Bluebird bio’s sickle cell gene therapy shows early-study benefit

Closely follows approval of beta thalassaemia therapy Zynteglo

Bluebird bio’s gene therapy for sickle cell disease (SCD), LentiGlobin, has demonstrated significant benefit in a small group of patients treated in a phase 1/2 study. 

Hot-on-the-heels of Bluebird’s approval for its groundbreaking beta thalassaemia gene therapy Zynteglo (autologous CD34+ cells encoding βA-T87Q-globin gene), the biotech has revealed new data for its SCD gene therapy LentiGlobin.

LentiGlobin is designed to add functional copies of a modified form of the β-globin gene, which does not work as it should in SCD sufferers, into a patient’s own hematopoietic stem cells. When patients have copies of the functional gene, their red blood cells can produce anti-sickling haemoglobin which decreases the amount of the faulty sickled haemoglobin.

The results from the ongoing phase 1/2 HGB-206 study were presented at ASH 2019, and included additional patients treated and updated data from the pivotal trial.

The updated data includes findings from 17 patients treated with LentiGlobin over 21 months – the results were promising, with none of those who previously suffered from pain attacks experiencing any while receiving the therapy. Over 40% of haemoglobin present in the treated patients red blood cells were found to be the healthier form (anti-sickling haemoglobin) thanks to the effects of the gene therapy.

Out of the 17 treated, nine patients with at least six or more months of follow-up who had experienced at least four vaso-occlusive crises (VOC) or acute chest syndrome (ACS) events in the two years prior to treatment with LentiGlobin, experienced a 99% reduction in the annualised rate of these events.

There was also no reports of either VOC or ACS events up to 21 months post-infusion.

“The data continues to demonstrate sustained expression of gene therapy-derived haemoglobin in patients treated with LentiGlobin for SCD, which resulted in significantly improved haemoglobin (>2g/dl/patient), near-normalisation of markers of hemolysis and no reports of acute chest syndrome, stroke or serious vaso-occlusive crises in these patients,” said Julie Kanter, University of Alabama at Birmingham.

The LentiGlobin data is impressive, but Bluebird is not alone in the sickle cell market, with a number of other therapies for the disease also emerging.

This includes Global Blood Therapeutics’ Oxbryta (voxelotor), which recently won FDA approval for the treatment of SCD in patients aged 12 and over.

The FDA also cleared Novartis’ anti-P-selectin antibody Adakveo (crizanlizumab) to reduce VOCs – one of the most serious complications of SCD.

Bluebird’s own Zynteglo is also in late-stage development for SCD, which could help it to secure a more dominant space in the market.

On the gene therapy front, Bluebird may face competition from Vertex and CRISPR Therapeutics, who recently penned a deal for the development of up to six gene therapies, including candidates for SCD and other haemoglobinopathies.

The partners recently revealed initial positive data from the first two patients treated with the investigational CRISPR/Cas9 gene-editing therapy CTX001. The two patients both had severe haemoglobinopathies, including severe SCD and transfusion-dependant beta thalassaemia.