Two patients with sickle cell disease involved with a gene-based therapy trial now have been diagnosed with cancer, and the clinical trial that is their hope for a cure has been halted. Apparently, after being treated 5.5 years ago by bluebird bio, a patient developed myelodysplastic syndrome, a type of cancer that can lead to leukemia. And according to recent reports, yet another patient developed acute myeloid leukemia. But are these two conditions related to the bluebird bio experimental gene therapy? With such a setback however, many patients with sickle cell hoping for a cure will have to continue waiting. In the meantime, the stock plummeted from 45.76 on Feb 12 to 26.07 as of today.
TrialSite breaks down this most recent news.
What happened? What studies were halted?
The company placed its Phase 1/2 (HGB-206) and Phase 3 (HGB-210) studies of LentiGlobin gene therapy for sickle cell disease (SCD) (bb1111) on a temporary suspension due to a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML).
What are the company’s gene-based therapies?
What is HGB-206 and HGB-210?
First, the company develops a gene-based therapy treatment known as HGB-206, ongoing in Phase 1/2 open-label clinical trial designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A, B and C. A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.
While HGB-210 is an ongoing Phase 3 single-arm open-label study set up to evaluate the efficacy and safety of LentiGlobin gene therapy for SCD in patients between two years and 50 years of age with sickle cell disease.
What is LentiGlobin for SCD (bb1111)?
L LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study.
Now the U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD. Moreover, the investigational gene therapy received orphan medical product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September, 2020.
bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: here or clinicaltrials.gov and use identifier NCT04628585 for LTF-307. LentiGlobin for SCD is investigational and has not been approved in any geography.
Why were they put on hold?
Well, in line with the clinical study protocols for HGB-206 and HGB-210, bluebird bio placed the studies on temporary suspension following a report received last week that a patient who was treated more than five years ago in Group A of HGB-206 was diagnosed with AML. The company is investigating the cause of this patient’s AML in order to determine if there is any relationship to the use of BB305 lentiviral vector in the manufacture of LentiGlobin gene therapy for SCD. In addition, a second SUSAR of myelodysplastic syndrome (MDS) in a patient from Group C of HGB-206 was reported last week to the company and is currently being investigated.
Has any hematologic malignancies surfaced in patients who has received treatment with betibeglogene autotemcel for transfusion-dependent β-thalassemia (licensed as ZYNTEGLOTM in the European Union and the United Kingdom)?
No. However, because it is also manufactured using the same BB305 lentiviral vector used in LentiGlobin gene therapy for SCD, the company has decided to temporarily suspend marketing of ZYNTEGLO while the AML case is assessed.
Is an independent review board monitoring the company’s studies as well as regulators involved?
Yes. The independent safety review board monitoring the company’s studies as well as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have been advised of these cases, and bluebird bio will continue to work with regulatory agencies to complete its investigation.
Is bluebird committed to patient safety?
Absolutely. The company’s CEO Nick Leschly reported that the “safety of every patient who has participated in our studies or is treated with our gene therapies is the utmost priority for us.”
Does this news impact the company’s valuation? Check out a recent presentation on the topic. The company’s share price experienced a precipitous decline in just days from 45.76 on Feb 12 to 26.07 as of today.
Note the company was subject in a TrialSite story called “A Familyman’s battle against the forefront of capitalist medicine: the case of Errant Gene Therapeutics,” where a competitor accused bluebird of more than just sharp dealing.