CGTLive's Pillars of Progress 2023: Top News in Hematology

For all of 2023, the CGTLive^™ team was following along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page.

Among our areas of focus in 2023 has been hematology, a field that saw several key approvals, as well as other treatments move through the pipeline. The major news items appeared among the top pieces our team produced—but sometimes smaller stories reach those heights as well because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in hematology over the course of 2023.

Here, we'll highlight some of the most-read content on CGTLive's hematology page this year. Click the buttons to read further into these stories.

1. FDA Experts Weigh in on Exa-Cel and Lovo-cel Approvals for Sickle Cell and Corresponding Black Box Safety Warnings

• Bluebird's lovo-cel, approved for sickle cell disease, showed efficacy, but a black box warning reflects myeloid malignancy risk.
• Vertex and CRISPR's gene therapy for sickle cell disease, Exa-cel, secured FDA approval without a black box warning.
• Both therapies require 15-year follow-ups, with safety concerns addressed, and ongoing evaluation for potential curative impact.

December 8, 2023 — On Friday, December 8, 2023, the FDA made a landmark decision to approve a pair of gene therapies for the treatment of sickle cell disease (SCD)—bluebird bio’s lovotibeglogene autotemcel (lovo-cel), marketed as Lyfgenia; and Vertex and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel), which is to be marketed under the name Casgevy.

"Both therapies that were approved today, through slightly different mechanisms, do decrease the number of vaso-occlusive events and have the potential to take a [patient with sickle cell] who has had several of these events to not have any of these events."

– Nicole Verdun, MD, of FDA CBER

2. CARTITUDE-4 Data Leak Reveals Promising Results for Cilta-Cel in Multiple Myeloma

• Leaked phase 3 data reveal a 74% reduction in multiple myeloma progression risk with CAR-T therapy.
• Positive findings could shift ciltacabtagene's use to first-line treatment, marking a paradigm shift in care.
• Full results of the CARTITUDE-4 trial were presented at European Hematology Association and ASCO meetings.

April 19, 2023 — Among individuals with relapsed and lenalidomide-refractory multiple myeloma (MM), ciltacabtagene autoleucel (Carvykti; Johnson & Johnson/Legend Biotech) has outperformed expectations compared with standard chemotherapy regimens—such as pomalidomide, bortezomib and dexamethasone; or daratumumab, pomalidomide and dexamethasone—according to leaked data from the phase 3 CARTITUDE-4 trial (NCT04181827) obtained by STAT News.

3. FDA Approves Omidubicel to Reduce Infection Risk in Patients With Hematologic Malignancies Undergoing Stem Cell Transplant

• Gamida Cell's allogeneic cell therapy reduces infection risk in hematologic cancer patients undergoing stem cell transplantation.
• Omidubicel, delivered as a single infusion, accelerates white blood cell recovery, reducing serious infection risks.
• Phase 3 trial shows omidubicel's faster recovery, lower infection risk, and improved quality of life.

April 17, 2023 — The FDA has approved Gamida Cell's allogeneic cell therapy, omidubicel, to reduce the risk of infection in patients aged 12 years and older undergoing stem cell transplantation for hematologic cancer. Omidubicel, which will be marketed as Omisirge, is delivered as a single intravenous infusion composed of patient-specific human allogeneic cord blood-derived stem cells that have been processed and cultured with nicotinomide, a form of vitamin B3.

“Today’s approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation."

– Peter Marks, MD, PhD, of the FDA

4. bluebird's HGB-210 Trial Hopes to Support First SCD Gene Therapy Approval

• There will be complexities with access and delivery of gene therapy to patients with sickle cell but the therapy has the potential to transform the treatment landscape.
• The ongoing trial evaluates single-dose lovo-cel's efficacy in patients aged 2-50, focusing on resolution of vaso-occlusive events.
• Phase 1/2 trials showcase successful elimination of severe vaso-occlusive events.

October 20, 2023 — Lovo-cel therapy consists of autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector (LVV) encoding the human beta-A-T87Q globin gene. It has been evaluated in the phase 1/2 HGB-205 (NCT02151526) and HGB-206 (NCT02140554) clinical trials, the former evaluating the therapy for both SCD and beta-thalassemia and the latter only involving participants with SCD. It is currently being evaluated in the phase 3 HGB-210 clinical trial (NCT04293185) for treating SCD.

“I think it'll be a little bit complicated as we wander into this new territory of high-priced therapies... but I think the patients that I have taken care of would tell you it is absolutely worth it. It is truly a transformative therapy."

– Julie Kanter, MD, of UAB

5. FDA Approves Bristol Myers Squibb's Reblozyl for Expanded Indication in Myelodysplastic Syndromes

• Luspatercept-aamt (Reblozyl) by Bristol Myers Squibb gets FDA nod for first-line anemia treatment in lower-risk myelodysplastic syndromes.
• COMMANDS study showed twice as many patients achieved transfusion independence with luspatercept-aamt compared to epoetin alfa.
• Luspatercept-aamt's safety profile aligns with expectations, marking a crucial advancement for lower-risk MDS patients.

August 28, 2023 — The FDA has approved Bristol Myers Squibb’s first-in-class erythroid maturation agent luspatercept-aamt (Reblozyl) as a first-line treatment for anemia in adult patients with very low, low-, or intermediate-risk (IPSS-R) myelodysplastic syndromes (MDS) who may require red blood cell (RBC) transfusions. The decision was based on data from the randomized, open-label phase 3 COMMANDS clinical trial (NCT03682536.

"Results from the COMMANDS study showed nearly twice as many patients treated with Reblozyl achieved transfusion independence of at least 12 weeks and concurrent hemoglobin increase compared to epoetin alfa. Today’s approval represents an important advancement for patients with lower-risk MDS.”

– Andrew Guillermo Garcia-Manero, MD, of MD Anderson