the small but evident neutropenia risks following sustained B cell depletion with some treatments.

23 Jan 2024·Blood advances

Response-adapted, time-limited venetoclax, umbralisib, and ublituximab for relapsed/refractory chronic lymphocytic leukemia

Article

Author: Mulford, Deborah A ; Zent, Clive S ; Liesveld, Jane L ; Gordan, Leo ; Barr, Paul M ; Winter, Allison ; Wallace, Danielle S ; Ma, Shuo ; Hill, Brian T ; Friedberg, Jonathan W ; Miskin, Hari P ; Karmali, Reem ; Sportelli, Peter ; Winter, Jane ; Baran, Andrea M ; Rowland, Chris ; Weiss, Michael S ; Bui, Andrew ; Advani, Anjali

Abstract:

Many patients with chronic lymphocytic leukemia (CLL) will develop treatment resistance to Bruton tyrosine kinase (BTK) inhibitors. Phosphatidylinositol-3-kinase (PI3K) inhibitors, including umbralisib, have significant clinical activity in relapsed/refractory CLL, but prolonged exposure is associated with potential toxicities. Owing to the synergistic antitumor effects of combined PI3K and BCL-2 inhibition, we sought to explore the feasibility of response-adapted, time-limited therapy to optimize disease control while mitigating the risks of prolonged treatment. We conducted a phase 1/2 clinical trial to determine the safety and efficacy of venetoclax in combination with umbralisib and the anti-CD20 monoclonal antibody, ublituximab, (U2-VeN) in patients with relapsed/refractory CLL (N = 46) and Richter transformation (N = 5). After 12 cycles, treatment was stopped for patients with CLL who achieved undetectable minimal residual disease (uMRD). Adverse events of special interest included diarrhea in 50% of patients (11% grade 3/4), and aspartate aminotransferase and/or alanine aminotransferase elevation in 15 patients (33%), with 3 (7%) grade 3/4. There were no cases of tumor lysis syndrome related to venetoclax, with outpatient initiation in 96% of patients. The intent-to-treat overall response rate for CLL was 98% with best response of 100% in evaluable patients (42% complete responses). The end-of-treatment rate of uMRD at 10−4 in bone marrow was 77% (30/39), including a 71% uMRD rate among 14 patients refractory to prior BTK inhibitor. Time-limited venetoclax and U2 is safe and highly effective combination therapy for patients with relapsed/refractory CLL including those who have been previously treated with covalent BTK inhibitors. This trial was registered on www.clinicaltrials.gov as #NCT03379051.

02 Dec 2023·Expert review of neurotherapeutics

Ublituximab-xiiy as a treatment option for relapsing multiple sclerosis

Review

Author: Zivadinov, Robert ; Jakimovski, Dejan ; Weinstock-Guttman, Bianca

INTRODUCTION:

B cell depletion has been established as an efficacious anti-inflammatory therapy in people with relapsing forms of multiple sclerosis (MS). Ublituximab (ublituximab-xiiy) is the latest approved chimeric glycoengineered anti-CD20 monoclonal antibody (mAb) for the treatment of relapsing forms of MS.

AREAS COVERED:

In this narrative review, the authors explore the safety and effectiveness of data derived from the Phase 2 and Phase 3 ublituximab trials and from their respective post-hoc analyses. Moreover, they consider the similarities and differences between the currently available anti-CD20 antibodies for treatment of relapsing MS. Lastly, the authors discuss the role and place of ublituximab in the current disease modifying therapy landscape.

EXPERT OPINION:

Ublituximab is a rapid-acting and effective anti-inflammatory option as a treatment in people with relapsing MS that significantly reduced the annualized relapse rate and MRI-based disease activity. When compared to the Phase III trials of the other two anti-CD20 mAbs (ocrelizumab and ofatumumab), ublituximab did not result with reduction of 3 or 6-month confirmed disability progression. These differences may be attributed to the overall low rate of progression in both the ublituximab and the active comparator teriflunomide arm. Future data from open-label extensions are warranted. There was no significant reduction of ublituximab on whole-brain atrophy compared to teriflunomide.

129

News (Medical) associated with Ublituximab

25 Jun 2024

·firstwordpharma.com

EU greenlights subcutaneous version of Roche’s Ocrevus to treat multiple sclerosis

The European Commission approved the subcutaneous (SC) formulation of Roche’s Ocrevus (ocrelizumab) to treat relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), maintaining the same twice-yearly dosing schedule as the intravenous (IV) version. The company noted Tuesday that the new formulation is intended to be administered by healthcare providers, either in the clinic or in other settings.“Now, people in the EU with multiple sclerosis can have their medicine administered in just 10 minutes twice per year without needing an IV facility,” making “it easier for more people…to access their treatment, while also saving time for providers,” said Levi Garraway, chief medical officer at Roche.The approval was backed by findings from the Phase III OCARINA II study, which showed that SC Ocrevus resulted in non-inferior blood levels, alongside a comparable safety and efficacy profile to the IV formulation. Moreover, over 92% of study participants surveyed reported being satisfied or very satisfied with the SC formulation.The SC version of the anti-CD20 antibody, which uses Halozyme's Enhanze drug delivery technology, is also awaiting a decision by the FDA in September. In a Firstword poll of US neurologists conducted last year, nearly a third of respondents said they would use SC Ocrevus exclusively over the IV version if approved, and half of those surveyed believed the Ocrevus franchise would gain a significant advantage over other anti-CD20 competitors such as Novartis’ Kesimpta (ofatumumab) and TG Therapeutics’ Briumvi (ublituximab).Ocrevus remains Roche’s top-selling drug, racking up CHF 6.4 billion ($7.1 billion) in global sales last year, with the EU accounting for nearly CHF 1.1 billion ($1.2 billion) of it.

Phase 3Clinical ResultDrug Approval

07 Jun 2024

·www.globenewswire.com

TG Therapeutics to Participate in the Goldman Sachs 45th Annual Global Healthcare Conference

Fireside chat scheduled for Tuesday, June 11, 2024, at 1:20 PM ETNEW YORK, June 07, 2024 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX) today announced that Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, will participate in the Goldman Sachs 45th Annual Global Healthcare Conference, being held at the Loews Miami Beach Hotel, Miami Beach, FL on June 10-13, 2024. The fireside chat is scheduled to take place on Tuesday, June 11, 2024, at 1:20 PM ET. A live webcast of the fireside chat will be available on the Events page, located within the Investors & Media section, of the Company’s website at http://ir.tgtherapeutics.com/events. ABOUT TG THERAPEUTICSTG Therapeutics is a fully integrated, commercial stage, biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell diseases. In addition to a research pipeline including several investigational medicines, TG has received U.S. Food and Drug Administration (FDA) approval for BRIUMVI® (ublituximab-xiiy), for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, as well as approval by the European Commission (EC) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for BRIUMVI to treat adult patients with RMS who have active disease defined by clinical or imaging features in Europe and the United Kingdom, respectively. For more information, visit www.tgtherapeutics.com, and follow us on X (formerly Twitter) @TGTherapeutics and on LinkedIn. BRIUMVI® is a registered trademark of TG Therapeutics, Inc. CONTACT: Investor RelationsEmail: ir@tgtxinc.comTelephone: 1.877.575.TGTX (8489), Option 4 Media Relations:Email: media@tgtxinc.comTelephone: 1.877.575.TGTX (8489), Option 6

Drug Approval

07 Jun 2024

·www.biospace.com

TG Therapeutics to Participate in the Goldman Sachs 45th Annual Global Healthcare ConferenceFireside chat scheduled for Tuesday, June 11, 2024, at 1:20 PM ET

NEW YORK, June 07, 2024 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX) today announced that Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, will participate in the Goldman Sachs 45th Annual Global Healthcare Conference, being held at the Loews Miami Beach Hotel, Miami Beach, FL on June 10-13, 2024. The fireside chat is scheduled to take place on Tuesday, June 11, 2024, at 1:20 PM ET. A live webcast of the fireside chat will be available on the Events page, located within the Investors & Media section, of the Company’s website at . ABOUT TG THERAPEUTICS TG Therapeutics is a fully integrated, commercial stage, biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell diseases. In addition to a research pipeline including several investigational medicines, TG has received U.S. Food and Drug Administration (FDA) approval for BRIUMVI® (ublituximab-xiiy), for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, as well as approval by the European Commission (EC) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for BRIUMVI to treat adult patients with RMS who have active disease defined by clinical or imaging features in Europe and the United Kingdom, respectively. For more information, visit and follow us on X (formerly Twitter) @TGTherapeutics and on LinkedIn. BRIUMVI® is a registered trademark of TG Therapeutics, Inc. CONTACT: Investor Relations Email: ir@tgtxinc.com Telephone: 1.877.575.TGTX (8489), Option 4 Media Relations: Email: media@tgtxinc.com Telephone: 1.877.575.TGTX (8489), Option 6

Drug Approval

100 Deals associated with Ublituximab

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KEGG	Wiki	ATC	Drug Bank
D11243	Ublituximab	-	DB11850

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Multiple sclerosis relapse	US	TG Therapeutics, Inc.	28 Dec 2022

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	Phase 3	US	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	AU	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	IL	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	IT	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	PL	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	SK	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	KR	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	ES	TG Therapeutics, Inc.	25 May 2016
Diffuse Large B-Cell Lymphoma	Phase 3	GB	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	US	TG Therapeutics, Inc.	25 May 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02612311 (CTgov)	Phase 3	Chronic Lymphocytic Leukemia	603	Ublituximab+Umbralisib (Experimental: Arm A: Ublituximab + Umbralisib)	wnnfumwhid(ojdcxuymjt) = atslyfonhu letwjzvbem (lktsfowhoh, lxpdgdlqbv - yotmixsbzt) View more	-	07 May 2024
				Obinutuzumab+Chlorambucil (Active Comparator: Arm B: Obinutuzumab + Chlorambucil)	wnnfumwhid(ojdcxuymjt) = kksznjyrfq letwjzvbem (lktsfowhoh, kivfxvivpf - wrongkbqjn) View more
NCT03801525 (ULTRA-V, CTgov)	Phase 2/3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	277	Ublituximab+Venetoclax+Umbralisib (Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V))	qcazydionl(dygrmrnzdq) = pwcfssvavd qcrrkxiibj (ejijndvrwq, quyfhtnogf - enszmoxzax) View more	-	19 Apr 2024
				Ublituximab+Venetoclax+Umbralisib (Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V))	yzgorpzfjy(myfbzmmriz) = oddyrctdiw xmteazoilq (zdllrhyaih, xynwyrmgyf - jinfkyvppp) View more
NCT05877963 (ENHANCE, ACTRIMS2024) Manual	Phase 3	Multiple sclerosis relapse	-	Ublituximab 450 mg infusion, 2 hr	rkdpdhuuds(seuzccdbtr) = lygquhqygl gwwfnxvlrh (uyelzvytcj )	Positive	29 Feb 2024
				Ublituximab 450 mg infusion, 1 hr	rkdpdhuuds(seuzccdbtr) = ecamkcyxyj gwwfnxvlrh (uyelzvytcj )
NCT04508647 (CTgov)	Phase 2	Follicular Lymphoma \| Marginal Zone B-Cell Lymphoma	4	Ublituximab (Ublituximab Only)	mesrrpdwkj(fxojqcqtab) = zaguzsbtjc xjobgozcgg (unemsnjisl, mtorokpbnu - eznupisjxx) View more	-	09 Nov 2023
				Ublituximab+Umbralisib (Ublituximab First, Then Ublituximab and Umbralisib)	mesrrpdwkj(fnqmvvjwag) = wzedqjvwfd wetevqgzmi (tvtgtorwvm, pqpdhehfwt - qhelezaijn) View more
ULTIMATE I & II (ECTRIMS2023)	Phase 3	CD20	-	Ublituximab 450 mg	wcaelyymrs(dpydcdptln) = jdyfmndxqh ivcugkcjbe (jlrwawrkvx, -0.82 to 13.46) View more	Positive	30 Sep 2023
				Teriflunomide 14 mg	wcaelyymrs(dpydcdptln) = riandxptkk ivcugkcjbe (jlrwawrkvx, 17.77 - 31.96) View more
NCT04692155 (CTgov)	Phase 1/2	Mantle-Cell Lymphoma	1	Ublituximab+Umbralisib	shsmqitqxs(kvvayjimwu) = fwnzdeoszp eemvwxevte (mszizokfch, hexbkmuqdl - yraatwoqee) View more	-	28 Sep 2023
NCT04016805 (CTgov)	Phase 2	Chronic Lymphocytic Leukemia	41	Ibrutinib+Ublituximab+Umbralisib (Ublituximab + Umbralisib + Ibrutinib)	nkjsawhxkp(qihqqxzlyt) = iitpeyshak dvupfazatu (bexqroxkms, haljpryhrq - jnxtivqave) View more	-	24 Jul 2023
				Ublituximab+Venetoclax+Umbralisib (Ublituximab + Umbralisib + Venetoclax)	nkjsawhxkp(qihqqxzlyt) = steietyrvd dvupfazatu (bexqroxkms, omkuihhrua - ncfoousoar) View more
NCT03828448 (CTgov)	Phase 2	Small Lymphocytic Lymphoma \| Follicular Lymphoma	34	Ublituximab+Umbralisib	htfymkejkq(hfciwrdlvp) = nglgfzvfxo lmdsgrmhsa (teaqzdcdrk, ivlmxvmjhb - jwpnefougw) View more	-	24 Jul 2023
EMA Manual	Not Applicable	Multiple Sclerosis, Relapsing-Remitting	1,089	Ublituximab (ULTIMATE I)	accdfodltz(jveurmjaib) = qcqwcndzvg fzzmjymbln (hokrwqdlnf ) View more	Positive	13 Jul 2023
				Teriflunomide (ULTIMATE I)	accdfodltz(jveurmjaib) = qiigdlwibm fzzmjymbln (hokrwqdlnf ) View more
NCT02656303 (CTgov)	Phase 2	Chronic Lymphocytic Leukemia	116	Ublituximab+Umbralisib (Parent Study Arm B)	gplezbpylb(sssdgfwvcg) = ilucybwfnz eenwcmufab (lpoetivivq, bdbwbekytt - clgrsfhrgh) View more	-	22 Jun 2023
				Ublituximab+Umbralisib (Parent Study Arm C)	gplezbpylb(sssdgfwvcg) = pekwtucnda eenwcmufab (lpoetivivq, zwytxdvnlo - vpthduqfhm) View more