On June 15, 2024 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, reported detailed results from the global Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent (NTD) alpha- or beta-thalassemia in a plenary session (abstract #S104) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 (EHA2024) Hybrid Congress, which is being held June 13-16, 2024, in Madrid, Spain (Press release, Agios Pharmaceuticals, JUN 15, 2024, View Source [SID1234644352]). In a related poster presentation (abstract #P1529), the company presented additional data from the ENERGIZE study highlighting clinically meaningful improvements in health-related quality of life measures and patient-reported outcomes among patients in the mitapivat arm compared to those in the placebo arm.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The ENERGIZE study achieved its primary endpoint, with mitapivat demonstrating a statistically significant increase in hemoglobin response rate compared to placebo. Statistical significance was also achieved for both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and hemoglobin concentration. These improvements were observed across all pre-specified subgroups.

"The data from the ENERGIZE study are compelling, with mitapivat-treated patients achieving meaningful improvements in non-transfusion-dependent thalassemia’s hallmark symptom of anemia as well as in key measures of how patients feel and function," said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. "Together with the recently announced positive results from the ENERGIZE-T study of mitapivat in adults with transfusion-dependent thalassemia, the detailed ENERGIZE results underscore mitapivat’s potential to become an important treatment option for all subtypes of thalassemia – alpha- and beta-thalassemia, transfusion-dependent and non-transfusion-dependent – with the convenience of a pill. We look forward to working with regulators as we anticipate filing for approval in the U.S. by the end of this year."

"I am pleased to present the results of the ENERGIZE study to my esteemed colleagues and believe they will share my enthusiasm for the positive impact mitapivat may have for patients with non-transfusion-dependent alpha- or beta-thalassemia," said Ali Taher, M.D., Ph.D., Professor of Medicine, Hematology & Oncology and Director – Naef K. Basile Cancer Institute, American University of Beirut Medical Center in Beirut, Lebanon; an investigator in the ENERGIZE study. "Globally, there are currently no approved oral treatments for non-transfusion-dependent thalassemia, which is characterized by anemia, ineffective erythropoiesis, hemolysis and iron overload and can cause severe complications, reduced quality of life and shortened lifespan. Based on the data collected in the ENERGIZE study, mitapivat has the potential to become a foundational treatment for non-transfusion-dependent thalassemia."

"The ENERGIZE data presented at this congress show that non-transfusion-dependent alpha- or beta-thalassemia patients treated with mitapivat experienced clinically meaningful improvements in fatigue and walking capacity, as well as improvements in patient-reported outcomes across a range of disease symptoms," said Kevin Kuo, M.D., MSc, FRCPC; Division of Hematology, University of Toronto in Ontario, Canada; an investigator in the ENERGIZE study. "There is a tremendous need for oral therapies that can improve how people with thalassemia feel and function and reduce the impact of the disease on their lives. Patients with alpha- or beta-thalassemia, regardless of transfusion status, frequently report negative effects on daily activities and physical functioning. On a number of domains of health-related quality of life, adults with non-transfusion-dependent thalassemia experience even greater symptom burden than their transfusion-dependent counterparts. I am excited about the potential of mitapivat to support quality of life improvements for these individuals."

Agios also recently announced positive results from the Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia. The company intends to file for regulatory approval of mitapivat as a treatment for thalassemia by the end of 2024, incorporating all available data from both studies.

Results for the Phase 3 ENERGIZE study were as follows:

A total of 194 patients were enrolled in the study, with 130 randomized to mitapivat 100 mg twice-daily (BID) and 64 randomized to matched placebo. 122 (93.8%) in the mitapivat arm and 62 (96.9%) in the placebo arm completed the 24-week double-blind period of the study.
Baseline demographics and characteristics were balanced between mitapivat and placebo arms, and representative of a population of non-transfusion dependent thalassemia patients.
The study met the primary endpoint of hemoglobin response. Hemoglobin response was defined as an increase of ≥1 g/dL in average hemoglobin concentrations from week 12 through week 24 compared with baseline.
42.3% (n=55/130) of patients in the mitapivat arm achieved a hemoglobin response, compared to 1.6% (n=1/64) of patients in the placebo arm (2-sided p<0.0001).
Among patients who achieved hemoglobin response in the mitapivat arm, the mean change from baseline in average hemoglobin concentration from week 12 to 24 was 1.56 g/dL.
Hemoglobin response rates were higher among those treated with mitapivat compared to placebo across all prespecified subgroups, including:
Thalassemia genotype: 23.8% (n=10/42) of alpha-thalassemia patients in the mitapivat arm achieved a hemoglobin response, compared to no alpha-thalassemia patients in the placebo arm. 51.1% (n=45/88) of beta-thalassemia patients in the mitapivat arm achieved a hemoglobin response, compared to 2.3% (n=1/44) of beta-thalassemia patients in the placebo arm.
Baseline hemoglobin concentration: 47.4% (n=45/95) of patients whose baseline hemoglobin concentration was ≤9.0 g/dL in the mitapivat arm achieved a hemoglobin response, compared to 2.1% (n=1/47) of patients in the placebo arm. 28.6% (n=10/35) of patients whose baseline hemoglobin concentration was between 9.1 and 10.0 g/dL achieved a hemoglobin response, compared to no patients in the placebo arm.
Treatment with mitapivat also demonstrated statistically significant improvements compared to placebo for both key secondary endpoints:
The average change from baseline (95% confidence interval) in FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) subscale score from week 12 to week 24 was 4.85 (3.41, 6.30) in the mitapivat arm compared to 1.46 (–0.43, 3.34) in the placebo arm (p=0.0026).
The average change from baseline (95% confidence interval) in average hemoglobin concentration from week 12 to week 24 was 0.86 (0.73, 0.99) g/dL in the mitapivat arm compared to –0.11 (–0.28, 0.07) g/dL in the placebo arm (p<0.0001).
Improvements were observed in patients treated with mitapivat across measures of health-related quality-of-life, including the six-minute walk test and the Patient Global Impression of Change (PGIC) fatigue, walking capacity, and thalassemia symptoms subscales.
Six-minute walk test: The average change (95% confidence interval) from baseline to week 24 was 30.48 (19.31, 41.64) meters in the mitapivat arm compared to 7.11 (–7.39, 21.62) in the placebo arm.
PGIC: A higher proportion of patients in the mitapivat arm reported improvements in fatigue as per PGIC versus those in the placebo arm at weeks 12, 16, 20, and 24. A higher proportion of patients in the mitapivat arm reported improvements in thalassemia symptoms and walking capacity as per PGIC at week 24 versus those in the placebo arm.
Overall, during the 24-week double-blind period, incidence of adverse events was similar across mitapivat and placebo arms, with 82.9% (n=107) of patients in the mitapivat arm and 79.4% (n=50) of patients in the placebo arm experiencing treatment-emergent adverse events (TEAEs).
The most frequently reported TEAEs were headache, initial insomnia, nausea and upper respiratory tract infection.
3.9% (n=5) of patients in the mitapivat arm experienced Grade ≥3 treatment-related TEAEs. There were no serious TEAEs.
3.1% (n=4) of patients in the mitapivat arm experienced TEAEs leading to discontinuation; there were no TEAEs leading to discontinuation in the placebo arm.
Conference Call Information
Agios will host a virtual investor breakout session tomorrow, June 16, 2024, at 10:00 a.m. ET (4 p.m. CEST) to review the key clinical oral and poster presentations from the EHA (Free EHA Whitepaper)2024 meeting. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

About PYRUKYND (mitapivat)
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.

IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.

Drug Interactions:

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information and Summary of Product Characteristics for PYRUKYND.

On June 14, 2024 Galapagos NV (Euronext & NASDAQ: GLPG) reported that it will present encouraging new data from the ongoing Phase 1/2 ATALANTA-1 study of CD19 CAR-T candidate, GLPG5101, in relapsed/refractory non-Hodgkin lymphoma (R/R NHL) at the annual European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress (Press release, Galapagos, JUN 14, 2024, View Source [SID1234644384]). Galapagos’ product candidate GLPG5101 is produced using the company’s innovative, decentralized T-cell manufacturing platform.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The oral presentation includes updated safety and efficacy data for GLPG5101 in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). The presentation also includes durability and cellular kinetics data. At the data cut-off date of December 20, 2023, no unexpected safety findings were observed and treatment with GLPG5101 resulted in high complete response rates in all indications in this heavily pretreated patient population.

GLPG5101 was administered as a fresh product in 94% of patients with a median vein-to-vein time of seven days, eliminating the need for bridging therapy. T-cell subsets were assessed in the apheresis starting material and final CAR-T product. There was a higher proportion of early phenotypes of CD4+ and CD8+ CAR T cells (naive/stem cell memory and central memory T cells) in the final product compared with starting material, indicating an increase of those populations during the manufacturing process. This demonstrates the feasibility of Galapagos’ decentralized manufacturing platform to deliver a high-quality CAR T-cell product to patients.

The new data will be presented by Marie José Kersten, M.D., Professor of Hematology and Head of the Department of Hematology at the Amsterdam University Medical Center.

"We are committed to accelerating breakthrough innovations to extend the reach of CAR-T therapies to patients with rapidly progressing cancers," said Dr. Jeevan Shetty, M.D., Head of Clinical Development Oncology at Galapagos. "We are delighted to present promising new data for GLPG5101 at the EHA (Free EHA Whitepaper) congress. The high complete response rates, combined with low-grade CRS and ICANS, demonstrates the potential of GLPG5101 in addressing the critical needs of this patient population. The data also confirm the feasibility of our innovative decentralized T-cell manufacturing platform in delivering fresh, fit cells with a median vein-to-vein time of just seven days."

Key new data from the ongoing Phase 1/2 ATALANTA-1 study include:
As of the data cut-off date of December 20, 2023, 34 patients (17 in Phase 1 and 17 in Phase 2) received GLPG5101 with a median vein-to-vein time of seven days. Overall, safety results were available for 33 patients and efficacy results were available for 31 patients. The data are summarized below:

GLPG5101 showed an encouraging safety profile with most TEAEs1 of Grade 1 or 2; the majority of Grade ≥ 3 events were hematological. Two cases of CRS2 Grade 3 were observed in Phase 1 and one case of ICANS3 Grade 3 was observed in Phase 2.
In Phase 1, 14 of 16 efficacy-evaluable patients responded to treatment (objective response rate, ORR 87.5%), with 12 patients achieving a complete response (CR) (CR rate, CRR 75%). In Phase 2, 14 of 15 efficacy-evaluable patients responded to treatment (ORR 93.3%), and all responders achieved a complete response (CRR 93.3%).
High ORR and CRR were observed in the pooled Phase 1 and Phase 2 efficacy analysis set, split by indication:
In patients with DLBCL, 7 of 9 efficacy-evaluable patients responded to treatment (ORR 78%), with 5 patients achieving a complete response (CRR 56%).
In patients with FL or MZL, objective and complete responses were observed in 16 of 17 efficacy-evaluable patients (ORR and CRR 94%).
In patients with MCL, all 5 of 5 efficacy-evaluable patients responded to treatment (ORR and CRR 100%).
Durable responses were observed in the majority of responding patients:
71% of patients in Phase 1 had an ongoing response at data cut-off with median follow-up of 13.1 months.
100% of patients in Phase 2 had an ongoing response at data cut-off with median follow-up of 4.2 months.
Strong and consistent in vivo CAR-T expansion levels and products consisting of early phenotype T cells were observed in all doses tested.
Presentation details:

Abstract number/title Authors/Presenter Presentation date/time
Abstract #S243
Seven-Day Vein-to-Vein Point-of-Care Manufactured CD19 CAR T Cells (GLPG5101) in Relapsed/Refractory Non-Hodgkin Lymphoma: Results from the Phase 1/2 Atalanta-1 Trial Marie José Kersten, Kirsten Saevels, Sophie Servais, Evelyne Willems, Marte C. Liefaard, Stavros Milatos, Margot J. Pont, Claire Vennin, Eva Santermans, Anna D.D. Van Muyden, Maria T. Kuipers, Sébastien Anguille, Joost S.P. Vermaat Saturday, June, 15
12:15- 12:30 pm CET

​Session s422: Aggressive lymphoma – CAR-T cell therapy
Hall Dali 2

About the ATALANTA-1 study (EudraCT 2021-003272-13)
ATALANTA-1 is an ongoing Phase 1/2, open-label, multicenter study to evaluate the safety, efficacy and feasibility of decentralized manufactured GLPG5101, a CD19 CAR-T product candidate, in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). GLPG5101 is a second generation anti-CD19/4-1BB CAR-T product candidate, administered as a single fixed intravenous dose. The primary objective of the Phase 1 part of the study is to evaluate the safety and preliminary efficacy to determine the recommended dose for the Phase 2 part of the study. Secondary objectives include assessment of efficacy and feasibility of near the point-of-care manufacturing of GLPG5101. The dose levels that were evaluated in Phase 1 are 50×106 (DL1), 110×106 (DL2) and 250×106 (DL3) CAR+ viable T cells. The primary objective of the Phase 2 part of the study is to evaluate the objective response rate (ORR), while the secondary objectives include complete response rate (CRR), duration of response, progression free survival, overall survival, safety, pharmacokinetic profile, and the feasibility of decentralized manufacturing. Each enrolled patient will be followed for 24 months.

About non-Hodgkin lymphoma
Non-Hodgkin lymphoma is a cancer originating from lymphocytes, a type of white blood cell which is part of the body’s immune system. Non-Hodgkin lymphoma can occur at any age although it is more common in adults over 50 years old. Initial symptoms usually are enlarged lymph nodes, fever, and weight loss. There are many different types of non-Hodgkin lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow growing) types, and they can be formed from either B lymphocytes (B cells) or in lesser extent from T lymphocytes (T cells) or Natural Killer cells (NK cells). B-cell lymphoma makes up about 85% of non-Hodgkin lymphomas diagnosed in the US. Prognosis and treatment of non-Hodgkin lymphoma depend on the stage and type of disease.

About Galapagos’ T-cell manufacturing platform
Galapagos’ decentralized, innovative T-cell manufacturing platform has the potential for the administration of fresh, fit cells within a median vein-to-vein time of seven days, greater physician control and improved patient experience. The platform consists of an end-to-end xCellit workflow management and monitoring software system, a decentralized, functionally closed, automated manufacturing platform for cell therapies (using Lonza’s Cocoon) and a proprietary quality control testing and release strategy.

On June 14, 2024 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage biopharmaceutical company advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, reported the company will present additional positive interim Phase 1b expansion cohort data for IO-202 in patients with chronic myelomonocytic leukemia (CMML) at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting held virtually and in Madrid, Spain, June 13 – 16 (Press release, Immune-Onc Therapeutics, JUN 14, 2024, View Source [SID1234644351]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CMML is a rare hematologic malignancy with poor survival outcomes, incurable with conventional therapy, and has no effective standard of care. Currently, hypomethylating agents (HMA), including azacitidine (AZA), are the only FDA-approved treatment option for CMML with only a 7-17% complete remission (CR) rate.

Promising early-cycle responses, including a 53.8% (7 out of 13) CR rate (4 CR, 1 CR equivalent, and 2 CR bilineage), based on International Working Group 2023 response criteria, were observed in CMML patients treated with IO-202 in combination with AZA, with CRs lasting ten months and ongoing. The Phase 1b interim data continue to demonstrate that IO-202 is well tolerated.

"Chronic myelomonocytic leukemia remains a disease with poor prognosis and risk of progression into acute myeloid leukemia (AML), resulting in a critical need for innovative medicines," said IO-202 Phase 1b investigator Courtney DiNardo, M.D., MSCE, professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX. "We are encouraged by Phase 1b trial data showing early and sustained complete remissions among CMML patients, regardless of their prognosis or mutation status. This supports the potential of IO-202 in combination with azacitidine as a frontline therapy for CMML patients, and we are pleased to share these data with the medical community at EHA (Free EHA Whitepaper) this year."

"IO-202 has favorable tolerability, a well-understood mechanism of action, and a consistent efficacy response that supports further study as a treatment option in both AML and CMML patients," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "We look forward to continued collaborations with our investigators and the FDA to plan and conduct our registrational study in frontline CMML patients."

Poster presentation details:

Abstract Number: P792 (here)
Title: Targeting LILRB4 (ILT3) Using IO-202 in Patients with Chronic Myelomonocytic Leukemia (CMML): Interim Efficacy, Safety, and Mechanism of Action Data from the Phase 1b Expansion Cohort
Presenter: Ahmed Aribi, M.D., assistant professor, Division of Leukemia, City of Hope in Duarte, CA
Session Title: Myelodysplastic Syndromes – Clinical
Session Date and Time: Friday, June 14, 6-7 p.m. CEST

ABOUT CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)

CMML is a rare form of blood cancer, occurring in 4 of every 1,000,000 people in the United States each year,1 or about 1,100 annual cases.2 CMML is characterized by a high monocyte count (>1×109/L peripheral monocytes with monocytes ≥ 10% of white blood count) and dysplastic features in the bone marrow.1 Current FDA-approved therapies for CMML are all hypomethylating agents, including azacitidine, only achieving a 7%-17% complete response rate.1

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on monocytes and monocyte-derived cells. LILRB4 is expressed on certain hematologic cancer cells, such as myelomonocytic leukemia blasts, and on certain pathogenic cells involved in autoimmunity and inflammatory processes.

ABOUT IO-202

IO-202 is a first-in-class IgG1 antibody with specific, high-affinity binding to LILRB4 and depletes LILRB4 positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. As such, IO-202 is a targeted therapy with broad potential in blood cancers and autoimmune and inflammatory diseases.

IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the U.S., and the data was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in 2023. This Phase 1 trial has advanced to the dose expansion stage to evaluate IO-202 in combination with azacitidine (NCT04372433) in patients with newly diagnosed chronic myelomonocytic leukemia (CMML) who have not received any hypomethylating agents (HMA).

The U.S. Food and Drug Administration granted IO-202 Fast Track Designations for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory CMML, respectively. The FDA has also granted IO-202 Orphan Drug Designations for the treatment of AML and CMML, respectively.

On June 14, 2024 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported longer-term data for CASGEVY (exagamglogene autotemcel [exa-cel]) from global clinical trials in people with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT) (Press release, Vertex Pharmaceuticals, JUN 14, 2024, View Source [SID1234644350]). The results, presented at the annual European Hematology Association (EHA) (Free EHA Whitepaper) Congress, confirm the transformative, consistent and durable clinical benefits of CASGEVY over time. CASGEVY is the first and only approved CRISPR-based gene-editing therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data being presented are from more than 100 patients (46 SCD; 56 TDT) treated with exa-cel in clinical trials, with the longest follow-up now extending more than 5 years. The efficacy results are consistent with the previously reported primary and key secondary endpoints analyses from these exa-cel studies and continue to demonstrate transformative clinical benefit with durable and stable levels of fetal hemoglobin (HbF) and allelic editing.

"The transformative benefit seen in patients with sickle cell disease in the trial is impressive given the significant and cumulative burden of disease faced by people living with this blood disorder," said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital. "I am eager to offer this therapy and the opportunity of a potential functional cure to my eligible patients."

"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 as soon as possible," said Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Catholic University of the Sacred Heart of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Gesù Children’s Hospital. "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."

New data presented from CASGEVY pivotal trials

In SCD 36/39 (92.3%) evaluable patients (those with at least 16 months of follow-up) were free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12), consistent with the previously reported primary endpoint data. Mean duration of VOC-free was 27.9 months, with a maximum of 54.8 months.
38/39 (97.4%) patients with at least 16 months of follow-up were free from hospitalizations related to VOCs for at least 12 consecutive months (HF12), consistent with the previously reported key secondary endpoint data.
In TDT 49/52 (94.2%) evaluable patients (those with at least 16 months of follow-up) were transfusion-independent for at least 12 consecutive months with a mean weighted hemoglobin of at least 9 g/dL (TI12), consistent with the previously reported primary endpoint data. Mean duration of transfusion independence was 31.0 months, with a maximum of 59.4 months.
All TDT patients dosed with at least 16 months of follow up are transfusion free.
Two of the three patients who did not achieve TI12 in CLIMB-111 achieved TI12 in the long-term follow-up study, CLIMB-131, and have been transfusion independent for over one year. The third has been transfusion free for 3.4 months.
Both SCD and TDT patients reported sustained and clinically meaningful improvements in their quality of life, including physical, emotional, social/family and functional well-being, and overall health status.
In both SCD and TDT patients, edited levels of BCL11A alleles were stable over time in bone marrow and peripheral blood indicating successful editing in the long-term hematopoietic stem cells. All patients engrafted neutrophils and platelets after exa-cel infusion. The safety profile of exa-cel was generally consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.

These longer-term data for CASGEVY from the CLIMB clinical trials will be shared as outlined below:

Abstracts S273 and S274 will be oral presentations entitled "Exagamglogene Autotemcel For Severe Sickle Cell Disease," and "Exagamglogene Autotemcel For Transfusion-Dependent Beta-Thalassemia," on Sunday, June 16 at 12:15 CEST and 12:30 CEST, respectively.
Abstracts P1493 and P1525 will be poster presentations entitled "Health-Related Quality Of Life Improvements After Exagamglogene Autotemcel In Patients With Severe Sickle Cell Disease," and "Health-Related Quality Of Life Improvements After Exagamglogene Autotemcel In Patients With Transfusion-Dependent Βeta-Thalassemia," on Friday, June 14 at 18:00 CEST.
These presentations will include updated pivotal trial data from patients treated with CASGEVY in CLIMB-111 and CLIMB-121 and followed in CLIMB-131.
Vertex will also share five health economics abstracts at the EHA (Free EHA Whitepaper) Congress.

Abstract P1483 is entitled "Adherence, Treatment Use, and Clinical Outcomes in Patients With Sickle Cell Disease With Recurrent Vaso-Occlusive Crises Treated With L-Glutamine, Voxelotor, or Crizanlizumab in the United States."
Abstract P1506 is entitled "Mortality and Clinical Complications Among Patients with Sickle Cell Disease With Recurrent VOCs in Canada."
Abstract P1507 is entitled "Treatment Utilization and Clinical Complications in Patients with Sickle Cell Disease Receiving Frequent Red Blood Cell Transfusions in the United States."
Abstract P2191 is entitled "Clinical Complications and Treatment Use Among Patients With Sickle Cell Disease With Recurrent Vaso-Occlusive Crises in the Netherlands."
Abstract PB3248 is entitled "Clinical Complications Among Patients With Transfusion-Dependent Beta-Thalassemia in the Netherlands."
About Sickle Cell Disease (SCD)

SCD is a debilitating, progressive, life shortening genetic disease. SCD patients report health-related quality of life scores well below the general population and significant health care resource utilization. SCD affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or "sickled" red blood cells. The clinical hallmark of SCD is vaso-occlusive crises (VOCs), which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In Europe, the mean age of death for patients living with SCD is around 40 years. Stem cell transplant from a matched donor is a potentially curative option but is only available to a small fraction of people living with SCD because of the lack of available donors.

About Transfusion-Dependent Beta Thalassemia (TDT)

TDT is a serious, life-threatening genetic disease. TDT patients report health-related quality of life scores below the general population and significant health care resource utilization. TDT requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In Europe, the mean age of death for patients living with TDT is 50-55 years. Stem cell transplant from a matched donor is a potentially curative option but is only available to a small fraction of people living with TDT because of the lack of available donors.

About CASGEVY (exagamglogene autotemcel [exa-cel])

CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth.

CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

About the CLIMB Studies

The ongoing Phase 1/2/3 open-label trials, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after CASGEVY infusion. Each patient will be asked to participate in the ongoing long-term, open-label trial, CLIMB-131. CLIMB-131 is designed to evaluate the safety and efficacy of CASGEVY in patients who received CASGEVY in other CLIMB studies. The trial is designed to follow patients for up to 15 years after CASGEVY infusion.

U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY (exagamglogene autotemcel)

WHAT IS CASGEVY?

CASGEVY is a one-time therapy used to treat people aged 12 years and older with:

sickle cell disease (SCD) who have frequent vaso-occlusive crises or VOCs
beta thalassemia (β-thalassemia) who need regular blood transfusions
CASGEVY is made specifically for each patient, using the patient’s own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with sickle cell disease and eliminate the need for regular blood transfusions in people with beta thalassemia.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CASGEVY?

After treatment with CASGEVY, you will have fewer blood cells for a while until CASGEVY takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelet cells:
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of white blood cells:
fever
chills
infections
You may experience side effects associated with other medicines administered as part of the treatment regimen for CASGEVY. Talk to your physician regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

How will I receive CASGEVY?

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment with CASGEVY. It’s important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

STEP 1: Before CASGEVY treatment, a doctor will give you mobilization medicine(s). This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If CASGEVY cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from CASGEVY.

STEP 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make CASGEVY. It may take up to 6 months from the time your cells are collected to manufacture and test CASGEVY before it is sent back to your healthcare provider.

STEP 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in CASGEVY. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the infusion with CASGEVY.

STEP 4: One or more vials of CASGEVY will be given into a vein (intravenous infusion) over a short period of time.

After the CASGEVY infusion, you will stay in hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

What should I avoid after receiving CASGEVY?

Do not donate blood, organs, tissues, or cells at any time in the future
What are the possible or reasonably likely side effects of CASGEVY?

The most common side effects of CASGEVY include:

Low levels of platelet cells, which may reduce the ability of blood to clot and may cause bleeding
Low levels of white blood cells, which may make you more susceptible to infection
Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

fever
chills
infections
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
These are not all the possible side effects of CASGEVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of CASGEVY

Talk to your healthcare provider about any health concerns.

Please see full Prescribing Information including Patient Information for CASGEVY.

On June 14, 2024 enGene Holdings Inc. (Nasdaq: ENGN, "enGene" or the "Company"), a clinical-stage genetic medicines company whose non-viral, intravesical lead product candidate, EG-70, is in a pivotal study for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), reported its financial results for the second quarter ended April 30, 2024, and provided a business update (Press release, enGene, JUN 14, 2024, View Source [SID1234644349]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our $200 million private placement in February positioned us well to execute our primary strategy of broadly developing EG-70 to be a patient- and practice-friendly option across a multitude of potential bladder cancer indications. Correspondingly, our planned initial expansion of the LEGEND study will include a cohort focused on enrollment of patients with high-risk, BCG-unresponsive papillary-only NMIBC, a disease with persistent unmet need for which EG-70 may be well-suited," said Jason Hanson, Chief Executive Officer of enGene. "Furthermore, we plan to provide the interim data for the LEGEND BCG-unresponsive cohort by the end of September 2024. We believe the design of EG-70, with its ease-of-use and non-viral profile, positions it well to seamlessly slot into the standard of care, with the goal of becoming a practice-changing product that does not require a change in practice for urologists."

Anticipated Milestones and Strategic Corporate Updates

Release of interim data from LEGEND Cohort 1: The Company expects to release interim data from the LEGEND study’s BCG-unresponsive cohort by the end of September, comprised of responses from approximately 20 patients focused on the three- and six-month time points. Study enrollment remains ongoing, and based on current projections, enGene expects to file a Biologics License Application (BLA) for EG-70 in mid-2026.

Commitment to expanding the clinical development of EG-70 within the bladder: Building on the design of EG-70 to have category-leading ease of use, scalable manufacturing process, and low cost-of-goods, the Company plans to explore additional applications of EG-70 within the bladder by expanding the LEGEND study to include a third cohort targeting high-risk BCG-unresponsive papillary-only NMIBC patients and modifying the second cohort (previously, the BCG-naïve cohort) to include BCG-exposed patients. Collectively, these potential indications represent an expansion into several areas of persistent unmet medical need with substantial patient populations. These clinical development plans include:

Papillary-only LEGEND expansion: The Company plans to expand LEGEND to enroll a third cohort of patients with BCG-unresponsive, papillary-only Ta/T1 disease. This cohort, whose target enrollment is 70-100 patients, is estimated to begin enrollment in the fourth quarter of 2024.
Modification of the second cohort of LEGEND study to separately analyze responses between BCG-naïve patients and BCG-exposed patients: In anticipation of this planned cohort modification and expected corresponding engagement with FDA, enrollment has been temporarily paused in this second cohort, with enrollment in both groups expected to resume in the fourth quarter of 2024.
As a result of the prioritization of these potential new indications in bladder cancer, the Company has deprioritized pre-clinical development of EG-i08 for cystic fibrosis and has paused further activities on that program.

Key leadership hires and board additions: In May 2024, enGene announced the election of Paul Hastings and Wouter Joustra as new members of its Board of Directors at the Company’s 2024 annual meeting of shareholders. Lota Zoth was also re-elected to the Board. Each will serve a three-year term expiring at the 2027 annual meeting of shareholders. enGene’s Board is comprised of seven members including Richard Glickman (Chairman), Gerald Brunk, Jasper Bos, and enGene CEO, Jason Hanson.

In April 2024, the Company announced that Raj Pruthi MD MHA FACS joined the Company as SVP, Urologic Oncology and Clinical Development. Dr. Pruthi joined enGene from Johnson & Johnson Innovative Medicine, where he was most recently the Global Medical Affairs Leader, Bladder Cancer and Senior Medical Director, Oncology (Global – Prostate and Bladder Cancer).

Second Quarter 2024 Financial Results

Cash and cash equivalents, as of April 30, 2024, were $264.8 million. The Company expects that its existing cash and cash equivalents will fund operating expenses, debt obligations and capital expenditures into 2027.

Three Months ended April 30, 2024
Total operating expenses were $17.3 million for the three months ended April 30, 2024, compared to $4.7 million for the three months ended April 30, 2023. Research and development expenses increased by $6.6 million, mainly due to increasing manufacturing and clinical costs related to our pivotal EG-70 study. General and administrative expenses increased by $5.9 million, primarily driven by headcount costs and professional fees such as legal, accounting and audit as the Company scales its general and administrative function to support the operation of a public company.

For the three months ended April 30, 2024, net loss attributable to common shareholders was approximately $15.0 million, or $0.38 per share, compared to approximately $6.5 million, or $9.30 per share, for the same period for the three months ended April 30, 2023. The increase in net loss is mainly attributed to the increase in operating expenses partially offset by net interest income earned during the period.