Oral presentation featured within the ASH press program contains long-term knowledge via August 2021 in sufferers who achieved transfusion independence (TI) (n=46) and stay transfusion-free via as much as seven years of follow-up
beti-cel stabilized iron markers in sufferers who achieved TI and had been capable of cease iron chelation (n=20/34), with markers of iron administration enhancing towards regular
Grownup, adolescent and pediatric sufferers skilled early and sustained enchancment in health-related quality-of-life measures from baseline throughout Section 3 research
CAMBRIDGE, Mass.–(BUSINESS WIRE)–$BLUE—bluebird bio, Inc. (Nasdaq: BLUE) right now introduced new outcomes for betibeglogene autotemcel (beti-cel), a deeply studied investigational gene remedy, that exhibit grownup and pediatric sufferers dwelling with β-thalassemia (beta-thal) who require common pink blood cell (RBC) transfusions can produce regular or near-normal ranges of complete hemoglobin and proceed to stay transfusion-free, and obtain steady iron markers, via as much as seven years of follow-up (n=3). These findings additional assist beti-cel as a probably healing one-time therapy choice that addresses the underlying genetic reason behind beta-thal and mitigates the burdens related to the sensible administration of the illness. The info had been highlighted within the press program and can be delivered in an oral presentation on the 63rd American Society of Hematology (ASH) Annual Assembly and Exposition, happening December 11-14, 2021, on the Georgia World Congress Middle in Atlanta and nearly. Information from the pivotal HGB-207 Northstar-2 research had been additionally concurrently revealed in an authentic article in The New England Journal of Medication (NEJM) titled, “Betibeglogene Autotemcel Gene Remedy for Non-β0/β0 Genotype β-Thalassemia.”
“It’s encouraging to see the outcomes introduced at ASH right now exhibiting that beti-cel is probably healing for sufferers with β-thalassemia who require common pink blood cell transfusions, and which construct on the robust proof collected over seven years on this scientific program,” stated Alexis A. Thompson, MD, MPH, Hematology Part Head, Ann & Robert H. Lurie Kids’s Hospital of Chicago. “beti-cel permits the manufacturing of wholesome grownup hemoglobin, which can provide sufferers freedom from lifelong pink blood cell transfusions. Restoring iron homeostasis can also be essential to any particular person’s journey with beta-thal, as iron overload may result from transfusions, in addition to elevated intestinal iron absorption because of ineffective pink blood cell manufacturing. The vast majority of sufferers handled with beti-cel who achieved transfusion independence had been capable of cease iron chelation (or removing), and stabilization of iron markers was sustained even after chelation was discontinued.”
Transfusion-dependent beta-thal is a extreme genetic illness brought on by mutations within the β-globin gene, which can trigger considerably decreased or absent grownup hemoglobin (Hb) manufacturing. This may end up in extreme anemia and lifelong dependence on RBC transfusions, a prolonged course of that sufferers sometimes endure each 3-4 weeks. Regardless of advances in therapy and improved transfusion methods, transfusions solely quickly tackle signs of anemia and folks with beta-thal who require common transfusions have an elevated danger for morbidity and mortality because of treatment- and disease-related iron overload and its issues.
beti-cel is a one-time gene remedy that provides purposeful copies of a modified type of the β-globin gene (βA-T87Q-globin gene) right into a affected person’s personal hematopoietic (blood) stem cells (HSCs). As soon as sufferers have the βA-T87Q-globin gene, the HSCs have the potential to provide gene therapy-derived grownup Hb (HbAT87Q) at ranges that may eradicate the necessity for transfusions. In research of beti-cel, transfusion independence is outlined as now not needing RBC transfusions for not less than 12 months whereas sustaining a weighted common Hb of not less than 9 g/dL.
“These necessary new knowledge construct on a strong physique of scientific proof to bolster the healing potential of beti-cel for sufferers and households dwelling with β-thalassemia, a illness for which therapy advances are urgently wanted,” stated Richard Colvin, MD, PhD, chief medical officer, bluebird bio. “Beti-cel addresses the underlying genetic reason behind beta-thal in sufferers who require common transfusions, enabling the steady manufacturing of grownup hemoglobin and demonstrating sustained enchancment in scientific outcomes via the longest accessible follow-up within the discipline. The sturdy, long-term scientific knowledge within the beti-cel improvement program allow us to watch the really transformative distinction in folks’s lives that transfusion independence offers.”
As of the info cut-off of August 18, 2021, a complete of 63 pediatric, adolescent and grownup sufferers, together with 20 sufferers with not less than 5 years of follow-up, 11 with not less than six years and three with as much as seven years throughout β0/β0 and non-β0/β0 genotypes, have been handled with beti-cel within the Section 1/2 HGB-204 (Northstar) and HGB-205 research and the Section 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) research. Information from bluebird bio’s Section 1/2 and Section 3 scientific research signify greater than 240 patient-years of expertise with beti-cel and the longest accessible follow-up knowledge in beta-thal sufferers requiring common RBC transfusions handled with one-time gene remedy.
“Within the evaluation revealed in NEJM, 91% of sufferers, together with six of seven sufferers beneath the age of 12, achieved transfusion independence in addition to enchancment in erythropoiesis and liver iron concentrations,” stated Professor Franco Locatelli, MD, PhD, lead writer and Director, Division of Pediatric Hematology/Oncology and Cell and Gene Remedy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. “These findings are additional validated with long-term knowledge being introduced at ASH, which counsel that one-time gene remedy with beti-cel is probably healing via achievement of transfusion independence and close to regular hemoglobin ranges.”
Hostile reactions thought-about associated to beti-cel had been few and consisted primarily of non-serious infusion-related reactions that occurred on the day of infusion (e.g., stomach ache, sizzling flush, dyspnea, tachycardia and non-cardiac chest ache) and cytopenias (e.g. thrombocytopenia, leukopenia and neutropenia). Ache in extremity shortly after therapy was additionally documented. One in all these adversarial occasions (AE) was a critical adversarial occasion (SAE) of thrombocytopenia thought-about probably associated to beti-cel and has resolved.
The vast majority of AEs and SAEs within the beti-cel scientific improvement program had been unrelated to beti-cel and according to the recognized negative effects of HSC assortment and busulfan conditioning routine (together with a number of SAEs of veno-occlusive illness that resolved with therapy).
Up to date Lengthy-Time period Efficacy & Security Outcomes (Lengthy-term follow-up research, LTF-303)
After taking part in and finishing the 2 years of follow-up in any of the Section 1/2 (HGB-204, HGB-205) or Section 3 research (HGB-207, HGB-212), sufferers handled with beti-cel had been invited to enroll in a 13-year long-term follow-up research, LTF-303.
As of August 18, 2021, 57 of 63 beti-cel-treated sufferers throughout age teams and genotypes spanning a broad vary of essentially the most extreme β0/β0 and non-β0/β0 genotypes had been enrolled in LTF-303 (22 handled in Section 1/2 research, 35 handled in Section 3 research) with a median post-infusion follow-up of 41.5 months (min-max: 23-87.5). Twenty sufferers enrolled in LTF-303 have not less than 5 years of follow-up.
Transfusion Independence (TI)
Of the 57 sufferers enrolled in LTF-303, 46 sufferers achieved TI: 15/22 (68%) sufferers handled in Section 1/2 and 31/35 (89%) sufferers handled in Section 3. All 46 sufferers who achieved TI maintained it via final follow-up in LTF-303, demonstrating the long-term sturdiness of beti-cel.
Section 1/2 sufferers had a median period of ongoing TI of 65.9 months (min-max: 19.8-84.5) and Section 3 sufferers had a median ongoing TI period of 32 months (min-max: 18.2-49.1).
Weighted common Hb in sufferers who achieved TI reached regular or near-normal ranges within the Section 1/2 research (10.3 g/dL; min-max: 9.1-13.2) and within the Section 3 research (11.6 g/dL; min-max: 9.5-13.7).
Iron Marker Stabilization
Sufferers who require common blood transfusions want to scale back extra iron brought on by persistent blood transfusions. For folks dwelling with beta-thal, iron might be faraway from the physique in a number of methods, together with chelation (pharmacological removing).
Previous to beti-cel infusion, all sufferers had been on iron chelation. Importantly, the vast majority of sufferers who achieved TI (n=46/57) that restarted iron chelation after infusion have since stopped (59%, 20/34); and 24% of those that achieved TI (11/46) had been capable of obtain phlebotomy (blood removing), which is one other technique for iron discount that’s solely potential for sufferers who’ve ample hemoglobin ranges with out RBC transfusions. This helps the potential for beti-cel to scale back the therapy burden related to iron administration.
A sub-analysis of iron standing in LTF-303 included 16 sufferers who achieved TI and stopped chelation, with not less than 9 months of follow-up after discontinuation of chelation. The sub-analysis confirmed iron discount in response to chelation and stabilization of iron markers after chelation was discontinued.
LTF-303 Security
There have been no deaths, no vector-derived replication-competent lentivirus, and no occasions of insertional oncogenesis or malignancy in LTF-303.
No drug-related AEs had been reported. Critical AEs unrelated to beti-cel included infertility points (gonadotropic insufficiency, ectopic being pregnant, fetal dying because of a miscarriage), gallbladder illness (gall bladder wall thickening/polyp), cholelithiasis, an infection and low white blood cell depend within the setting of a wild-type HIV (bacteremia, neutropenia), and particular person occasions of diabetic ketoacidosis, pulmonary embolism, and main despair. Pulmonary embolism occurred concurrently with diabetic ketoacidosis in a affected person with a historical past of thromboembolic occasions. Every occasion was reported as soon as.
Well being-Associated High quality of Life (HRQoL)
“Individuals with β-thalassemia dwell with elevated morbidity and mortality and decreased health-related high quality of life in contrast with the overall inhabitants,” stated Dr. Colvin. “The psychological, bodily, and time calls for of normal, lifelong pink blood cell transfusions, in addition to iron chelation and related issues, take a heavy toll on sufferers’ functioning in all spheres of life, together with their work or college and social lives.i The sturdy, long-term scientific knowledge within the beti-cel improvement program allow us to watch the really transformative distinction in folks’s lives that transfusion independence offers.”
Measures of HRQoL had been evaluated in grownup (≥18 years of age) and pediatric/adolescent (<18 years of age) sufferers who achieved TI following therapy with beti-cel within the Section 3 HGB-207 and HGB-212 research and who accomplished baseline and one post-baseline self-reported HRQoL evaluation. HRQoL was assessed at baseline and at Months 6, 12, 18, and 24 after beti-cel infusion, utilizing a number of validated quality-of-life devices.
Enhancements in HRQoL outcomes had been noticed amongst sufferers throughout age teams and throughout a number of domains of bodily and psychological well being.
Clinically related enhancements had been noticed, as measured by PedsQL and SF-36 scores at Month 24. Sufferers with scores beneath the inhabitants norm at baseline skilled essentially the most enchancment.
Further HQRoL knowledge can be introduced at ASH in a poster titled, Enchancment in Well being-Associated High quality of Life Following Therapy with Betibeglogene Autotemcel in Sufferers with Transfusion-Dependent β-Thalassemia Enrolled in Section 3 Research, on Monday, December 13. Outcomes from the long-term LTF-303 research can be introduced intimately in an oral presentation titled, Restoring Iron Homeostasis in Sufferers who Achieved Transfusion Independence After Therapy with Betibeglogene Autotemcel Gene Remedy: Outcomes from as much as 7 Years of Observe-up, on Monday, December 13 at 11:00 a.m. ET.
About betibeglogene autotemcel (beti-cel)
betibeglogene autotemcel (beti-cel) (pronounced BEH tee cell) is a one-time gene remedy custom-designed to deal with the underlying reason behind β-thalassemia in sufferers who require common pink blood cell (RBC) transfusions. Beti-cel provides purposeful copies of a modified type of the β-globin gene (βA-T87Q-globin gene) right into a affected person’s personal hematopoietic (blood) stem cells (HSCs) so as to appropriate the deficiency of grownup hemoglobin that’s the hallmark of β-thalassemia. As soon as a affected person has the modified β-globin gene, they’ve the potential to provide beti-cel-derived grownup hemoglobin (HbAT87Q) at ranges that will eradicate the necessity for transfusions. In Section 3 beti-cel research 89% (31/35) of evaluable sufferers throughout ages and genotypes, together with pediatric sufferers as younger as 4 years of age and people with essentially the most extreme β0/β0 genotypes, achieved transfusion independence, which is outlined as now not needing RBC transfusions for not less than 12 months whereas sustaining a weighted common Hb of not less than 9 g/dL.
beti-cel is manufactured utilizing the BB305 lentiviral vector (LVV), a third-generation, self-inactivating LVV that has been studied for greater than a decade throughout two therapeutic areas.
Hostile reactions thought-about associated to beti-cel consisted primarily of non-serious infusion-related reactions that occurred on the day of the infusion and cytopenias. One critical adversarial occasion (SAE) of thrombocytopenia thought-about probably associated to beti-cel was reported and has resolved.
The vast majority of AEs and SAEs within the beti-cel scientific improvement program had been thought-about to be unrelated to beti-cel by the Investigator and had been according to recognized negative effects of HSC assortment and the bulsufan conditioning routine.
The Section 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) research evaluating beti-cel are ongoing; enrollment is full, and all sufferers have been handled. bluebird bio can also be conducting a long-term follow-up research, LTF-303, to observe security and efficacy for individuals who have participated in bluebird bio-sponsored beti-cel scientific research via 15 years publish therapy.
A biologics license utility (BLA) for beti-cel is beneath precedence evaluate by the FDA. The company has set a Prescription Drug Consumer Payment Act (PDUFA) aim date of Could 20, 2022.
About bluebird bio, Inc.
bluebird bio is pursuing healing gene therapies to present sufferers and their households extra bluebird days.
With a devoted concentrate on extreme genetic ailments, bluebird has industry-leading scientific and analysis applications for sickle cell illness, β-thalassemia and cerebral adrenoleukodystrophy and is advancing analysis to use new applied sciences to those and different ailments. We {custom} design every of our therapies to deal with the underlying reason behind illness and have developed in-depth and efficient analytical strategies to know the protection of our lentiviral vector applied sciences and drive the sector of gene remedy ahead.
Based in 2010, bluebird has the most important and deepest ex-vivo gene remedy knowledge set on the planet—setting the usual for {industry}. At present, bluebird continues to forge new paths, combining our real-world expertise with a deep dedication to affected person communities and a people-centric tradition that pulls and grows a various flock of devoted birds.
For extra info, go to bluebirdbio.com or observe us on social media at @bluebirdbio, LinkedIn, Instagram and YouTube.
bluebird bio is a trademark of bluebird bio, Inc.
bluebird bio Cautionary Assertion Concerning Ahead-Trying Statements
This press launch incorporates “forward-looking statements” inside the which means of the Personal Securities Litigation Reform Act of 1995. All statements that aren’t statements of historic details are, or could also be deemed to be, forward-looking statements. Such forward-looking statements are based mostly on historic efficiency and present expectations and projections about our future monetary outcomes, objectives, plans and aims and contain inherent dangers, assumptions and uncertainties, together with inner or exterior elements that might delay, divert or change any of them within the subsequent a number of years, which are troublesome to foretell, could also be past our management and will trigger our future monetary outcomes, objectives, plans and aims to vary materially from these expressed in, or implied by, the statements. No forward-looking assertion might be assured. Ahead-looking statements on this press launch ought to be evaluated along with the various dangers and uncertainties that have an effect on bluebird bio’s enterprise, notably these recognized within the danger elements dialogue in bluebird bio’s Annual Report on Kind 10-Ok, as up to date by our subsequent Quarterly Experiences on Kind 10-Q, Present Experiences on Kind 8-Ok and different filings with the Securities and Change Fee. These dangers embody, however should not restricted to: the danger that the efficacy and security outcomes from our prior and ongoing scientific trials won’t proceed or be seen in further sufferers handled with our product candidates; the danger that further insertional oncogenic or different security occasions related to lentiviral vector, drug product, or myeloablation can be found or reported over time; and the danger that anybody or extra of our product candidates won’t be efficiently developed, permitted or commercialized. The forward-looking statements included on this doc are made solely as of the date of this doc and besides as in any other case required by relevant legislation, bluebird bio undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not because of new info, future occasions, modified circumstances or in any other case.
____________________________
i Ladis V, et al. Eur J Haematol. 2011;86(4):332-338.
Jobanputra M, et al. Br J Haematol. 2020;191(5):897-905.
Clarke SA, et al. Youngster Care Well being Dev. 2010;36(1):118-122.
Sobota A, et al. Am J Hematol. 2011;86(1):92-95.
Paramore C, et al. Affected person. 2021;14(2):197-208.
Scalone L, et al. Curr Med Res Opin. 2008;24(7):1905-1917.
Contacts
Traders:
Courtney O’Leary, 978-621-7347
[email protected]
or
Media:
Jess Rowlands, 518-598-3168
[email protected]
