Delving into the Latest Updates on Exagamglogene Autotemcel with Synapse

RegulationPriority Review (US), Fast Track (US), Orphan Drug (US), Rare Pediatric Disease (US), Orphan Drug (EU), PRIME (EU), Regenerative Medicine Advanced Therapy (US), Conditional marketing approval (GB), Priority Review (CA)

Login to view First Approval Timeline

An International, Multicenter, Phase I Open Label Study to Evaluate Safety and Efficacy of Administration of Autologous CD34+ Cells Gene Edited Ex Vivo Using a CRISPR/AAV6 Platform to Introduce a Codon Optimized cDNA Version of the Red-Cell Type Pyruvate Kinase Genein Adult and Pediatric Patients with Severe Pyruvate Kinase

Start Date09 Nov 2023

Sponsor / Collaborator

Shanghai Children's Medical Center

NCT05477563 / RecruitingPhase 3

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.

Start Date02 Aug 2022

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

[+1]

100 Clinical Results associated with Exagamglogene Autotemcel

Login to view more data

100 Translational Medicine associated with Exagamglogene Autotemcel

Login to view more data

100 Patents (Medical) associated with Exagamglogene Autotemcel

Login to view more data

12

Literatures (Medical) associated with Exagamglogene Autotemcel

01 May 2023·Nature reviews. Drug discovery

First CRISPR therapy seeks landmark approval.

Author: Kingwell, Katie

Vertex and CRISPR Therapeutics′s first-in-modality genome-editor exa-cel, for the treatment of two haemoglobinopathies, has entered the regulatory spotlight.

01 May 2023·Human gene therapy

CRISPR Therapeutics, Vertex Complete Rolling Biologics License Applications for Exa-Cel in Sickle Cell Disease, Beta Thalassemia.

Article

Author: Philippidis, Alex

01 Mar 2023·Molecular therapy : the journal of the American Society of Gene Therapy

Genome editing coming of age for hemoglobinopathy

Author: Jiang, Haiyan

Following remarkable developments in the past 10 years, CRISPR-Cas9-based genome editing is coming of age and poised to offer a functional cure for severe beta-hemoglobinopathy, including transfusion-dependent thalassemia and sickle cell disease.SCD is among the most common monogenic hereditary conditions, affecting more than 6 million people worldwide, with ~300,000 new annual diagnoses.The only curative treatment was bone marrow hematopoietic stem cell transplant, which was limited by the shortage of HLA-matched healthy donors.Now, this issue can be addressed using autologous hematopoietic stem and progenitor cell (HSPC)-based genome editing therapies.The alternative approach is to mimic the naturally occurring mutations of the HBG 1/2 promoter, as in hereditary persistence of fetal Hb.Severe adverse events relating to exa-cel treatment were observed in two patients with beta-thalassemia.Nevertheless, as a new therapeutic modality, the long-term safety of a genome editing product is of paramount importance and a key product differentiation.With continued innovation and technol. advancement, authors may eventually reach a truly accessible and affordable product that employs in vivo delivery of a single-dose, curative treatment that circumvents the need for genotoxic chemotherapy conditioning.

288

News (Medical) associated with Exagamglogene Autotemcel

18 Jun 2024

·www.biospace.com

Enlaza Therapeutics Appoints Jeffrey Leiden, M.D., Ph.D., as a Key Advisor

Executive Chairperson and former CEO of Vertex Pharmaceuticals to help guide the development of a high-value pipeline of first-in-class covalent protein drugs from Enlaza’s War-Lock™ platform LA JOLLA, Calif.--(BUSINESS WIRE)-- Enlaza Therapeutics, the first covalent biologic platform company, today announced the appointment of Dr. Jeffrey Leiden, Executive Chairperson of Vertex Pharmaceuticals, as a key advisor to the company. Dr. Leiden has more than 40 years of experience in the biopharma industry developing life-improving medicines and building companies that transform the industry. “Jeff is one of the most accomplished and admired leaders in our industry. He has dedicated his career to developing important first-in-class medicines from novel breakthrough technologies that have helped millions of people with serious diseases,” said Sergio Duron, Ph.D., CEO of Enlaza Therapeutics. “With our War-Lock platform, we can create covalent protein drugs with the potential to improve treatments for many diseases. Jeff’s guidance will be invaluable as we establish a diverse pipeline and advance our lead assets toward clinical development.” "While covalency has been a long-standing strategy in small molecule drug development, Enlaza is the first to incorporate covalency into biologics, unlocking a new class of protein therapeutics," said Dr. Leiden. "I look forward to working closely with the Enlaza team to realize the full potential of this exciting new drug discovery and development platform and help create meaningful new medicines for patients.” As CEO and President of Vertex from 2012 through 2020, Dr. Leiden built a robust pipeline of drug candidates, with a particular focus on therapies that cure or modify the course of disease. Under his leadership, Vertex delivered the first and only medicines to treat the underlying cause of cystic fibrosis for patients with certain forms of the disease, including KALYDECO®, ORKAMBI®, SYMDEKO® and TRIKAFTA®. In 2015, he established a collaboration with CRISPR Therapeutics to develop transformative therapies for sickle cell disease (SCD), beta thalassemia (TDT) and other diseases; and in 2023, CASGEVY™ was approved as the first gene-editing therapy in the world for SCD and TDT. In 2019, he led the Vertex acquisition of Semma Therapeutics to develop a clinical program to investigate what may be the first potentially curative stem cell-based therapy for type 1 diabetes. Prior to joining Vertex, Dr. Leiden was a managing director at Clarus Ventures, a life sciences venture capital firm, from 2006 through 2012. Dr. Leiden was President, Chief Operating Officer and Chief Scientific Officer of Abbott Laboratories, Pharmaceuticals Products Group, and a member of the board of directors of Abbott Laboratories from 2000 to 2006. At Abbott he led the development and commercialization of HUMIRA®. From 1987 to 2000, Dr. Leiden held several academic appointments, including the Rawson Professor of Medicine and Pathology and Chief of Cardiology and Director of the Cardiovascular Research Institute at the University of Chicago, the Elkan R. Blout Professor of Biological Sciences at the Harvard School of Public Health, and Professor of Medicine at Harvard Medical School. He is an elected member of both the American Academy of Arts and Sciences and the National Academy of Medicine. About the War-Lock™ Platform Enlaza’s covalent biologic platform, called War-Lock, creates highly specific therapeutic warheads that covalently bind to drug targets of interest. This white-space technology enables, for the first time, a covalent-acting protein drug that retains the selectivity of small-format biologics. Protein drugs produced by the platform can be modified to incorporate various payloads and achieve specific delivery to target tissues with high fidelity. About Enlaza Therapeutics Enlaza Therapeutics is pioneering the field of covalent biologics. This novel class of protein therapeutics has the potential to delivers more efficacious and safer treatments for patients. The company's proprietary War-Lock™ platform leverages leading synthetic biology technology for site-specific covalent coupling driven by drug binding. Enlaza is building a pipeline of first-in-class covalent biologics. For more information, please visit .

Executive Change

16 Jun 2024

·firstwordpharma.com

EHA24: Vertex highlights longer-term benefits of Casgevy in blood disorders

Vertex Pharmaceuticals has unveiled longer-term data from clinical trials of its CRISPR-based gene-editing therapy Casgevy (exagamglogene autotemcel), confirming "consistent and durable" benefits of the treatment in patients with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT).The findings, presented at the European Hematology Association (EHA) annual meeting on Friday, are likely to help Vertex and partner CRISPR Therapeutics keep up the launch momentum for Casgevy, which was approved by the FDA in December for SCD – along with bluebird bio's rival gene therapy Lyfgenia (lovotibeglogene autotemcel) – and later also had TDT added to its label.The readouts were centred on the CLIMB-111 and -121 trials, as well as the CLIMB-131 long-term follow-up study. Overall, Vertex said the data were drawn from over 100 patients treated with Casgevy, with the longest follow-up now extending beyond five years.According to the company, efficacy data remain "consistent" with the previously reported primary and key secondary endpoints, and continue to show sustained and "stable levels" of foetal haemoglobin (HbF) and allelic editing over time.Vertex said that 36 of 39 SCD evaluable patients (92.3%) in CLIMB-121 study were free from vaso-occlusive crises (VOCs) for a minimum of 12 consecutive months. On average, patients remained VOC-free for 27.9 months, with the longest duration being 54.8 months. Further, 38 patients (97.4%) had no hospitalisations related to VOCs for at least 12 consecutive months.In the CLIMB-111 study, 49 out of 52 evaluable TDT patients (94.2%) achieved transfusion independence for at least 12 consecutive months, with a mean weighted haemoglobin of at least 9 g/dL. The average duration of transfusion independence was 31 months, with a maximum of 59.4 months. Moreover, all TDT patients with a minimum of 16 months of follow-up are now transfusion-free. Two of three patients who initially did not achieve transfusion independence later achieved this milestone in the long-term follow-up study, while the third has been transfusion free for 3.4 months.For both SCD and TDT cohorts, Vertex said that edited BCL11A alleles persisted over time in bone marrow and peripheral blood, "indicating successful editing in the long-term haematopoietic stem cells." All patients also achieved successful engraftment of neutrophils and platelets after their Casgevy infusion.

Drug ApprovalGene TherapyClinical ResultClinical Study

14 Jun 2024

·www.fiercepharma.com

Vertex presents longer-term data that shows durability and consistency of Casgevy

At the European Hematology Association (EHA) conference, Vertex presented long-term data showing the durability and effectiveness of Casgevy for patients who have taken the gene therapy for sickle cell disease or transfusion-dependent beta thalassemia. Six months after Vertex earned a historic FDA approval for sickle cell disease (SCD) gene therapy Casgevy (exa-cel), long-term data is beginning to show the consistent efficacy and durability of the treatment, which is the first ever to be developed using CRISPR gene editing technology. Of 39 SCD patients who have received Casgevy with at least 16 months of follow-up, 36 (92%) have been free of vaso-occlusive crises (VOCs), the debilitating pain episodes that accompany the disorder, for at least 12 consecutive months. The mean duration for patients to remain VOC-free was 28 months, with one patient reaching 55 months, Vertex said. Additionally, of those 39 patients, all but one were free of hospitalization related to VOCs for at least 12 consecutive months. The results are consistent with previously reported primary and secondary endpoints in the trial. In addition to presenting SCD data Friday at the European Hematology Association (EHA) conference in Madrid, Vertex also provided similar results for patients who have received Casgevy for transfusion-dependent beta thalassemia (TDT). Vertex and CRISPR Therapeutics scored FDA approval in the indication five months ago. Of 52 TDT patients with at least 16 months of follow-up, 49 (94%) achieved transfusion independence for at least 12 straight months. The mean duration of transfusion independence was 31 months, with one patient reaching 59 months. Additionally, all 52 patients in the study are now transfusion-free. Two of the three patients who did not initially achieve independence have now been transfusion-free for at least a year. The third patient has progressed into a fourth month of transfusion independence. In both groups, Vertex said that patients reported “sustained clinically meaningful improvements in their quality of life and functional well-being.” Also, in both groups, levels of the diagnostic biomarker BCL11A were stable over time in bone marrow and peripheral blood, indicating successful editing in the long-term hematopoietic stem cells, Vertex added. The data should help bolster Vertex’s push to gain marketing authorization for Casgevy in the U.K. A month ago, the U.K.’s drug pricing gatekeeper, the National Institute for Health and Care Excellence (NICE), did not recommend Casgevy for commercialization in its draft guidance. In the U.S., the one-time treatment costs $2.2 million. Europe signed off on Casgevy in February. “The comprehensive data set presented today for adult and adolescent TDT patients adds to the growing body of evidence for Casgevy and it is important to now ensure the availability of this innovative treatment to patients in the real world,” Franco Locatelli, M.D., Ph.D., professor of pediatrics at the Catholic University of the Sacred Heart of Rome, said in a release. “With the longest follow-up now more than five years, alongside stable editing and sustained fetal hemoglobin levels, I have conviction in the durable benefit to the patients treated with Casgevy.”

Clinical ResultDrug ApprovalGene Therapy

100 Deals associated with Exagamglogene Autotemcel

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15572

R&D Status

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Beta-Thalassemia	EU	Vertex Pharmaceuticals, Inc.	09 Feb 2024
Beta-Thalassemia	IS	Vertex Pharmaceuticals, Inc.	09 Feb 2024
Beta-Thalassemia	LI	Vertex Pharmaceuticals, Inc.	09 Feb 2024
Beta-Thalassemia	NO	Vertex Pharmaceuticals, Inc.	09 Feb 2024
Transfusion-dependent Thalassemia	US	Vertex Pharmaceuticals, Inc.	31 Jan 2024
Anemia, Sickle Cell	GB	CRISPR Therapeutics AG	16 Nov 2023
Anemia, Sickle Cell	GB	Vertex Pharmaceuticals, Inc.	16 Nov 2023
Transfusion-dependent Beta Thalassemia	GB	CRISPR Therapeutics AG	16 Nov 2023
Transfusion-dependent Beta Thalassemia	GB	Vertex Pharmaceuticals, Inc.	16 Nov 2023

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03745287 (CLIMB SCD-121, EHA2024) Manual	Phase 3	Anemia, Sickle Cell	24	exa-cel	ezmztlwati(yeeudzjyht) = By month 6, EQ-5D-5L health utility US index score and EQ VAS score showed substantial improvements,which were maintained through month 24 (change at month 24 [n=17]: 0.13 [0.19]; minimal clinically important difference [MCID] 0.078 and 26.9 [22.6]; MCID 7 to 10, respectively). inchyriiwo (ntizqgpvjw ) View more	Positive	14 May 2024
NCT03745287 (CLIMB SCD-121, EHA2024) Manual	Phase 3	Anemia, Sickle Cell	46	Exagamglogene autotemcel	ocsupujhnj(ifwmiysqxh) = kgphswnazb tlkbhrpiss (mbzcyfkmum, 79 - 99) View more	Positive	14 May 2024
NCT03655678 (CTX001-111 \| CLIMB THAL-111, EHA2024) Manual	Phase 3	Transfusion-dependent Thalassemia	24	Exagamglogene autotemcel	wdflgwoocw(xvfknsciar) = ftaikzwhas mefavivhpm (xhrfahresd, 0.21) View more	Positive	14 May 2024
NCT03655678 (CTX001-111, FDA) Manual	Phase 2/3	Transfusion-dependent Beta Thalassemia	52	CASGEVY	fggwafjojd(waylxyiyad) = umplkedceg souaqvsvwp (wfvayvsusr, 75.7 ~ 100) View more	Positive	07 Feb 2024
CLIMB THAL-111 (ASH2023)	Phase 3	Transfusion-dependent Beta Thalassemia	52	Exagamglogene autotemcel	vouoavnoel(utcdfoaumb) = ngejduglln lqugewevsv (gqdfsrbgom ) View more	Positive	11 Dec 2023
CLIMB SCD-121 (ASH2023)	Phase 3	Anemia, Sickle Cell	42	Exagamglogene autotemcel	ngwbkmtbnd(tcrocfckmh) = zjozvufhjj rquoitithr (zdpnkchbqz, 75.1% - 99.9%) View more	Positive	11 Dec 2023
CLIMB TDT-111 (ASH2023)	Phase 3	Transfusion-dependent Beta Thalassemia	35	Exagamglogene autotemcel	tscqjauedc(nthystyxgj) = arzqppvnav popjdniazi (xsqrdpyhfz ) View more	-	11 Dec 2023
NCT03745287 (FDA) Manual	Phase 2/3	Anemia, Sickle Cell	44	CASGEVY	llkusnwmjd(bqlqleybfr) = qgmrymwhhf gzflguaoja (qklmxurbwo, 77.9 - 100.0) View more	Positive	08 Dec 2023
Biospace Manual	Not Applicable	Anemia, Sickle Cell	29	Casgevy	shilvhyryr(cugjxbiqfj) = Common adverse events included fatigue, fever, nausea and a heightened risk of infections. gwaftawofb (tldfpxohks )	Positive	16 Nov 2023
Biospace Manual	Not Applicable	Transfusion-dependent Beta Thalassemia	42	Casgevy	ktjkptpfsh(uzseoszmaf) = Common adverse events included fatigue, fever, nausea and a heightened risk of infections. lcvcggmjhs (jrdwzehsna )	Positive	16 Nov 2023