Long-Term Follow-Up Data Continue to Support Beti-Cel as a Potentially Curative Gene Therapy for β-Thalassemia Patients Who Require Regular Transfusions Through Achievement of Durable Transfusion Independence and Normal or Near-Normal Adult Hb Levels
bluebird bio (NASDAQ: BLUE) presented updated data for betibeglogene autotemcel (beti-cel/ZYNTEGLO™) in beta-thalassemia patients at the 66th ASH Annual Meeting. The long-term follow-up data, extending beyond 10 years in the earliest treated patients, demonstrates sustained treatment effects with 90.2% of Phase 3 and 68.2% of Phase 1/2 study participants achieving transfusion independence (TI).
Key findings include median weighted average hemoglobin of 10.2 mg/dL for Phase 1/2 and 11.2 mg/dL for Phase 3 studies. Among participants achieving TI, 75.7% no longer require iron chelation therapy. The safety profile remained consistent with known side effects, with no reports of malignancies or serious adverse events related to beti-cel after 2 years post-infusion.
bluebird bio (NASDAQ: BLUE) ha presentato dati aggiornati per betibeglogene autotemcel (beti-cel/ZYNTEGLO™) in pazienti con beta-talassemia durante il 66° Congresso Annuale dell'ASH. I dati di follow-up a lungo termine, che si estendono oltre i 10 anni nei pazienti trattati per primi, dimostrano effetti terapeutici sostenuti, con il 90,2% dei partecipanti agli studi di Fase 3 e il 68,2% di quelli di Fase 1/2 che hanno raggiunto l'indipendenza dalle trasfusioni (TI).
I risultati chiave includono una media ponderata della emoglobina di 10,2 mg/dL per gli studi di Fase 1/2 e di 11,2 mg/dL per gli studi di Fase 3. Tra i partecipanti che hanno raggiunto la TI, il 75,7% non richiede più terapia chelante per il ferro. Il profilo di sicurezza è rimasto costante con gli effetti collaterali noti, senza segnalazioni di malignità o eventi avversi gravi correlati a beti-cel dopo 2 anni dalla infusione.
bluebird bio (NASDAQ: BLUE) presentó datos actualizados sobre betibeglogene autotemcel (beti-cel/ZYNTEGLO™) en pacientes con beta-talasemia durante la 66ª Reunión Anual de la ASH. Los datos de seguimiento a largo plazo, que se extienden más de 10 años en los pacientes tratados inicialmente, demuestran efectos de tratamiento sostenidos, con el 90,2% de los participantes de los estudios de Fase 3 y el 68,2% de los estudios de Fase 1/2 alcanzando independencia de transfusiones (TI).
Los hallazgos clave incluyen una hemoglobina media ponderada de 10,2 mg/dL para los estudios de Fase 1/2 y de 11,2 mg/dL para los estudios de Fase 3. Entre los participantes que alcanzaron TI, el 75,7% ya no requiere terapia de quelación de hierro. El perfil de seguridad se mantuvo consistente con los efectos secundarios conocidos, sin informes de malignidades ni eventos adversos graves relacionados con beti-cel después de 2 años post-infusión.
bluebird bio (NASDAQ: BLUE)는 66회 ASH 연례 회의에서 베타-탈라세미아 환자에 대한 베티베글로겐 아우토템셀(베티-셀/ZYNTEGLO™)의 업데이트된 데이터를 발표했습니다. 가장 초기 치료 환자에서 10년 이상 연장된 장기 추적 데이터는 3상 연구 참가자의 90.2%와 1/2상 연구 참가자의 68.2%가 수혈 독립성(TI)을 달성함을 보여줍니다.
주요 발견사항으로는 1/2상 연구의 평균 가중 헤모글로빈이 10.2 mg/dL, 3상 연구의 경우 11.2 mg/dL임이 포함됩니다. TI에 도달한 참가자 중 75.7%는 더 이상 철 주사 요법을 필요로 하지 않습니다. 안전성 프로필은 알려진 부작용과 일관되며, 베티-셀과 관련된 악성 종양이나 심각한 부작용 보고는 2년 후 수혈 후 없었습니다.
bluebird bio (NASDAQ: BLUE) a présenté des données mises à jour concernant le betibeglogene autotemcel (beti-cel/ZYNTEGLO™) chez des patients atteints de bêta-thalassémie lors de la 66e réunion annuelle de l'ASH. Les données de suivi à long terme, s'étendant sur plus de 10 ans chez les premiers patients traités, démontrent des effets de traitement soutenus, avec 90,2% des participants de l'étude de Phase 3 et 68,2% des participants de l'étude de Phase 1/2 atteignant l'indépendance transfusionnelle (TI).
Les principales conclusions incluent un hémoglobine moyenne pondérée de 10,2 mg/dL pour les études de Phase 1/2 et de 11,2 mg/dL pour les études de Phase 3. Parmi les participants atteignant la TI, 75,7% n'ont plus besoin de traitement de chélation de fer. Le profil de sécurité est resté cohérent avec les effets secondaires connus, sans rapports de malignités ou d'événements indésirables graves liés au beti-cel après 2 ans post-infusion.
bluebird bio (NASDAQ: BLUE) hat aktualisierte Daten zu betibeglogene autotemcel (beti-cel/ZYNTEGLO™) bei Patienten mit Beta-Thalassämie auf dem 66. ASH-Jahrestreffen präsentiert. Die langfristigen Follow-up-Daten, die sich über mehr als 10 Jahre bei den zuerst behandelten Patienten erstrecken, zeigen nachhaltige Behandlungseffekte, wobei 90,2% der Teilnehmer der Phase-3-Studie und 68,2% der Phase-1/2-Studie die Transfusionunabhängigkeit (TI) erreicht haben.
Zu den wichtigen Ergebnissen gehören ein medianes gewogenes durchschnittliches Hämoglobin von 10,2 mg/dL für Phase-1/2-Studien und 11,2 mg/dL für Phase-3-Studien. Unter den Teilnehmern, die TI erreicht haben, benötigen 75,7% keine Eisenchelationstherapie mehr. Das Sicherheitsprofil blieb konsistent mit den bekannten Nebenwirkungen, ohne Berichte über Malignitäten oder schwerwiegende unerwünschte Ereignisse im Zusammenhang mit beti-cel nach 2 Jahren nach der Infusion.
- 90.2% of Phase 3 study participants achieved transfusion independence
- 75.7% of Phase 3 participants who achieved TI no longer need iron chelation therapy
- Treatment effects sustained for over 10 years in earliest treated patients
- No serious adverse events reported after 2 years post-infusion
- Favorable safety profile with no malignancies or insertional oncogenesis reported
- Lower success rate in Phase 1/2 studies with 68.2% achieving transfusion independence
Insights
Treatment effects sustained through long-term follow-up of beyond 10 years in the earliest treated patients (n=2);
“Updated follow-up data of up to 10 years showed that patients treated with beti-cel in clinical trials experienced durable transfusion independence and normal or near-normal hemoglobin, regardless of genotype and age, and a continued favorable safety profile”, said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “We are deeply grateful for the ongoing commitment of our investigators, patients, and study participants. Our collective efforts are not only advancing the field of gene therapy but also providing new hope and possibilities for individuals with severe genetic diseases."
“Data at ASH demonstrate the durability of beti-cel through 10 years of long-term follow-up, giving additional confidence in that the transformational outcomes observed in parent studies are sustained over time,” said Alexis Thompson, MD, MPH, Chief of the Division of Hematology at Children’s Hospital of
Betibeglogene Autotemcel (beti-cel) Gene Addition Therapy results in durable Hemoglobin A (HbA) Production with up to 10 Years of Follow-Up in Participants with Transfusion-Dependent β-Thalassemia (Poster #2194)
Long-term outcomes with beti-cel in adult and pediatric patients with TDT were presented in a poster session. The data focused on 63 adult and pediatric study participants who had received beti-cel in a Phase 1/2 or Phase 3 study. Two participants had 10 years of follow-up, and 51 (
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Of 63 patients, 52 (
90.2% in Phase 3 studies and68.2% in Phase 1/2 studies) achieved TI. All except one patient maintained TI through last follow-up. The median weighted average hemoglobin during TI was 10.2 mg/dL for Phase 1/2 studies and 11.2 mg/dL for Phase 3 studies. Achievement and maintenance of TI and median weighted average hemoglobin were similar across ages and genotypes.
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Study participants treated with beti-cel who achieved and maintained TI demonstrated effective restoration of iron homeostasis over time and reduced iron management burden. Among participants who achieved TI, improvements in serum ferritin and liver iron concentration were sustained through month 60. 28/37 (
75.7% ) study participants who achieved TI in Phase 3 studies are no longer undergoing iron chelation therapy.
- Both adult and pediatric health-related quality of life scores (HRQoL) remained above the normative population mean up to 60 months. All 26 participants who achieved TI and completed a questionnaire reported an overall benefit with beti-cel.
- The safety profile was consistent with known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. None of the study participants had a fatal event. No beti-cel–related serious adverse events were reported more than 2 years after infusion through last follow-up. No malignancies, insertional oncogenesis or vector-derived replication-competent lentivirus were reported in any study participants.
Beti-cel was approved by the FDA in August 2022 and is commercially available in
About ZYNTEGLO® (betibeglogene autotemcel) or beti-cel
ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy approved for the treatment of beta-thalassemia in adult and pediatric patients who require regular red blood cell transfusions. ZYNTEGLO works by adding functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem and progenitor cells to enable the production of a modified functional adult hemoglobin (HbAT87Q). Once a patient has the βA-T87Q-globin gene, they have the potential to increase ZYNTEGLO-derived adult hemoglobin (HbAT87Q) and total hemoglobin to normal or near normal levels that can eliminate the need for regular red blood cell (RBC) transfusions.
Indication
ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions.
Important Safety Information
Delayed Platelet Engraftment
Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia;
Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise.
Risk of Neutrophil Engraftment Failure
There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells.
Risk of Insertional Oncogenesis
There is a potential risk of LVV mediated insertional oncogenesis after treatment with ZYNTEGLO.
Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted.
In the event that a malignancy occurs, contact bluebird bio at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis.
Anti-retroviral and Hydroxyurea Use
Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.
Interference with Serology Testing
Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR‑based assay.
Adverse Reactions
The most common non-laboratory adverse reactions (≥
Drug Interactions
Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates.
Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.
Pregnancy/Lactation
Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility. ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician.
ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician.
Females and Males of Reproductive Potential
A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration.
Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO.
Advise patients of the option to cryopreserve semen or ova before treatment if appropriate.
Please see full Prescribing Information for ZYNTEGLO.
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days.
Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers.
With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward.
bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding the therapeutic potential of ZYNTEGLO. Such forward-looking statements are based on historical performance and current expectations and projections about bluebird’s future goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond bluebird’s control and could cause bluebird’s future goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC. These risks and uncertainties include, but are not limited to: the risk that the efficacy and safety results from bluebird’s prior and ongoing clinical trials will not continue or be seen in the commercial context; the risk that there is not sufficient patient demand or payer reimbursement to support continued commercialization of ZYNTEGLO; the risk of insertional oncogenic or other safety events associated with lentiviral vector, drug product, or myeloablation, including the risk of hematologic malignancy; and the risk that bluebird’s products, including ZYNTEGLO, will not be successfully commercialized. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, bluebird bio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
View source version on businesswire.com: https://www.businesswire.com/news/home/20241207259439/en/
Investors:
Courtney O’Leary, 978-621-7347
coleary@bluebirdbio.com
Media:
Jess Rowlands, 857-299-6103
jess.rowlands@bluebirdbio.com
Source: bluebird bio, Inc.
FAQ
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