The first patient has been dosed in the phase 1b KEYNOTE-B79 trial (NCT04991948) of the chimeric antigen receptor (CAR) T-cell therapy CYAD-101 (Celyad Oncology) in combination with pembrolizumab for refractory metastatic colorectal cancer (mCRC).

Further details on the trial were presented at the 

2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers (GI) Symposium, January 20-22, 2022

, by Richard D. Kim, MD, service chief, Medical Gastrointestinal Oncology and senior member, Gastrointestinal Oncology Department, Moffitt Cancer Center, and professor, oncology, University of South Florida College of Medicine.

“[Evidence implied] that CYAD-101 may also be modulating the immune suppressive environment in patients mirroring what was demonstrated in pre-clinical models. We considered that a sequential therapy with the anti-PD1 monoclonal antibody pembrolizumab to further release the anti-tumor potential of this expanded T-cell population may drive deeper, more durable and new clinical responses beyond that currently demonstrated with the CAR T-cells alone,” Kim and colleagues wrote.

KEYNOTE-B79 is evaluating the safety and efficacy of 3, bi-weekly, 1x10

-cell infusions of CYAD-101 after FOLFOX preconditioning across 5 sites in the US and Europe.Participants will start 200 mg pembrolizumab treatment 3 weeks after last infusion, which will continue every 3 weeks for up to 2 years. The trial is enrolling participants with microsatellite stable/mismatch-repair proficient, relapsed/refractory mCRC after at least 1 metastatic line of therapy that included FOLFOX chemotherapy.

Expanding the Use of CAR T Therapy With shRNA

The trial’s primary endpoints are evaluating safety and efficacy via the occurrence of dose-limiting toxicities (DLTs) and objective response rate (ORR). ORR will be evaluated 6 weeks after first pembrolizumab treatment.Preliminary data from the trial are expected in the second half of 2022.

Celyad Oncology is developing additional CAR T-cell therapies, including CYAD-211, an allogeneic shRNA-based anti-BCMA therapy for relapsed/refractory multiple myeloma, and CYAD-02, a next-generation, autologous NKG2D receptor therapy for acute myeloid leukemia and myelodysplastic syndrome.

Filippo Petti, chief executive officer, Celyad Oncology, commented on the company’s trials in a statement, saying, “The validation of our proprietary shRNA platform this past year represented an incredible achievement for the Company as we continued to strategically transform the organization to a fully allogeneic CAR T platform Company. The power and versatility of our shRNA platform, including the ability to multiplex and modulate the levels of gene expression, continues to support its strength, value, and potential differentiation within the allogenic cell therapy landscape. We believe our non-gene edited technologies are well-positioned to drive a major impact on the CAR T industry as the approach that does not have the risks associated with gene-editing technologies, including the potential for translocation adverse events.”

CYAD-211 is being evaluated in the phase 1/2 IMMUNICY-1 trial (NCT04613557), which has so far demonstrated clinical activity with an acceptable safety profile. The phase 2 portion of the study will evaluate lymphodepleting regimens with the cell therapy. Additional data is expected mid-2022. CYAD-02 is being evaluated in the phase 1 CYCLE-1 trial (NCT04167696) which has demonstrated that a single shRNA can target both 

“We believe our cutting-edge research in the allogeneic CAR T field supported by clinical data presented at multiple medical conferences over the past year and combined with these broader resources place us on an accelerated path towards developing the therapeutic benefit of our extensive set of technologies. This is an exciting time at Celyad Oncology and we look forward to building upon our recent accomplishments throughout 2022 and beyond,” Petti added to the statement.

1. Celyad oncology announces first patient dosed in KEYNOTE-B79 phase 1b trial. News release. Celyad Oncology. December 16, 2021. 

https://celyad.com/2021/12/16/celyad-oncology-announces-first-patient-dosed-in-keynote-b79-phase-1b-trial/


2. Kim RD, Prenen H, Rottey S, et al. KEYNOTE-B79 phase 1b trial to evaluate the allogeneic CAR T-cells CYAD-101 and pembrolizumab in refractory metastatic colorectal cancer patients. Presented at: 2022 ASCO GI Symposium. Poster #N10
3. Celyad Oncology provides outlook for 2022. News release. Celyad Oncology. January 10, 2022. https://www.businesswire.com/news/home/20220109005042/en/Celyad-Oncology-Provides-Outlook-for-2022

Articles

Further details on the KEYNOTE-B79 trial were presented at the 2022 ASCO GI Symposium. 

First Patient Dosed in CAR T-Cell Therapy/Pembrolizumab Trial for Colorectal Cancer

This content originally appeared on our sister site, 

spoke with Greg Kunst, chief executive officer, Aurion Biotech, at  the 

2021 American Academy of Ophthalmology annual meeting

 to learn more about the company's plans to initiate clinical trials of cell therapy for the potential treatment of corneal endothelial disease.

Aurion's lead cell therapy candidate is Vyznova, which has demonstrated safety, efficacy and tolerability in corneal endothelial disease in clinical trials in Japan. The company is preparing a new drug application for the cell therapy in Japan and will soon initiate clinical trials in the US.

 We presented on what could be a potential to be a major game change in the way that we treat corneal endothelial disease here in the United States around the world. We're doing this with cell therapy. Cell therapy could cure blindness and restore vision to potentially 16 million people in the US, Europe and Japan affected by corneal endothelial disease. It's a potential game changer for 4 simple reasons.

One, it's an injection of cells, and therefore can be used by a broad spectrum of ophthalmologists around the world, dramatically increasing the number of treaters available for corneal endothelial disease.

Two, it uses natural human endothelial cells, because of that, the safety profile is quite pristine, potentially allowing us to move this treatment earlier in the treatment paradigm.

Third, it's already been proven. We've done this drug now, in over 100 patients with some of those patients with 5 more years of experience in 4 different trials in Japan and in El Salvador. We know the drug works.

Fourth and most importantly, it scales. Unlike today, where we need a donor for every person treated for corneal endothelial disease, with every donor with a part in cell therapy, we get 100 treatments today. In the future, you know, 1 to 1,000, maybe 1 to 10,000. This all has all the hallmarks to be the really the next great innovation in ophthalmology.

We know there are about 13 million people around the world that are corneally blind. And usually one of the primary reasons that we see corneal blindness is the lack of available corneal tissue around the world. Even in the United States, we reserve corneal surgical transplant really for the worst patients. And because of this, we believe that we can reach many more patients with corneal endothelial disease, including Fuchs dystrophy or post keratopathy.

Certainly, it's an area where lots of people are untreated. In the future,  pending approval, we'll have a way to treat patients earlier in their disease.

So our next stage is to enter trials in the United States. Obviously the clinical trial process takes time. This is a rare technology because of the prior clinical data, generated in Japan and El Salvador, we know it works. Now it's the test of time of clinical trials, and at the end of these trials, we are hopeful, optimistic, that we'll be able to get approval from the FDA and many other regulators around the world.

Videos

Greg Kunst, chief executive officer, Aurion Biotech, discussed the potential of cell therapy in treating people with corneal endothelial disease around the world.

Improving Outcomes in Corneal Endothelial Disease With Cell Therapy

The cell and gene therapy sectors are growing exponentially, with new players emerging daily and much progress being made both in and out of the lab. 

 Around the Helix is your chance to catch up with the latest news in gene and cell therapies, including partnerships, pipeline updates, and more.

1. FDA Extends BLA Review for bluebird bio’s β-Thalassemia and CALD Gene Therapies

 for bluebird bio’s biologics license applications for its investigative gene therapies: betibeglogene autotemcelfor β-thalassemia and elivaldogene autotemcel for cerebral adrenoleukodystrophy to August 19, 2022, and September 16, 2022, respectively.

2. Celularity’s CYNK-101 Wins Fast Track Designation for HER2+ Gastric/GEJ Cancers

, a genetically modified natural killer cell therapy being developed by Celularity, in combination with standard frontline chemotherapy, trastuzumab (Herceptin), and pembrolizumab (Keytruda) for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. 

3. Gamida Cell on Track to Submit Omidubicel BLA in First Half of 2022

Gamida Cell is planning to complete their 

biologics license application for omidubicel

, a cell therapy for bone marrow transplant in patients with hematologic malignancies, in the first half of 2022 following positive Type B meeting correspondence from the FDA. The FDA had previously requested 

4. REGENXBIO Initiates ASCENT Trial of RGX-314 Wet AMD Gene Therapy

 of their subretinal gene therapy RGX-314 for the potential treatment of wet age-related macular degeneration. ATMOSPHERE (NCT04704921), the first trial to be initiated by REGENXBIO in collaboration with AbbVie, is currently active and screening patients.

5. Rubius Therapeutics Doses First Patient in Cell Therapy Trial for Solid Tumors

, an allogeneic, cell therapy candidate expressing 4-1BBL and IL-12, for the potential treatment of relapsed/refractory or locally advanced solid tumors, including non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial carcinoma and triple-negative breast cancer.

6. Atara and Imeka Collaborating to Use Advanced Imaging in MS Cell Therapy Trial

Atara Biotherapeutics will use Imeka’s proprietary biomarker imaging technology in the phase 2 EMBOLD trial (NCT03283826) assessing ATA188 as a monotherapy in multiple sclerosis. Atara hopes to use the imaging technology to further 

analyze the effects of ATA188 on neuroinflammation

7. Mesoblast’s Cell Therapy Reduces Chronic Low Back Pain

Mesoblast’s allogeneic cell therapy rexlemestrocel-L (MPC-06-ID) reduced chronic low back pain associated with degenerative disc disease, according to 

 from their 404-patient phase 3 trial (NCT02412735). The cell therapy will be assessed in an additional phase 3 trial.

8. BlueRock Therapeutics Doses First Patient in Phase 1 Cell Therapy Trial in Parkinson Disease

 in a phase 1, open-label trial (NCT04802733) of MSK-DAO1, BlueRock’s pluripotent stem cell-derived dopaminergic neuron cell therapy in patients with advanced Parkinson disease.

9. Longeveron Publishes Trial Design for Frailty in Aging Cell Therapy

The phase 2b trial will assess Lomecel-B, a living cell therapy product, as a regenerative medicine for the potential treatment of aging frailty. The 

design and rationale of the study was published

10. Tevogen Granted Patent for SARS-CoV-2 T-Cell Therapy Preparation

 for their method of preparing and manufacturing TVGN-489, a COVID-19 peptide specific cytotoxic T cell therapy. The cell therapy is designed to target the entire SARS-CoV-2 viral genome rather than only spike proteins.

11. Intellia Doses First Patient With ATTR Amyloidosis and Cardiomyopathy in New Gene Therapy Trial Cohort

The phase 1 trial (NCT04601051) of NTLA-2001, an investigational CRISPR gene editing therapy delivered with Intellia’s lipid nanoparticle technology for the treatment of ATTR amyloidosis, recently added a cardiomyopathy arm which has 

. Intellia expects the trial, which continues to evaluate NTLA-2001 in patients with hereditary ATTR amyloidosis with polyneuropathy, to complete enrollment in 2022.

1. bluebird provides update on FDA review timelines for betibeglogeneautotemcel (beti-cel) for beta-thalassemia and elivaldogeneautotemcel (eli-cel) for cerebral adrenoleukodystrophy (CALD). News release. bluebird bio. January 18, 2022. 

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-provides-update-fda-review-timelines-betibeglogene


2. Celularity receives fast track designation from U.S. FDA for its NK cell therapy CYNK-101 in development for the first-line treatment of advanced HER2/neu positive gastric and gastroesophageal junction cancers. News release. Celularity. January 18, 2022. Accessed January 18, 2022. 


3. Gamida Cell provides update on omidubicel BLA submission. News release. Gamida Cell. January 19, 2022. 

https://www.yahoo.com/now/gamida-cell-provides-omidubicel-bla-120000727.html


4. Gamida Cell Provides Update on Pre-BLA Meeting With FDA for Omidubicel. News release. Gamida Cell. News release. November 11, 2021. 

https://www.businesswire.com/news/home/20211111005505/en/Gamida-Cell-Provides-Update-on-Pre-BLA-Meeting-With-FDA-for-Omidubicel


5. REGENXBIO announces initiation of second pivotal trial in RGX-314 clinical program for the treatment of wet AMD using subretinal delivery. News release. REGENXBIO. January 10, 2022. 

https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-initiation-second-pivotal-trial-rgx-314


6. Rubius Therapeutics announces dosing of first patient in phase 1/2 trial of RTX-224, a broad immune agonist, for the treatment of certain solid tumors. News release. Rubius Therapeutics. January 13, 2022. 

https://www.biospace.com/article/releases/rubius-therapeutics-announces-dosing-of-first-patient-in-phase-1-2-trial-of-rtx-224-a-broad-immune-agonist-for-the-treatment-of-certain-solid-tumors/?s=107


7. Imeka collaborates with Atara Biotherapeutics to provide neuroimaging for phase 2 study in multiple sclerosis. News release. Imeka. January 11, 2022. 

https://www.prnewswire.com/news-releases/imeka-collaborates-with-atara-biotherapeutics-to-provide-neuroimaging-for-phase-2-study-in-multiple-sclerosis-301457246.html


8. Single dose of Mesoblast’s allogeneic cell therapy provides durable pain reduction for at least three years in patients with degenerative disc disease 36-Month results of phase 3 trial in chronic low back pain presented at 2022 biotech showcase. News release. Mesoblast. January 12, 2022. 

https://www.biospace.com/article/releases/single-dose-of-mesoblast-s-allogeneic-cell-therapy-provides-durable-pain-reduction-for-at-least-three-years-in-patients-with-degenerative-disc-disease36-month-results-of-phase-3-trial-in-chronic-low-back-pain-presented-at-2022-biotech-showcase/?s=69


9. BlueRock Therapeutics announces first patient dosed in Canada in phase 1 trial in patients with advanced Parkinson's disease. News release. BlueRock Therapeutics. January 18, 2022. 

https://finance.yahoo.com/news/bluerock-therapeutics-announces-first-patient-130000024.html


10. Longeveron announces publication of Lomecel-B phase 2b trial design in Journal of Frailty and Aging. News release. Longeveron. January 12, 2022. 

https://www.biospace.com/article/releases/longeveron-announces-publication-of-lomecel-b-phase-2b-trial-design-in-journal-of-frailty-and-aging/


11. Tevogen Bio™ further strengthens IP portfolio with additional patent for method of preparing its investigational SARS-CoV-2 specific T cell therapy. News release. Tevogen Bio. January 12, 2022. 

https://www.businesswire.com/news/home/20220112006056/en/Tevogen-Bio%E2%84%A2-Further-Strengthens-IP-Portfolio-With-Additional-Patent-for-Method-of-Preparing-Its-Investigational-SARS-CoV-2-Specific-T-cell-Therapy


12. Intellia Therapeutics highlights strategic priorities and anticipated development milestones for 2022. News release. Intellia Therapeutics. January 6, 2022. https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-highlights-strategic-priorities-and-0

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in gene and cell therapies.  

Around the Helix: Gene and Cell Therapy Company Updates - January 19, 2022 

Eureka Therapeutics has initiated the phase 1/2 ARYA-2 trial (NCT04634357) of the ET140203 ARTEMIS T-cell therapy in pediatric patients with relapsed or refractory 

 (HB), hepatocellular neoplasm not otherwise specified (HCN-NOS), or hepatocellular carcinoma (HCC).

“Relapsed or refractory pediatric liver cancers are rare, have limited treatment options, and remain difficult to treat,” principal investigator Allison F. O'Neill, MD, clinical director, Solid Tumor Program, and director, Medical Therapies, Liver Tumor Center of Excellence, Dana-Farber/Boston Children’s, said in a statement.

 “Engineered T-cell therapies have the potential to transform the outcome of patients with difficult-to-treat liver cancers. We are thrilled to work with Eureka Therapeutics and initiate a trial of ET140203 T-cell therapy for pediatric and adolescent patients with relapsed or refractory liver tumors.”

The phase 1 portion of the open-label, dose escalation, multi-center ARYA-2 trial is now open for enrollment at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The ARYA-2 trial is being run in parallel with the phase 1/2 ARYA-1 (NCT04502082) trial that commenced in October 2020 and the phase 1/2 ARYA-3 (NCT04864054) trial that commenced in July 2021, both of which are evaluating T-cell therapies in adult patients with HCC. The ARYA-1 and ARYA-2 trials are evaluating ET140203 targeted toward the AFP-peptide/HLA-A2 complex while ARYA-3 is evaluating the ECT204 T-cell therapy targeted toward the GPC3 protein.

Eureka’s cell therapies are developed using their ARTEMIS platform, whichuses proprietary tumor infiltration technology designed to enhance the ability of cell therapies to infiltrate solid tumors. The approach has shown efficacy in animal models. The FDA previously granted ET140203 fast track designation for the treatment of HB and HCC in pediatric patients as well as rare pediatric disease designation for the treatment of HB.

Celularity’s CYNK-101 Wins Fast Track Designation for HER2+ Gastric/GEJ Cancers

“Eureka recognizes the highly unmet medical need in treating pediatric patients with advanced liver cancers,” Cheng Liu, PhD, founder, president, and chief executive officer, Eureka Therapeutics, added to the statement.

 “We are pleased to be working with Dana-Farber to address it by bringing ARTEMIS® T-cell therapies to patients in the clinics.”

Eureka Therapeutics has other ventures in treating solid tumors; in November 2021, the company announced a collaboration with Imugene

 which will evaluateImugene’s CD19 onCARlytics oncolytic virus technology in combination with Eureka's anti-CD19 T-cell therapies. The approach previously demonstrated efficacy in preclinical studies in mouse models conducted by the City of Hope Comprehensive Cancer Center.

“We are delighted to be working with Imugene on tackling solid tumours using this innovative approach,” Liu said in a previous statement.

 “We believe our ARTEMIS® T-cell platform to be the ideal one to evaluate this combination. In head-to-head pre-clinical studies against CAR-T cells, our ARTEMIS® T-cells demonstrated superior efficacy, enhanced tumour infiltration, and less T-cell exhaustion. In the clinical context, our ARTEMIS® T-cells have demonstrated reduced cytokine release syndrome and other cytokine-related toxicities compared to CAR-T cells, potentially improving the efficacy and safety of a combination approach.”


1. Eureka Therapeutics announces initiation of phase I/II ARYA-2 clinical trial of ET140203 ARTEMIS® T cells to treat pediatric liver cancer. News release. New release. Eureka Therapeutics. November 18, 2021. 

https://pipelinereview.com/index.php/2021111879731/DNA-RNA-and-Cells/Eureka-Therapeutics-Announces-Initiation-of-Phase-I/II-ARYA-2-Clinical-Trial-of-ET140203-ARTEMIS-T-Cells-to-Treat-Pediatric-Liver-Cancer.html


2. Imugene and Eureka Therapeutics announce strategic collaboration to accelerate advancement of oncolytic virus and T-cell therapy in solid tumours. News release. Eureka Therapeutics. November 1, 2021. https://www.eurekatherapeutics.com/media/press-releases/110121/

The phase 1/2 ARYA-2 trial will be run in parallel with the similar phase 1/2 ARYA-1 and ARYA-3 trials. 

Trial Initiated for Pediatric Liver Cancer Cell Therapy

“In my mind, these [data from CARTITUDE-1] were the best results that have ever been shown in this truly triple-class refractory, 6 prior lines of therapy population. This is the most aggressive and the most responsive and efficacious therapy, as a single agent in refractory multiple myeloma treatment, that we've ever seen.”

Ciltacabtagene autoleucel (cilta-cel) produced deep and durable responses in heavily-pretreated patients with multiple myeloma, according to data from the phase 1/2 CARTITUDE-1 study (NCT03548207) presented at the 

63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021

, by Thomas G. Martin, MD, clinical professor of medicine, Adult Leukemia and Bone Marrow Transplantation Program, and associate director, Myeloma Program, University of California San Francisco, and co-leader, Cancer Immunology & Immunotherapy Program, Helen Diller Family Comprehensive Cancer Center.

Investigators found that the 97 participants treated with cilta-celin the CARTITUDE-1 study had an overall response rate of 98% and that of 61 evaluable participants with minimal residual disease, the progression-free survival rate at 2 years was 100%. Also presented at ASH 2021 were positive results in a less-pretreated population.

 spoke with Martin to learn more about the data from CARTITUDE-1 presented at ASH 2021. He discussed the positive results and cilta-cel's potential in this population.

1. New data from CARTITUDE-1 Study show continued deep and durable responses of ciltacabtageneautoleucel (cilta-cel) in treatment of heavily pretreated patients with multiple myeloma. News release. Janssen. December 12, 2021. 

https://www.janssen.com/new-data-cartitude-1-study-show-continued-deep-and-durable-responses-ciltacabtagene-autoleucel-cilta


2. Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: Phase 1b/2 study of CiltacabtageneAutoleucel, a B-cell maturation antigen–Directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 549.
3. Jakubowiak A, Usmani SZ, Berdeja JG, et al. Efficacy and safety of ciltacabtageneautoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 subgroup analysis. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 3938.

The clinical professor of medicine, Helen Diller Family Comprehensive Cancer Center, UCSF, discussed data from the CARTITUDE-1 study presented at ASH 2021. 

Cilta-Cel's Efficacy in Heavily Pretreated Patients With Multiple Myeloma: Thomas G. Martin, MD 

The FDA has extended the review dates for bluebird bio’s biologics license applications (BLAs) for its investigative gene therapies: betibeglogene autotemcel (beti-cel) for β-thalassemia and 

 for cerebral adrenoleukodystrophy (CALD).

The FDA extended each of the reviews by 3 months, moving beti-cel's PDUFA date from May 20, 2022, to August 19, 2022, and eli-cel's from June 17, 2022, to September 16, 2022. The extension is intended to give the FDA time to review new clinical information received from bluebird in response to previous information requests.

“Gene therapies are complex, potentially transformative treatment options for those living with severe genetic diseases, and we all share a responsibility to be diligent for patients as we progress this novel field,” Andrew Obenshain, chief executive officer, bluebird bio, said in a statement.

 “We look forward to continuing to work with the FDA on its ongoing reviews of beti-cel and eli-cel, and to bringing these therapies to patients with β-thalassemia and CALD in the US later this year.”

 in November 2021 for patients with β-thalassemia across all genotypes who require regular blood transfusions.

 The submission was based on data from the phase 3 studies HGB-207 (Northstar-2; NCT02906202) and HGB-212 (Northstar-3; NCT03207009), the Phase 1/2 HGB-204 (Northstar; NCT01745120) and HGB-205 (NCT02151526) studies, and the long-term follow-up study LTF-303 (NCT02633943).

The State of Gene and Cell Therapy for Sickle Cell Disease

Data from the LTF-303 trial were presented at the 

 that demonstrated the gene therapy candidate’s durable effect in β-thalassemia.

 Three previously transfusion-dependent participants exhibited normal or near-normal levels of total hemoglobin and have remained transfusion-free with stable iron markers through up to 7years of follow-up.

bluebird's BLA for eli-cel for the potential treatment of CALD was 

The BLA submission was based on efficacy and safety data from 32 participants in the completed Phase 2/3 Starbeam study (ALD-102; NCT01896102) and 23 participants in the Phase 3 ALD-104 study (NCT03852498), in which follow-up is ongoing. An additional long-term follow-up study (LTF-304; NCT02698579) is ongoing.

Beti-cel and eli-cel, if approved, would be the first lentiviral vector gene therapies for patients with severe genetic diseases to enter the market. While lentiviral vectors are certainly a promising avenue for gene therapy, bluebird bio has run into more than their share of trouble with the vectors, with their programs put on multiple clinical holds in 2021.

Clinical holds were lifted in June 2021 on programs that use the lentiviral vector BB305, including their phase 1/2 HGB-206 and phase 3 HGB210 trials of lovotibeglogene autotemcel (lovo-cel) for SCD as well as the HGB-207 and HGB-212 studies for β-thalassemia.

Just 6 months later in December 2021, the lovo-cel program was placed and remains on 

 following a report of persistent anemia in an adolescent patient.

 The patient is doing clinically well, with no evidence of malignancy or clonal predominance. bluebird has received written questions from the FDA and will update the public in February 2022 if they no longer expect a BLA submission in the first quarter of 2023.

“The safety of patients treated with our gene therapies is always our top priority,” Richard Colvin, MD, chief medical officer, bluebird bio said in a statement.

 “Consistent with the FDA’s direction, we have paused enrollment and treatment of patients younger than 18 in our SCD clinical program, and we will continue to work collaboratively with the FDA to understand and address their concerns.”

 since August 2021 following the Suspected Unexpected Serious Adverse Reaction (SUSAR) of MDS in the ALD-104 study thought to be mediated by the use of their lentiviral vector.

 Two other cases of MDS have been reported in participants treated with eli-cel and treated participants are being closely monitored.

“Eli-cel is an important potential therapeutic option for patients with CALD—a devastating neurodegenerative disease—and we are encouraged to be moving forward given the urgent unmet need for these children and their families,” Obenshain said in a previous statement.


2. bluebird bio Announces FDA Priority Review of Biologics License Application for beti-cel Gene Therapy for Patients with β-thalassemia Who Require Regular Red Blood Cell Transfusions. News release. bluebird bio. November 22, 2021. 

https://www.biospace.com/article/releases/bluebird-bio-announces-fda-priority-review-of-biologics-license-application-for-beti-cel-gene-therapy-for-patients-with-%CE%B2-thalassemia-who-require-regular-red-blood-cell-transfusions/


3. Thompson AA, Locatelli F, Yannaki E, et al. Restoring Iron Homeostasis in Pts Who Achieved Transfusion Independence after Treatment with Betibeglogene Autotemcel Gene Therapy: Results from up to 7 Years of Follow-up. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 573.
4. bluebird bio announces FDA priority review of biologics license application for eli-cel gene therapy for cerebral adrenoleukodystrophy (CALD) in patients without a matched sibling donor. News release. bluebird bio. December 17, 2021. 

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-fda-priority-review-biologics-license-0


5. bluebird bio announces the lifting of FDA clinical hold for sickle cell disease and β-Thalassemia studies. News release. bluebird bio. June 7, 2021. 

https://www.businesswire.com/news/home/20210607005267/en/bluebird-bio-Announces-the-Lifting-of-FDA-Clinical-Hold-for-Sickle-Cell-Disease-and-%CE%B2-Thalassemia-Studies


6. bluebird bio Announces Partial Clinical Hold for Patients Under 18 in Sickle Cell Gene Therapy Clinical Program. News release. bluebird bio. December 20, 2021. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-partial-clinical-hold-patients-under-18
7. bluebird bio reports second quarter financial results and provides operational update. News release. bluebird bio. August 9, 2021. https://www.businesswire.com/news/home/20210809005334/en/bluebird-bio-Reports-Second-Quarter-Financial-Results-and-Provides-Operational-Update

Eli-cel remains on clinical hold in cerebral adrenoleukodystrophy after a report of persistent anemia. 