Long-term Follow-up of Subjects with Sickle Cell Disease Treated with Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced with a Lentiviral Vector

This is a multi-center, long-term safety and efficacy follow-up study for subjects with sickle cell disease who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored clinical studies. After completing the parent clinical study (approximately 2 years), eligible subjects will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in the study.

Start Date21 Oct 2020

Sponsor / Collaborator

bluebird bio, Inc.

NCT04293185

/ Active, not recruitingPhase 3

A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With the BB305 Lentiviral Vector in Subjects With Sickle Cell Disease

This is a non-randomized, open-label, multi-site, single-dose, Phase 3 study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD). The study will evaluate hematopoietic stem cell (HSC) transplantation (HSCT) using bb1111 (also known as LentiGlobin BB305 Drug Product for SCD).

Start Date14 Feb 2020

Sponsor / Collaborator

bluebird bio, Inc.

NCT02140554

/ CompletedPhase 1/2

A Phase 1/2 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With the LentiGlobin BB305 Lentiviral Vector in Subjects With Severe Sickle Cell Disease

This is a non-randomized, open label, multi-site, single dose, Phase 1/2 study in approximately 50 adults and adolescents with severe SCD. The study will evaluate hematopoietic stem cell and progenitor stem cell (collectively referred to as hematopoietic stem and progenitor cells or HSPCs) transplantation using lovo-cel.

Start Date02 Feb 2015

Sponsor / Collaborator

bluebird bio, Inc.

100 Clinical Results associated with Lovotibeglogene autotemcel

100 Translational Medicine associated with Lovotibeglogene autotemcel

100 Patents (Medical) associated with Lovotibeglogene autotemcel

Literatures (Medical) associated with Lovotibeglogene autotemcel

01 May 2025·PharmacoEconomics

Innovative Payment Models for Sickle-Cell Disease Gene Therapies in Medicaid: Leveraging Real-World Data and Insights from CMMI’s Gene Therapy Access Model

Article

Author: McQueen, R Brett ; DiStefano, Michael J ; Nair, Kavita ; Wright, Garth C ; Leonard, Jim ; Zemplenyi, Antal ; Anderson, Kelly E

OBJECTIVEThis study aims to evaluate the financial implications of implementing various payment models, including outcome-based agreements (OBAs), volume-based rebates, and guaranteed rebates, for the newly approved gene therapies, exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel), in the treatment of sickle-cell disease (SCD) from the perspective of Colorado Medicaid. The analysis specifically examines the cost of standard of care (SoC) for severe SCD, the impact of different eligibility criteria based on vaso-occlusive events (VOEs), and the potential financial impacts associated with rebate structures.METHODSData from the Colorado Department of Health Care Policy & Financing (HCPF) database was used to estimate the annual costs for Medicaid-enrolled patients with severe SCD from 2018 to 2023. Patients were selected based on various eligibility criteria, including the number of VOEs, acute chest syndrome events, and stroke diagnoses. Three-state Markov models (SCD, stable, and dead) were constructed to compare the costs of SoC and gene therapies. The durability of gene therapy effectiveness and the financial impact of OBAs, volume-based rebates, and guaranteed rebates were evaluated over a 6-year contract period, with scenarios reflecting different VOE criteria and treatment durability.RESULTSThe average annual SoC cost for severe SCD patients (N = 138) was US$45,941 (SD US$59,653), with higher costs associated with more frequent VOEs. Gene therapies exa-cel and lovo-cel, with one-off list prices of US$2.2 million and US$3.1 million, respectively, exhibited high upfront costs, resulting in a negative cumulative balance averaging - US$2.11 million for exa-cel and - US$3.00 million for lovo-cel per patient over 6 years compared with SoC. Outcome-based rebates could potentially save Medicaid approximately US$260K (uncertainty interval 88K-772K) per patient on average for exa-cel and US$367K (uncertainty interval 122K-1111K) for lovo-cel after they pay the full up-front cost. Volume-based and guaranteed rebates also offered potential savings but varied in impact based on contract duration and effectiveness of gene therapy.CONCLUSIONSThe study highlights critical considerations for Medicaid in negotiating OBAs for SCD gene therapies. Achieving budget neutrality over 6 years is unlikely due to low SoC costs. However, payment models can enhance value-based spending by linking high therapy costs and potential rebates to the health gains these treatments may offer. OBAs offer offsets contingent on therapy effectiveness durability and contract terms (such as length and price), while varying eligibility criteria impact budgets and outcomes. Medicaid real-world data is crucial for navigating complexities in defining eligible populations and structuring OBAs.

01 May 2025·Advances in Therapy

Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials

Review

Author: Locatelli, Franco ; Xuan, Fengjuan ; Imren, Suzan ; Li, Nanxin ; Eckrich, Michael J ; Frangoul, Haydar ; Grupp, Stephan A

INTRODUCTIONPatients with sickle cell disease (SCD) experience recurrent, severe pain events due to vaso-occlusion. Eliminating these acute pain events is a key outcome in SCD clinical trials; however, the definition of a vaso-occlusive crisis (VOC) or a vaso-occlusive event (VOE) has not been consistently applied, hampering comparisons of treatment efficacy between different therapeutic approaches. We have examined the degree to which differing definitions of vaso-occlusion in clinical trial endpoints impact efficacy outcomes.METHODSDescriptions of clinical endpoints related to vaso-occlusion and pain events were reviewed from trials of exagamglogene autotemcel (exa-cel), lovotibeglogene autotemcel (lovo-cel), renizgamglogene autogedtemcel (reni-cel), hydroxyurea, L-glutamine, voxelotor, and crizanlizumab. Patient-level data from the published exa-cel Phase 3 pivotal trial (CLIMB SCD-121; data cut 14 Jun 2023) was used to evaluate efficacy outcomes based on differing endpoint definitions of vaso-occlusion.RESULTSIn the seven clinical trials reviewed, definitions of vaso-occlusion and/or pain events varied by care setting, duration of care, treatments used, and associated complications, with the frequency and duration of medical facility visits for acute pain events being most dissimilar between trials. Definitions of severe VOCs (exa-cel), VOC (voxelotor), and sickle cell-related pain crises (SCPCs; crizanlizumab and L-glutamine) included pain events requiring a medical facility visit of any duration, whereas the definition of painful crises (hydroxyurea) required a medical facility visit of > 4 h and the definition of severe vaso-occlusive events (VOEs; lovo-cel and reni-cel) required a hospital or emergency room (ER) observation unit visit lasting ≥ 24 h or ≥ 2 visits to a day unit or ER over a 72-h period. Based on the definition of severe VOCs, 29/30 patients [96.7%; 95% confidence interval (CI): 82.8, 99.9] in the CLIMB SCD-121 trial were considered free from severe VOCs for ≥ 12 consecutive months, whereas when the severe VOEs definition was applied to the same data, all patients (30/30; 100.0%; 95% CI: 88.4, 100.0) were considered free from severe VOEs for ≥ 12 consecutive months.CONCLUSIONDifferences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials.

01 Jan 2025·Cytotherapy

Sickle cell disease gene therapy drug expenses and reimbursement: a litmus test for commercial pricing strategy and patient access for curative therapies

Article

Author: Galipeau, Jacques ; Hume, Ashley ; Grilley, Bambi J

Durable gene therapies newly approved by the Food and Drug Administration for sickle cell disease offer the promise of cure with subsequent improvement in quality of life through avoidance of repeated hospitalizations and worsening of disabilities in these patients. In the United States, following Food and Drug Administration approval, lovotibeglogene autotemcel (Lyfgenia, bluebird bio, Inc, Sommerville, MA, USA) and exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals Inc, Boston, MA, USA) were launched in 2024 for treatment of patients 12 years and older with frequent vaso-occlusive crises. Here we will discuss the first treatment with lovotibeglogene as a test case serving to highlight the multiple drug reimbursement pathways in the United States for cell and gene products for orphan disorders and their impact on patient adoption and access.

137

News (Medical) associated with Lovotibeglogene autotemcel

17 Apr 2025

·www.pharmaceutical-technology.com

Bluebird bio reaffirms Carlyle deal as Ayrmid misses deadline

bluebird has been under financial pressure for several years. Credit: SOPA Images via Getty Images. Bluebird bio (bluebird) has reaffirmed its support for a proposed acquisition by Carlyle and SK Capital after rival bidder Ayrmid failed to deliver a binding offer or secure financing by the extended deadline. The announcement marks the second time Ayrmid has initiated discussions with bluebird without producing a fully financed proposal. Bluebird said it had engaged with Ayrmid for three weeks following the private equity firm’s unsolicited bid in March, including extending the original deadline to allow more time for due diligence and deal structuring. However, Ayrmid did not submit a definitive proposal by the agreed-upon 15 April cut-off date and has yet to secure the necessary capital to proceed. As a result, bluebird’s board of directors is reiterating its unanimous support for the acquisition agreement with Carlyle and SK Capital, which was first announced in February 2025. The board is urging shareholders to tender their shares by the updated deadline of 2 May, extending the previous expiration date of 18 April. bluebird’s board chairman Mark Vachon said: “Ayrmid’s proposal remains highly conditional. bluebird has engaged with Ayrmid on two separate occasions—neither of which has resulted in a binding or fully-financed offer. The board unanimously reaffirms its support of the previously announced agreement with Carlyle and SK Capital in the strongest possible terms.” Bluebird has been under significant financial pressure for several years. The company currently faces the risk of defaulting on a $175m loan from Hercules Capital, secured in 2024 to support ongoing operations. Without a new capital injection, the board said, the company’s liquidity position remains precarious. Carlyle and SK Capital’s proposal offers $3 per share in cash, along with a potential additional payment of $6.84 per share if certain clinical and commercial milestones are met. Ayrmid‘s offer, disclosed last month, proposed $4.50 per share upfront and the same milestone-based payout structure. However, bluebird confirmed that Ayrmid has not demonstrated access to committed funding. bluebird noted that Ayrmid is continuing to seek financing and may provide further updates in the coming days. bluebird’s financial position has deteriorated over time, despite achieving several key regulatory milestones. The company currently markets three US Food and Drug Administration (FDA)- approved gene therapies – Zynteglo (betibeglogene autotemcel) for transfusion-dependent beta-thalassemia, Skysona (elivaldogene autotemcel) for cerebral adrenoleukodystrophy, and Lyfgenia (lovotibeglogene autotemcel) for sickle cell disease – but has struggled with slow uptake, high costs, and reimbursement hurdles. In 2023, the company suffered a major setback when the FDA denied a priority review voucher (PRV) for Lyfgenia. Bluebird had already arranged to sell the voucher to Novartis for $103m, but the agency ruled that the therapy’s active ingredient had previously been used in Zynteglo, for which the company had already received a PRV in 2022. The loss of the expected funds deepened bluebird’s financial strain. To fill the gap, bluebird pursued emergency financing through a $150m public stock offering underwritten by Goldman Sachs and JP Morgan, as well as up to $100m in receivables financing from Alterna Capital Solutions. The company has also undergone repeated cost-cutting efforts, including workforce reductions of 30% in 2022 and an additional 25% last year. Despite these efforts, bluebird’s therapies continue to face stiff competition. Lyfgenia is priced at $3.1m per patient, while a competing treatment, Casgevy (exagamglogene autotemcel) from Vertex Pharmaceuticals and CRISPR Therapeutics, is listed at $2.2m. Both therapies were approved on the same day in December 2023 to treat sickle cell disease. Going public in 2013, bluebird has seen its stock decline sharply in recent years. Following the 16 April update, shares closed down by 7%. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic You have a right to withdraw your consent at any time, by clicking here . We may still continue to send you service-related and other non-promotional communications. For more information relating to our privacy practices, we invite you to review our privacy policy .

AcquisitionPriority ReviewDrug ApprovalCell TherapyGene Therapy

07 Jan 2025

·endpts.com

Vertex signs in vivo gene editing delivery pact for sickle cell and thalassemia as it looks beyond Casgevy

Vertex Pharmaceuticals signed a three-year deal with Orna Therapeutics to use the RNA biotech’s delivery particles to develop its next iteration of gene editing treatments for sickle cell disease and beta thalassemia. The partnership announcement comes just over a year after Vertex received the first approval for a gene-edited therapy for sickle cell disease and thalassemia known as Casgevy. Unlike Casgevy, where cells are edited outside the body and then reinfused back to the patient, Vertex’s goal here is to use Orna’s lipid nanoparticles (LNPs) — which are essentially spherical fatty acid shuttles — to deliver gene editors directly to the blood stem cells in a patient’s body. Vertex paid Orna $65 million, including an undisclosed amount in a convertible note. All in all, Orna could receive up to $635 million in milestones for the sickle cell and thalassemia programs. It could receive another $365 million related to up to 10 additional programs in other indications if Vertex opts in. Orna’s also eligible for tiered royalties on a potential product from this deal. “This [Orna’s LNP] technology, and the encouraging results the team has generated to date, offer a promising starting point for the discovery of LNPs to enable in vivo delivery of Vertex’s gene editing therapies,” a Vertex spokesperson told Endpoints News in an email. While the program is likely several years from human studies, the hope is that an in vivo gene editing therapy could be more straightforward to manufacture and could make obsolete the need for the grueling chemotherapy conditioning that is currently required to receive Casgevy as well as Lyfgenia and Zynteglo, which are sickle cell and beta thalassemia gene therapies marketed by bluebird bio. Both of those factors could also make such a therapy more accessible, where only a small fraction of sickle cell patients will be able to receive the currently approved gene therapies. Vertex is funding the three-year research partnership and has the option to extend it. The Vertex spokesperson wrote that the company has an internal research program for in vivo gene editing therapies and it is “pursuing multiple targets and approaches” for in vivo gene editing for sickle cell and beta thalassemia. The spokesperson did not say when the company expects to be entering human studies, saying that they would provide more details once they got closer to seeking regulatory clearance for clinical trials. One of the key bottlenecks in the gene editing field has been delivering gene editors outside of the liver. Lipid nanoparticles have been effective at delivering to the liver, but not beyond it. Researchers have been seeking new ways to deliver gene editors, including by attaching various targeting molecules to LNPs. However, Orna’s extrahepatic LNP doesn’t use added attachments. “These are all passive. These are not targeted. You don’t conjugate anything to the LNP,” Orna chief scientific officer Joe Bolen said. “It’s pretty flabbergasting, if you ask me, that we get really excellent non-hepatic delivery to various places.” Vertex said that Orna’s initial data demonstrated the passive delivery of LNPs to blood stem cells. But Bolen said the mechanism behind how Orna’s LNPs target beyond the liver hasn’t been determined and the company’s still investigating the details. In May, Orna and ReNAgade Therapeutics announced they were merging under the name Orna after both companies conducted layoffs amid a downturn in the genetic medicine industry. Following the merger, the company laid off more employees. Orna’s focus was developing therapies around circular RNA, while ReNAgade sought to develop RNA-based therapies with new lipid nanoparticles. The Vertex deal centers around the technology from ReNAgade — the startup generated a large barcoded library of LNPs that it infused “lot by lot,” in the words of Bolen, into non-human primates to study them. Others, including Tessera and Editas , are also pursuing in vivo gene editing for sickle cell disease. And in the near term, companies such as Vertex and its partner CRISPR Therapeutics, as well as Beam Therapeutics, are working to develop treatments that employ safer conditioning and could spare patients from harsh side effects of chemotherapy conditioning that include sores and infertility. Vertex is also researching small molecule approaches for sickle cell, according to its website.

Gene TherapyAcquisitionLicense out/in

18 Dec 2024

·www.biopharmadive.com

Tessera gets sickle cell funding; Corvus shares slide on eczema data

Today, a brief rundown of news involving Tessera Therapeutics and Corvus Pharmaceuticals, as well as updates from Sarepta Therapeutics, Cara Therapeutics and Johnson & Johnson that you may have missed.The Bill & Melinda Gates Foundation will invest as much as $50 million to support Tessera Therapeutics development of a curative genetic treatment for sickle cell disease that can work without the intensive preparatory regimens needed for drugs like Casgevy and Lyfgenia. Tessera, which specializes in technology it says can change single DNA letters as well as add whole genes, is developing its sickle cell therapy as an in vivo treatment, meaning it does its modification to cell genes directly inside the body. Casgevy and Lyfgenia are ex vivo, built from editing patient cells in a laboratory. Simpler in vivo therapies could be an important to bringing genetic medicine to parts of the world without advanced healthcare infrastructure. Ned PagliaruloShares in Corvus Pharmaceuticals collapsed Wednesday, shedding nearly half of their value following the companys release of study data for its drug soquelitinib in people with eczema. Results came from the first portion of a Phase 1 study involving 12 participants given Corvus drug and four who received placebo. The data showed roughly similar skin clearance in both groups through 15 days, but greater clearance for soquelinitib-treated volunteers than those on placbeo through 28 days. Ned PagliaruloSarepta Therapeutics on Wednesday said it has finished enrolling a Phase 3 study of a gene therapy its developing for a type of limb-girdle muscular dystrophy. The company expects data from the trial in the first half of next year and, if positive, anticipates that theyd support an approval application to the Food and Drug Administration. Sarepta is also developing gene therapies for other forms of the muscle-weakening disease. Ned PagliaruloCara Therapeutics and private biotechnology firm Tvardi Therapeutics have agreed to merge, giving Tvardi an entry to public markets to help fund development of medicines for fibrotic diseases. Once the deal closes, the new company will operate under Tvardis name and a new ticker, TVRD. Its combined cash on hand will fund operations into the second half of 2026, before which Tvardi expects data from two Phase 2 studies of its experimental STAT3 blocker in idiopathic pulmonary fibrosis and hepatocellular carcinoma. Separately, Cara has reached a deal with Vifor Fresenius Medical Care Renal Pharma to sell rights to its approved drug Korsuva. Delilah AlvaradoThe Food and Drug Administration has rejected Johnson & Johnsons application for a subcutaneous form of its lung cancer drug Rybrevant. The complete response letter cited findings from a pre-approval inspection of a manufacturing facility and did not flag concerns with the drug product, or its safety and efficacy, J&J said. The company plans to work closely with the agency to bring the under-the-skin shot to market. The approved intravenous formulation of Rybrevant is not affected by the complete response letter. Delilah Alvarado '

Clinical ResultPhase 3Phase 1Phase 2Gene Therapy

100 Deals associated with Lovotibeglogene autotemcel

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Anemia, Sickle Cell	United States	bluebird bio, Inc.	08 Dec 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Chest Syndrome	Phase 2	United States	bluebird bio, Inc.	02 Feb 2015
Anemia, Sickle Cell	Preclinical	France	bluebird bio, Inc.	07 Jun 2013
Beta-Thalassemia	Preclinical	France	bluebird bio, Inc.	07 Jun 2013
Transfusion-dependent Beta Thalassemia	Preclinical	France	bluebird bio, Inc.	07 Jun 2013

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02140554 (HGB-210, Tandem Meetings ASTCT and CIBMTR2024) Manual	Phase 1/2	Anemia, Sickle Cell	47	Lovotibeglogene Autotemcel (Lovo-cel) (Lovo-cel)	(jtanngxcqp) = wpzxmtxhtn toyqwqnjmh (lklcaqijfc ) View more	Positive	01 Feb 2024
NCT02151526 (CTgov)	Phase 1/2	Beta-Thalassemia \| Transfusion-dependent Beta Thalassemia \| Anemia, Sickle Cell	7	LentiGlobin BB305 (LentiGlobin BB305 Drug Product for SCD)	qiptxpjhuh(qotpaodort) = qzocxeznmo ikpcvyuebq (svvruayqzr, wkybasykhv - xmdjhztcnz) View more	-	10 Mar 2020
NCT02151526 (CTgov)	Phase 1/2		7	LentiGlobin BB305 (LentiGlobin BB305 Drug Product for TDT)	qiptxpjhuh(qotpaodort) = pthqxhiaav ikpcvyuebq (svvruayqzr, amutnvwjuw - hwwgwikzzx) View more	-	10 Mar 2020

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