Beti-Cel Induces Transfusion Independence in Patients With β-thalassemia


The findings, which were simultaneously reported in the New England Journal of Medicine, support beti-cel as a potentially curative, one-time treatment option for these patients.

Treatment with betibeglogene autotemcel (beti-cel) produced normal or near-normal levels of total hemoglobin in 3 transfusion-dependent patients with β-thalassemia, who continue to remain transfusion-free and achieve stable iron markers through up to 7years of follow-up, according to long-term data from the LTF-303 trial (NCT02633943) presented at the 2021 ASH Annual Meeting and Exposition.1

As a result, the findings support beti-cel as a potentially curative, one-time treatment option for these patients.

“For these patients–many of whom have been transfusion dependent for decades–being able to discontinue chronic transfusions is an extraordinary, almost unthinkable accomplishment,” said study author Alexis A. Thompson, MD, MPH, of the Ann & Robert H. Lurie Children’s Hospital of Chicago, in a press release issued by ASH. “While there is not yet consensus to say that these patients are cured, we are hopeful that–with 7 years of follow-up to date–we have demonstrated the durability of this gene therapy approach.”

After participating in the phase 1/2 HGB-204 and HGB-205 studies, or the phase 3 HGB-207 and HGB-212 studies, patients treated with beti-cel were invited to enroll in a 13-year long-term follow-up study.

Among 57 patients enrolled, 46 patients are transfusion independent, including 15 patients in the phase 1/2 studies and 31 patients in the phase 3 studies. All patients have maintained independence through follow-up.

Median duration of transfusion independence in the phase 1/2 and phase 3 studies was 65.9 months (range, 19.8-84.5) and 32 months (18.2-49/1), respectively.

The weighted average hemeglobin among those who achieved transfusion independence, reaching normal or near-normal levels, were 10.3 g/dL (range, 9.1-13.2) and 11.6 g/dL (range, 9.5-13.7), respectively, in the phase 1/2 and phase 3 studies.

Prior to infusion, all patients received iron chelation, of which 20 who restarted the regimen after infusion have stopped and 24% of those patients were able to receive phlebotomy.

There were no drug-related adverse events reported.

“It is encouraging to see the results presented at ASH today showing that beti-cel is potentially curative for patients with β-thalassemia who require regular red blood cell transfusions, and which build on the strong evidence collected over seven years in this clinical program,” Thompson said in a release issued by bluebird bio, the agent’s manufacturer. “beti-cel enables the production of healthy adult hemoglobin, which may offer patients freedom from lifelong red blood cell transfusions. Restoring iron homeostasis is also crucial to any person’s journey with beta-thal, as iron overload can result from transfusions, as well as increased intestinal iron absorption due to ineffective red blood cell production. The majority of patients treated with beti-cel who achieved transfusion independence were able to stop iron chelation (or removal), and stabilization of iron markers was sustained even after chelation was discontinued.”

Health-related quality of life (HRQoL) was evaluated in patients who achieved transfusion independence after treatment with beta-cel in the Phase 3 HGB-207 and HGB-212 studies, which was assessed at baseline and at months 6, 12, 18, and 24.

Patients across all age groups demonstrated improvements in HRQoL.

“People with β-thalassemia live with increased morbidity and mortality and reduced health-related quality of life compared with the general population,” said Richard Colvin, MD, PhD, chief medical officer, bluebird bio, in a press release.2 “The mental, physical, and time demands of regular, lifelong red blood cell transfusions, as well as iron chelation and associated complications, take a heavy toll on patients’ functioning in all spheres of life, including their work or school and social lives. The robust, long-term clinical data in the beti-cel development program enable us to observe the truly transformative difference in people’s lives that transfusion independence provides.”

Data from the HGB-207 Northstar-2 study were also simultaneously published in the New England Journal of Medicine.3

In the HGB-207 Northstar-2 study, after a median follow-up of 29.5 months (range, 13.0-48.2), transfusion independence occurred in 20 patients (91%), including 6 patients (86%) under the age of 12.

The average level of hemoglobin during transfusion independence was 11.7 g per deciliter (range, 9.5-12.8). The median level of gene therapy-derived adult hemoglobin with a T87Q amino acid substitution was 8.7 g per deciliter (range, 5.2-10.6) in patients who had transfusion independence at 12 months following beta-cel infusion.

The safety profile of beti-cel was consistent with those previously seen. Four patients had at least 1 AE considered to be related or possibly related to beti-cel; howver, all events were nonserious except for thrombocytopenia that occurred in 1 patient.

“These important new data build on a robust body of clinical evidence to reinforce the curative potential of beti-cel for patients and families living with β-thalassemia, a disease for which treatment advances are urgently needed,” said Colvin. “Beti-cel addresses the underlying genetic cause of beta-thal in patients who require regular transfusions, enabling the stable production of adult hemoglobin and demonstrating sustained improvement in clinical outcomes through the longest available follow-up in the field. The robust, long-term clinical data in the beti-cel development program enable us to observe the truly transformative difference in people’s lives that transfusion independence provides.”

For more coverage of ASH 2021, click here.

1. 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.
2. bluebird bio press release. New Data at ASH21, Published in NEJM Further Demonstrate beti-cel as a Potentially Curative One-Time Gene Therapy for β-thalassemia Patients Who Require Regular Transfusions Through Achievement of Durable TI and Normal or Near-Normal Adult Hb Levels. Published December 11, 2021. Accessed December 12, 2021.
3. Locatelli F, Thompson AA, Kwiatkowski JL, et al. Betibeglogene Autotemcel Gene Therapy for Non–β0/β0 Genotype β-Thalassemia. NEJM. doi:10.1056/NEJMoa2113206.
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