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)

+ [11]

Target

CD20

Mechanism

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

+ [2]

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases+ [2]

Active Indication

Multiple sclerosis relapseChronic lymphocytic leukaemia refractorySmall Lymphocytic Lymphoma+ [1]

Inactive Indication

B-Cell LymphomaDiffuse Large B-Cell LymphomaFollicular Lymphoma+ [6]

Originator Organization

rEVO Biologics, Inc.LFB Biotechnologies SASU

Active Organization

AstraZeneca PLC

TG Therapeutics, Inc.

Neuraxpharm

+ [1]

Inactive Organization

Laboratoire Français du Fractionnement et des Biotechnologies

Drug Highest PhaseApproved

First Approval Date

US (28 Dec 2022),

Multiple sclerosis relapse

RegulationOrphan Drug (US)

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Gene Sequence

Sequence Code 4724843L

Source: *****

Sequence Code 15059H

Source: *****

The purpose of this study is to test if ublituximab changes walking functions and fall risk in people with relapsing multiple sclerosis (RMS). Twenty-five qualified people with RMS will undergo a 48-week ublituximab treatment. Before, 24 weeks into, and after the treatment, their ambulatory function, disability status, and cognition will be assessed. Additionally, they will experience large-scale slip perturbations on a treadmill under the protection of a safety harness at the last assessment. The outcome measures will be compared across the assessments to examine the effects of ublituximab on improving their walking function, disability status, cognition, and the responses to the unexpected slip perturbation.

Start Date01 Oct 2024

Sponsor / Collaborator

Georgia State University

[+1]

DRKS00034406 / RecruitingNot Applicable

Non-interventional, prospective, multicenter study to evaluate treatment satisfaction, treatment preference, quality of life, and tolerability under treatment with Briumvi® for relapsing forms of multiple sclerosis (RMS) with active disease in daily clinical practice - Briumvi® - Real World Experience Study (BRILL Study)

Start Date14 Jun 2024

Sponsor / Collaborator

Neuraxpharm Pharmaceuticals S.L.

CTIS2023-509555-13-00 / Recruiting

Pharmacokinetic/pharmacodynamic evaluation of ublituximab in patients with autoimmune diseases - TG1101-RMS-SC101

Start Date20 May 2024

Sponsor / Collaborator

TG Therapeutics, Inc.

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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75

Literatures (Medical) associated with Ublituximab

01 Nov 2024·Med

Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis

Article

Author: Fleischer, Vinzenz ; Steenken, Livia ; Protopapa, Maria ; Zipp, Frauke ; Bittner, Stefan ; Schraad, Muriel ; Steffen, Falk ; Pape, Katrin

BACKGROUNDAs B cell-depleting therapies in multiple sclerosis (MS) have gained significant importance in the last several years, their long-term safety profile is of considerable clinical interest. Late-onset neutropenia (LON) is a rare, but potentially severe, adverse event that was first described in patients with rheumatic disorders under therapy with rituximab. Ofatumumab was approved in 2021 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Neutropenia occurred in 0.2% of patients in clinical phase 3 trials, and to date, no cases of LON have been reported under ofatumumab treatment.METHODSHere, we report a case of repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment. Additionally, we review the literature on rare occurrences of LON in patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) undergoing B cell-depleting therapies, including rituximab, ocrelizumab, ofatumumab, inebilizumab, and ublituximab.FINDINGSIn our case, the patient presented with repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment leading to febrile infections, subsequent use of antibiotics, and application of granulocyte-colony-stimulating factor. After repetitive episodes of LON under both B cell-depleting strategies, cladribine was subsequently initiated. A nine-month follow-up showed a normal neutrophil count and no evidence of disease activity.CONCLUSIONSThis case highlights the significance of symptomatic late-onset blood count changes under both ocrelizumab and ofatumumab and emphasizes the importance of continuous monitoring of the differential blood count under B cell-depleting treatment.FUNDINGThis study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB CRC-TR-128 to F.Z., V.F., and S.B..; SFB 1080 and SFB CRC-1292 to F.Z..; and SFB/TRR 355 to S.B.) and the Hermann and Lilly Schilling Foundation (to S.B.).

01 Sep 2024·Critical Reviews in Oncology/Hematology

Safety profile of first-line targeted therapies in elderly and/or comorbid chronic lymphocytic leukaemia patients (unfit subpopulation). A systematic review and network meta-analysis

Review

Author: Stożek-Tutro, Anita ; Reczek, Monika ; Kawalec, Paweł

This systematic literature review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1-5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1-5. The use of Bruton's tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities.

01 Apr 2024·Journal of Neurology

Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment

Review

Author: Delgado, Silvia R ; Linker, Ralf A ; Rammohan, Kottil ; Faissner, Simon

AbstractThe recent success of anti-CD20 monoclonal antibody therapies in the treatment of multiple sclerosis (MS) has highlighted the role of B cells in the pathogenesis of MS. In people with MS, the inflammatory characteristics of B-cell activity are elevated, leading to increased pro-inflammatory cytokine release, diminished anti-inflammatory cytokine production and an accumulation of pathogenic B cells in the cerebrospinal fluid. Rituximab, ocrelizumab, ofatumumab, ublituximab and BCD-132 are anti-CD20 therapies that are either undergoing clinical development, or have been approved, for the treatment of MS. Despite CD20 being a common target for these therapies, differences have been reported in their mechanistic, pharmacological and clinical characteristics, which may have substantial clinical implications. This narrative review explores key characteristics of these therapies. By using clinical trial data and real-world evidence, we discuss their mechanisms of action, routes of administration, efficacy (in relation to B-cell kinetics), safety, tolerability and convenience of use. Clinicians, alongside patients and their families, should consider the aspects discussed in this review as part of shared decision-making discussions to improve outcomes and health-related quality of life for people living with MS.

138

News (Medical) associated with Ublituximab

07 Nov 2024

·endpts.com

Coherus restarts biosimilar supply after delays; Novavax ends Covid vaccine deal with UK

Welcome to Endpoints News’ manufacturing briefs, where we bring you essential news on new builds, collaborations, recalls and more. Coherus is resuming the supply of its Neulasta biosimilar after issues at a third-party labeling and packaging contractor caused delays in October. Production will resume this week. It has a backlog of around 120,000 units. Coherus first warned of supply delays in September. The biosimilar, branded as Udenyca, is approved to reduce infection in patients with low white blood cell count. Novavax has ended its Covid-19 vaccine supply agreement with the UK, the company said on Wednesday. The vaccine maker will return $10.3 million in quarterly installments over the next three years, totaling $123.8 million. Akebia Therapeutics disclosed in its third-quarter report that it has several ties with WuXi STA, a subsidiary of WuXi AppTec. The company has two contracts with WuXi and has the option to give 180 days notice to terminate them for any reason. One of the contracts ends in 2029 and the other in 2032. Charles River Laboratories reported a 1.6% drop in its total revenue for the third quarter of 2024 to $1.01 billion. But its manufacturing business increased 12% to $196.9 million because of heightened demand for its cell and gene therapy services, CEO James Foster said in an earnings call Wednesday. Charles River makes Vertex Therapeutics’ cell therapy Casgevy. The World Health Organization and its member states have allocated 899,000 doses of mpox vaccines to nine African countries. Around 85% of the doses will be supplied to the Democratic Republic of the Congo, which has the highest number of infections, according to a Wednesday release. CDMO AmplifyBio secured $50 million from investment capital provider Vitrian to bolster its manufacturing facility in New Albany, OH, according to a Tuesday release. Accord Healthcare received £50 million ($64.9 million) from the UK government to expand its facility in Fawdon, Newcastle upon Tyne, the company said Friday . It will build new manufacturing lines for an unnamed cancer drug and two autoimmune injectables. Around 50 new jobs will be added. Fujifilm Diosynth Biotechnologies has started the first phase of its factory expansion in Hillerød, Denmark, which will include adding six mammalian cell bioreactors, the company said Tuesday. The overall plan will be completed and operational by 2026. It will increase the facility to 51,500 square meters and add 2,200 new jobs. FujiFilm also said it signed a commercial manufacturing agreement with TG Therapeutics to make its therapy for relapsing forms of multiple sclerosis, according to a Monday announcement. Fujifilm will make Briumvi in Holly Springs, NC, which will be fully operational in 2025. Briumvi was FDA approved in December 2022. Evotec has sold an API manufacturing site in Halle, Germany, to Munich-based private equity firm Monacum Partners, the company said Tuesday. No financial details were disclosed. The CDMO Scorpius Holdings is partnering with Celltheon so it can offer cell line development and antibody discovery to its customers, according to a Monday announcement.

VaccineDrug ApprovalCell TherapymRNA

11 Oct 2024

·www.biospace.com

Sanofi, Denali Abandon Mid-Stage Multiple Sclerosis Study on Disappointing Data

iStock, JHVEPhoto Oditrasertib, which blocks the inflammatory RIPK1 protein, earlier this year also failed a Phase II trial in amyotrophic lateral sclerosis, forcing the company to discontinue its development a few months later. Sanofi is discontinuing a Phase II multiple sclerosis study of its investigational RIPK1 blocker oditrasertib after the candidate failed to meet its primary and key secondary endpoints, according to an SEC filing on Thursday by partner Denali Therapeutics. Denali and Sanofi were evaluating oditrasertib in the mid-stage K2 study , a randomized, double-blinded and placebo-controlled trial that enrolled more than 170 patients with relapsing-remitting multiple sclerosis (MS), secondary progressive MS or primary progressive MS. The primary efficacy endpoint was oditrasertib’s effect on serum neurofilament light chain levels. No specific details were provided in Denali’s SEC document, nor did the company identify which particular secondary outcomes oditrasertib missed. The California biotech also did not address oditrasertib’s safety profile. Designed to be orally available, oditrasertib is an investigational inhibitor of the RIPK1 protein, which is a crucial signaling player in inflammatory and cell death pathways. In neurodegenerative diseases, RIPK1—along with other proteins from the same family— tends to be overactivated , leading to widespread inflammation and large-scale cell death in the brain. By targeting RIPK1, oditrasertib disrupts this pathological process, in turn preserving the integrity and function of the brain. Despite a promising mechanism of action, however, oditrasertib has had a challenging clinical showing recently. In April 2024, Sanofi announced plans to terminate a Phase II trial of oditrasertib in amyotrophic lateral sclerosis (ALS) after a disappointing mid-stage readout. A few months earlier, in February 2024, Sanofi and Denali announced that oditrasertib failed the Phase II HIMALAYA study in ALS , unable to significantly improve disease severity, as measured by the ALS Functional Rating Scale-Revised. Developing effective therapies for MS has proven difficult. In September 2024, another Sanofi asset, the BTK inhibitor tolebrutinib, failed to significantly improve relapse rates in two Phase III studies. Tolebrutinib redeemed itself a few weeks later by significantly delaying disability onset in patients with non-relapsing secondary progressive MS in a third Phase III trial. That same month, a study published in the peer-reviewed journal Neurology raised questions about the use of anti-CD20 antibodies in multiple sclerosis. According to its findings, there appear to be no significant difference in relapse or the progression of disability between patients who were given these therapies versus those who were untreated. The study focused on primary progressive multiple sclerosis, for which the only approved anti-CD20 therapy is Roche’s Ocrevus (ocrelizumab). Other agents in the same drug class are also approved for relapsing forms of MS, including Novartis’ Kesimpta (ofatumumab) and TG Therapeutics’ Briumvi (ublituximab).

Phase 2Phase 3Drug ApprovalClinical Result

30 Sep 2024

·www.fiercehealthcare.com

HHS releases cost savings for 54 prescriptions including cancer drug

The Medicare rebate program, under the Inflation Reduction Act, keeps chugging along. The Biden administration is once again trumpeting the Medicare Prescription Drug Inflation Rebate Program to prove to voters it is lowering drug prices.Through the program, 54 drugs will be less expensive for Medicare enrollees because of a lower Part B coinsurance rate from Oct. 1 through the end of the year. This is because drug companies raised the price of these 54 drugs faster than the rate of inflation, affecting 822,000 beneficiaries.“The President’s lower cost prescription drug law continues to put money back in the pockets of seniors and people with disabilities,” said Department of Health and Human Services (HHS) Secretary Xavier Becerra in a statement. “President Biden and Vice President Harris promised to lower prescription drug costs—and they have delivered.”The program has been in effect since April 2023. Each quarter, a new selection of drugs is discounted through the Inflation Reduction Act. This time, the program could could save patients $3,000 on the drug Kymriah, which treats cancer, the administration said. Other drugs included in this round are Briumvi for multiple sclerosis, Krystexxa for chronic gout and Tivdak used to treat cervical cancer.It is expected enrollees could save as much $3,854 depending on the prescription drug they need.HHS discounted drugs for bladder cancer, osteoporosis, infections and more this year. Starting next year, Medicare Part D enrollees will have a $2,000 cap on annual out-of-pocket prescription drug costs. In August, the feds announced savings on 10 prescription drugs through the drug negotiation program, which drastically reduces the price of drugs like Enbrel, Jardiance and Januvia, starting in 2026. A new list for negotiation in 2027 will be announced in February.The Centers for Medicare & Medicaid Services will start invoicing prescription drug companies for rebates owed to Medicare by fall 2025. These rebates are deposited to the Federal Supplementary Medical Insurance Trust Fund.

100 Deals associated with Ublituximab

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External Link

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
Follicular Lymphoma	Preclinical	GB	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Preclinical	GB	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Preclinical	AU	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Preclinical	AU	TG Therapeutics, Inc.	25 May 2016
Mantle-Cell Lymphoma	Preclinical	US	TG Therapeutics, Inc.	19 Mar 2015
Mantle-Cell Lymphoma	Preclinical	US	TG Therapeutics, Inc.	19 Mar 2015
Chronic Lymphocytic Leukemia	Preclinical	IL	TG Therapeutics, Inc.	27 Jan 2015
Chronic Lymphocytic Leukemia	Preclinical	US	TG Therapeutics, Inc.	27 Jan 2015
Chronic Lymphocytic Leukemia	Preclinical	IL	TG Therapeutics, Inc.	27 Jan 2015
Chronic Lymphocytic Leukemia	Preclinical	US	TG Therapeutics, Inc.	27 Jan 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ULTIMATE (Corporate Publications) Manual	Phase 3	Multiple sclerosis relapse	81	ublituximab	(ckcchslvis) = Statistically significant average treatment effects, holding baseline value, sex, and age constant, were observed for the overall DA Score and each of the 4 Disease Pathway Scores, resulting in lower scores for the ublituximab arm compared to the teriflunomide arm (p<0.05; Bonferroni corrected). xrbefhmwou (piekqjefsp ) View more	Positive	18 Sep 2024
				teriflunomide
NCT03277248 \| NCT03277261 (ULTIMATE, Corporate Publications) Manual	Phase 1/2	Multiple sclerosis relapse	1,094	teriflunomide+Ublituximab	(retingxkfn) = whxwqzumre uxkzkisfrz (rltjygbyrd ) View more	Positive	18 Sep 2024
				Ublituximab	(retingxkfn) = ikokwjpbjr uxkzkisfrz (rltjygbyrd ) View more
ENHANCE (Corporate Publications) Manual	Phase 3	Multiple sclerosis relapse	126	Ublituximab Day 1 Dose: 150 mg (Non-Depleted)	xxjiakgxch(duitstrrlo) = gemphdomyx qfpimbxlgc (bzplqearau ) View more	Positive	18 Sep 2024
				Ublituximab Day 1 Dose: 450 mg (Depleted)	xxjiakgxch(duitstrrlo) = rdsmqfjaeu qfpimbxlgc (bzplqearau ) View more
NCT02612311 (UNITY-CLL, CTgov)	Phase 3	Chronic Lymphocytic Leukemia	603	Ublituximab+Umbralisib (Experimental: Arm A: Ublituximab + Umbralisib)	qowtdmoybw(eyuqoulpnn) = hzxemappeh xsoldsegai (jeexjafasg, qxxlmoftsf - lsjvpwjtim) View more	-	07 May 2024
				Obinutuzumab+Chlorambucil (Active Comparator: Arm B: Obinutuzumab + Chlorambucil)	qowtdmoybw(eyuqoulpnn) = rcjvfcxbbe xsoldsegai (jeexjafasg, tppebxelbj - oghpklfywq) 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))	djtgnnqoab(pvrotjnqcw) = ptbrmqfdzi wprwwcyyav (pyoaatagbv, xboslhgxgk - xgeujgfegw) View more	-	19 Apr 2024
				Ublituximab+Venetoclax+Umbralisib (Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V))	bhthjdarll(sumfviratx) = xfgykzgbpo jhxhljhbar (ievzzaiwny, rfnvbtiqph - wmocofbcjq) View more
NCT05877963 (ENHANCE, ACTRIMS2024) Manual	Phase 3	Multiple sclerosis relapse	-	Ublituximab 450 mg infusion, 2 hr	(vzsthhopyn) = xfwvesmlbq nbiqhmlznr (tubxhtjlul )	Positive	29 Feb 2024
				Ublituximab 450 mg infusion, 1 hr	(vzsthhopyn) = qgvdeforye nbiqhmlznr (tubxhtjlul )
NCT04624633 (ASH2023)	Phase 2	Chronic Lymphocytic Leukemia	29	Acalabrutinib	(ivvegryghw) = wrrlhhzhcr uxuilglqyk (vgaexqnhzi ) View more	-	09 Dec 2023
				Umbralisib	(ivvegryghw) = dsdatukaiv uxuilglqyk (vgaexqnhzi ) View more
NCT04508647 (CTgov)	Phase 2	Follicular Lymphoma \| Marginal Zone B-Cell Lymphoma	4	Ublituximab (Ublituximab Only)	ntfsndlsvc(logbbsgpkp) = jghyfmheiv lytrsgfirh (uogbusqjsr, npdlraikmt - kvsmxokcko) View more	-	09 Nov 2023
				Ublituximab+Umbralisib (Ublituximab First, Then Ublituximab and Umbralisib)	wtrfjcxchp(exprpfkfmu) = gvpaqkxvhs snxczcljpc (nnyupyorbm, ajeqczhtdj - rjzzvdpxxz) View more
ULTIMATE I & II (ECTRIMS2023)	Phase 3	CD20	-	Ublituximab 450 mg	wpfewweztz(lsjclumheb) = pjarlomhph cqiaslyyjd (dauhpkmwky, -0.82 to 13.46) View more	Positive	30 Sep 2023
				Teriflunomide 14 mg	wpfewweztz(lsjclumheb) = fkskkcrylk cqiaslyyjd (dauhpkmwky, 17.77 - 31.96) View more
NCT04692155 (CHOP U2, CTgov)	Phase 1/2	Mantle-Cell Lymphoma	1	Ublituximab+Umbralisib	wthcjmzbjn(ssuxdswbpa) = sgcjmzjuue ljcxbbudww (eevhwhvvve, tylxvywhdw - symtlquuez) View more	-	28 Sep 2023