Editas' Latecomer SCD Therapy Shows Promise in Two Patients

Baisong Mei and Gilmore O'Neill_Editas

Baisong Mei and Gilmore O'Neill, Editas CMO and CEO/Company Courtesy 

Editas Medicine released positive proof of concept data Tuesday from the first patients dosed with its experimental CRISPR-based gene therapy for sickle cell disease.

The patients were administered EDIT-301, a gene therapy that uses AsCas12a. This is said to be a highly efficient and specific nuclease capable of editing the promoter regions of gamma-globin genes 1 and 2. The Phase I RUBY trial marks the first time AsCas12a was used to edit human cells in a clinical trial.

Although only two patients have been dosed in the trial, Gilmore O’Neill, who took over the role of CEO earlier this year, said the data looks promising.

In a conference call Tuesday morning, O'Neill said the first patient treated with EDIT-301 showed improvements in hemoglobin levels.

Additionally, the patient posted a mean corpuscular fetal hemoglobin (HbF) level of 13.8 pg/red blood cell. That exceeds the 10 pg/red blood cell threshold to suppress red blood cell sickling.

The first patient was dosed five months ago, and the second patient was infused with EDIT-301 less than two months ago. O’Neill noted that both patients have also not required transfusions since being infused with EDIT-301. The therapy is designed to disrupt the binding site of BCL11a and ameliorate disease symptoms.

O’Neill said this approach increases the expression of HbF that mimics the natural mechanism of hereditary persistence of fetal hemoglobin to treat sickle cell disease. 

Editas said both of the patients who have been treated showed successful neutrophil and platelet engraftment.

Baisong Mei, who also joined Editas earlier this year as the CMO, stressed in the conference call that neither patient has experienced any vaso-occlusive events since treatment with EDIT-301. Prior to treatment, both patients typically experienced multiple vaso-occlusive events annually.

Editas anticipates data from more trial participants by mid-2023. At this time, O’Neill said the team is not prepared to share specific numbers for the number of patients the company will be enrolling and dosing in 2023. He did say Editas is actively adding new additional sites for the study and are expecting an increase in patient participation.

The Treatment Landscape

There are already multiple treatments available for sickle cell disease patients, including Pfizer’s Oxbryta (voxelotor) and Novartis’ Adakveo (crizanlizumab-tmca), among others.

Beyond Oxbryta, Pfizer is also developing inclacumab and GBT021601 for sickle cell disease. Both investigational assets received orphan drug and rare pediatric disease designations earlier this year.

Companies like Graphite Bio, bluebird bio, Vertex and CRISPR Therapeutics are developing gene therapy approaches to treating SCD.

Like Editas, Graphite is in the early stages of clinical development for its gene therapy treatment. And bluebird plans to file a Biologics License Application for lovo-cel, a LentiGlobin gene therapy, which has been administered to more than 50 patients in clinical studies. It is currently under a partial clinical hold for patients under the age of 18.

In September, Vertex and CRISPR announced plans to submit a BLA for exagamglogene autotemcel (exa-cel), their gene therapy for both sickle cell and beta-thalassemia. An autologous, ex vivo CRISPR/Cas9 gene-edited therapy, exa-cel edits a patient’s own hematopoietic stem cells to produce high levels of fetal hemoglobin.

While Editas may not be the first gene therapy to win approval for sickle cell disease, O’Neill said his team's ASCas12a approach will differentiate itself and ultimately be more effective than other therapies on the market. 

Mei added he has received positive feedback from the sickle cell disease community regarding Editas’ approach. He said advocacy groups are interested in their science and are “showing enthusiasm” for gene therapies that have the potential to alleviate current treatment options.  

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