Clinical Trial Updates (SCD)

Gene Therapy

Update: 30 June 2022

  • More than half of the patients in the HGB-210 study that will be needed to support manufacturing data requirements for the lovotibeglogene autotemcel (lovo-cel) biologics licensing application (BLA) have been enrolled.
  • BLA submission to the FDA for sickle cell disease (SCD) is anticipated in the first quarter of 2023.
  • As previously communicated, the Company has treated all patients in HGB-206 Group C who will form the primary basis of efficacy for BLA submission, with the demonstration of analytical comparability and validation of the commercial manufacturing process as the key remaining actions prior to submission (to be completed by end of 2022) of the planned BLA.

Source: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-first-quarter-2022-financial-results-and

 

Update: 25 April 2022

No update available

 

Update: 10 January 2022

  • The FDA has placed the clinical program for lovotibeglogene autotemcel (lovo-cel) gene therapy for sickle cell disease (SCD) on partial clinical hold for patients under the age of 18.
  • The partial, temporary suspension relates to an ongoing investigation by bluebird bio into an adolescent patient with persistent, non-transfusiondependent anaemia following treatment with lovo-cel, now 18 months post treatment. This patient is clinically well and there is no evidence of malignancy or clonal predominance.
  • Enrollment and dosing for patients 18 and older living with SCD in the HGB-206, HGB-210, and LTF-307 clinical studies, as well as follow-up for treated patients of all ages in all studies are continuing as planned.
  • Consistent with the FDA’s clinical hold procedures, bluebird anticipates receiving written questions from the agency in early 2022 and will work quickly to respond in order to resolve the partial hold. The company is evaluating what impact, if any, the partial clinical hold may have on first quarter 2023 projected timing for the lovo-cel biologics license application (BLA) submission.
  • Data of the clinical trials on SCD with cut-off date of February 17, 2021, were presented at ASH2021. These showed that 49 patients have been treated with lovo-cel with up to six years of patient follow-up (median: 24 months) across the HGB-205 (n=3), HGB-206 (n=44), and HGB-210 (n=2) clinical studies, representing more than 109 total patient-years of data. The Phase 1/2 HGB-206 trial includes Groups A (n=7), B (n=2), and C (n=35), reflecting progressive adaptations to the treatment and manufacturing processes.
  • Data of HGB-206 Group C presented at ASH2021 showed that patients with SCD maintain a median haemoglobin of ≥ 11g/dl for more than 6 months post-treatment; notably, sickle hemoglobin (HbS) in all patients was less than 60% of total hemoglobin, and gene therapy-derived anti-sickling hemoglobin, HbAT87Q, contributed at least 40% of total hemoglobin. All evaluable patients (n=25) continued to experience complete resolution of severe VOEs through up to 36 months of follow-up.
  • The ongoing phase 1/2 HGB-206 study is evaluating the efficacy and safety of LentiGlobin for SCD (bb1111) gene therapy and has demonstrated complete resolution of severe VOEs, near-normalization of key hemolysis markers, and normalization of total hemoglobin up to 24 months post-LentiGlobin infusion in Group C. Data presented at ASH2021 on patient-reported QoL outcomes up to 24 months post-infusion indicate meaningful change using the PROMIS-57 of assessment of patient physical, mental and social well-being.
  • A comparison of the biological outcomes, clinical outcomes, and clonality between the initial cohort (Group A) and the cohort treated after study protocol and manufacturing process changes (Group C) in the phase 1/2 HGB-206 study were presented at ASH2021. This data showed that alterations to the protocol and manufacturing process resulted in improved cell dose, transduction efficiency, HbAT87Q expression, and clinical outcomes in Group C compared with Group A. Furthermore, superior engraftment leads to favorable clinical outcomes.
  • Real-world evidence was presented at ASH2021 including a comparison of the severe acute complications of SCD experienced by patients in two expert centres (v. Royal London Hospital and the University of Padova) which showed that even where patients receive expert care in accordance with international guidelines, VOC’s continue to be experienced thus necessitating the development of more disease-modifying therapies (in addition to HU and CTT) as well as curative therapies.

Sources: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bioannounces-partial-clinical-hold-patients-under-18
https://investor.bluebirdbio.com/news-releases/news-release-details/new-andupdated-data-demonstrating-sustained-treatment-response
Walters M et al, ASH2021, Oral Presentation – https://ash.confex.com/ash/2021/webprogram/Paper146905.html
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Tisdale JF et al, ASH2021, Oral Presentation – https://ash.confex.com/ash/2021/webprogram/Paper147760.html
Colombatti, R et al, Poster Presentation – ASH2021; Blood, Nov.2021 –https://www.sciencedirect.com/science/article/abs/pii/S0006497121050278

 

Update: 27 October 2021

No update available

 

Update: 30 June 2021

  • Phase 1/2 (HGB-206) and Phase 3 (HGB-210) studies of LentiGlobin gene therapy for sickle cell disease (SCD) (bb1111) were placed on a temporary suspension due to a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) and MDS.
  • The first patient was infused in HGB-210, a Phase 3 confirmatory study of LentiGlobin™gene therapy (bb1111) for adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD).
  • The analyses completed until March 2021, indicated that it is very unlikely the Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) was related to the lentiviral vector. Laboratory analyses showed that the patient had significant chromosomal abnormalities and mutations in genes typically associated with the development of AML.
  • The case of MDS in a patient from Group C of the Phase 1/2 HGB-206 study of LentiGlobin gene therapy for SCD has been further assessed following the review of results from additional tests. The treating investigator has concluded this is not a case of MDS and has revised the diagnosis to transfusion-dependent anemia.
  • The US Food and Drug Administration (FDA) has lifted the clinical holds on the Phase 1/2 HGB-206 and Phase 3 HGB-210 studies of LentiGlobin for sickle cell disease (SCD) gene therapy (bb1111) for adult and pediatric patients with SCD.

Data of HGB-206 Group C presented at EHA2021 showed that patients with SCD maintain a median haemoglobin of ≥ 11g/dl for more than 6 months post-treatment with a complete reduction of VOC’s in up to 24 months of follow up.

Sources: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-temporary-suspension-phase-12-and-phase-3

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-fourth-quarter-and-full-year-2020-financial

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-provides-updated-findings-reported-case-acute

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-provides-update-severe-genetic-disease-programs-and

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-present-data-its-severe-genetic-disease-and

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-lifting-fda-clinical-hold-sickle-cell

EHA2021: Complete Resolution of Severe Vaso-Occlusive Events and Improved Pathophysiology with LentiGlobin Gene Therapy in Sickle Cell Disease (SCD): Ongoing Phase 1/2 HGB-206 Group C Study

http://investor.bluebirdbio.com/news-releases/news-release-details/treatment-investigational-lentiglobintm-gene-therapy-sickle-cell

http://investor.bluebirdbio.com/news-releases/news-release-details/magenta-therapeutics-and-bluebird-bio-announce-phase-2-clinical

 

Update: 08 January 2021

New data from the ongoing study of investigational LentiGlobin™ gene therapy (bb1111) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up

Group C Phase 1/2 HGB-206 for adult and adolescent patients with sickle cell disease (SCD) results presented at ASH2020:

  • 32 patients with up to 30.9 months of follow-up.
  • In 22 patients with six or more months of follow-up, median levels of gene therapy- derived anti-sickling hemoglobin, HbAT87Q, contribute at least 40% of total haemoglobin.
  • At last visit reported, total hemoglobin ranged from 6  –  15.1  g/dL  and  HbAT87Q levels ranged from 2.7 – 8.9 g/dL.
  • Median HbS was 50% and remained less than 60% at all follow-up tmepoints.
  • All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.
  • 19 patients with a history of severe VOEs had a complete resolution of VOEs after Month 6.
  • One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.
  • Collaboration with Magenta Therapeutics has been announced to evaluate the utility of MGTA-145 for Mobilizing and Collecting Stem Cells in Adults and Adolescents with Sickle Cell Disease. MGTA-145 in combination with plerixafor (the so far preferred mobilization regimen) has shown in a Phase 1 study that it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. Thus potentially allowing for safer and more efficient mobilization for gene therapy to treat sickle cell disease thus achieving safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/treatment- investigational-lentiglobintm-gene-therapy-sickle-cell http://investor.bluebirdbio.com/news-releases/news-release-details/magenta- therapeutics-and-bluebird-bio-announce-phase-2-clinical

 

Update: 05 November 2020

BIOLOGICS LICENSE APPLICATION (BLA) SUBMISSION: Estimated to be completed in late-2022 as the FDA has requested the clinical data package be based on the HGB-26 study Group C cohort as well as comparable data between healthy donors, SCD patients and the commercial lentiviral vector.

EUROPEAN MEDICINES AGENCY: LentiGlobin for SCD has been granted eligibility for the EMA Priority Medicines programme and therefore PRIME designation enabling more speedy regulatory evaluations.

FOOD AND DRUG ADMINISTRATION: LentiGlobin for SCD has received orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation.

Sources: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-third-quarter-2020-financial-results-and

http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bios-lentiglobintm-sickle-cell-disease-gene-therapy

Update: 30 June 2022

New data was presented at EHA2022 from the ongoing Phase 1/2 MOMENTUM study to evaluate the safety and efficacy of ARU-1801, which is administered following reduced-intensity conditioning (RIC) and has demonstrated clinically meaningful improvements with drug product vector copy number (DP VCN) at and below 1.

Adults (18-45 years old) with severe SCD (as defined by recurrent vaso-occlusive events [VOE] and acute chest syndrome) were screened for eligibility. Prior to infusion of ARU-1801, all patients received a single IV dose of RIC melphalan (140 mg/m2 ). Endpoints included measures of melphalan pharmacokinetics, safety, engraftment, peripheral blood (PB) VCN, haemoglobin, and SCD-related outcomes

As of Feb 1, 2022, five patients (mean age [range], 26 [19-35] years old) have been treated with ARU-1801 gene therapy for SCD. Transient thrombocytopenia and neutropenia lasted a mean of 6 and 8 days, respectively. There have been no other serious adverse events related to chemotherapy or ARU-1801 to date

Preliminary data suggest ARU1801 achieves stable, high engraftment of transduced HSCs even in the setting of RIC, resulting in robust long-term maintenance of therapeutic haemoglobin levels

Sources: https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.eha/temp/eha22_abstract_bodies/P1453.html.pdf

 

Update: 25 April 2022

No update available

 

Update: 10 January 2022

New data presented at the ASH2021 showed the autologous CD34+ hematopoietic stem cell therapy has resulted in significant improvements in annualized vaso occlusive events, stabilized anti-sickling globins (HbF) and no treatment-related serious adverse events in 4 treated patients between the ages of 19 and 35. Data on three patients that had more than 12 months follow-up were presented.

Amelioration of SCD phenotype and engraftment of ARU-1801 gene-modified HSCs is possible with a single reduced-intensity conditioning (RIC) dose of melphalan, as demonstrated in three patients. RIC could lessen toxicities and resource utilization relative to myeloablative approaches, allowing expanded access to gene therapy for a broader group of SCD patients.

The first patient showed 27% HbF expression at three years and 93% reduction in VOEs. The second patient had lower HSC engraftment due to below-target melphalan exposure (likely caused by renal hyperfiltration), with 14% HbF and 5% HbA2 at three years. Nonetheless, an 85% reduction in VOEs in Patient 2 demonstrates significant
clinical benefit. Following manufacturing process improvements, the third patient has shown the highest HbF (36%) at one year, the highest F-cells (96%), and no VOEs since receiving ARU-1801.

ARU-1801, with RIC melphalan conditioning, is a promising alternative to myeloablative transplants for achieving durable responses with a favorable safety profile in patients with severe SCD.

Sources: https://www.hcplive.com/view/how-covid-19-is-informing-influenza-strategies
Grimley M et al. ASH2021 Poster Presentation – https://ash.confex.com/ash/2021/webprogram/Paper147469.html

 

Update: 27 October 2021

No update available

 

Update: 30 June 2021

  • The European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to ARU-1801. ARU-1801 was designated PRIME status based on clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, that demonstrate meaningful, durable reductions in disease burden.

Unlike investigational gene therapies and gene editing approaches which require fully myeloablative conditioning, the unique characteristics of ARU-1801 allow it to be given with reduced intensity conditioning (“RIC”). Compared to myeloablative approaches, the lower dose chemotherapy regimen underlying RIC has the potential to reduce not only hospital length of stay, but also the risk of short- and long-term adverse events such as infection and infertility. Preliminary clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, demonstrate continuing durable reductions in disease burden.

  • Three patients with sickle cell disease who received the investigational gene therapy ARU-1801 achieved and maintained normal hemoglobin levels, according to early results of a phase 1/phase 2 trial.

Sources: https://www.prnewswire.com/news-releases/aruvant-announces-the-european-medicines-agency-ema-granted-priority-medicines-prime-designation-to-aru-1801-for-the-treatment-of-sickle-cell-disease-301220542.html

https://www.healio.com/news/hematology-oncology/20210517/gene-therapy-for-sickle-cell-disease-shows-curative-potential?utm_source=selligent&utm_medium=email&utm_campaign=news&M_BT=5557136223742

 

Update: 08 January 2021

No update available

 

Update: 05 November 2020

Data will be presented at ASH2020 in December 2020 from the MOMENTUM study – an open-label Phase 1/2 clinical trial examining ARU-1801 as a one-time potentially curative gene therapy for individuals with sickle cell disease (SCD).

Unlike other investigational gene therapies that require fully myeloablative conditioning, ARU-1801 is given with reduced intensity conditioning (RIC), which is a lower dose chemotherapy.

Source: https://www.prnewswire.com/news-releases/aruvant-announces-updated-data-to-be-presented-in-oral-presentation-of-aru-1801-data-at-the-62nd-american-society-of-hematology-ash-annual-meeting-301166554.html

 

Update: 25 August 2020

No update available.

 

Update: 31 May 2020

No update available.

 

Update: 31 March 2020

No update available.

 

Update: 31 January 2020

The U.S. Food and Drug Administration (FDA) granted rare pediatric disease designation to ARU-1801, an experimental gene therapy for the treatment of sickle cell disease (SCD) and β-thalassaemia.

This designation means eligibility for a  priority review voucher once the FDA approves a biologics license application for ARU-1801.

Focus on delivering a modified version of the fetal haemoglobin gene, through a viral virus called lentivirus — optimized to enhance the protein’s natural oxygen-carrying ability and anti-sickling properties.

Source: https://sicklecellanemianews.com/2020/01/09/aravant-sickle-cell-therapy-gets-fda-rare-pediatric-disease-designation/

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