An ex vivo gene-edited cell therapy for sickle cell disease (SCD) being developed by Sangamo Therapeutics and Sanofi has generated positive early Phase I/II results in three patients—data that persuaded a committee of the European Medicines Agency (EMA) to support an orphan designation for the drug candidate.

The EMA’s Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion for the orphan designation for BIVV003 (autologous CD34+ hematopoietic stem and progenitor cells transfected with zinc finger nuclease mRNAs SB-mRENH1 and SB-mRENH2) following its meeting of January 19-21—minutes of which were posted this month on the EMA’s website.

COMP based its recommendation on data showing that the first three patients with sickle cell disease ended up “without recurrence of previous SCD symptoms” following treatment with BIVV003 in the Phase I/II PRECIZN-1 trial (NCT03653247).

“Increases in expression of HbF [fetal hemoglobin] have also been reported in accordance with the assumed mechanism of action,” the committee added.

The three patients had 52 weeks, 13 weeks, and 29 days of follow-up, respectively, following treatment with BIVV003.

“OH. MY. GREGOR. (and Rosalind),” exclaimed Fyodor Urnov, PhD, director for technology and translation at the Innovative Genomics Institute at the University of California (UC), Berkeley, who was not connected with the study, in a tweet on Friday that referred to genetics pioneers Gregor Mendel and Rosalind Franklin.

Investors signaled their enthusiasm for Sangamo’s news by sending its shares up 11.55% on Friday, to $13.23 from $11.86, a closing price unchanged from Wednesday.

“Seems promising”

“Though relatively early follow-up, the benefit observed seems promising,” Maury Raycroft, PhD, equity analyst at Jefferies, and two colleagues observed Friday in a research note.

Sangamo and Sanofi are not the only developers to report positive clinical data for new treatments against SCD in recent months. In January, CRISPR Therapeutics and Vertex Pharmaceuticals reported positive results for their CRISPR-Cas9 gene-edited therapy candidate CTX001 in a patient with SCD and a patient with transfusion-dependent β-thalassemia (TDT), according to data from a pair of Phase I/II trials that was published in The New England Journal of Medicine.

Another developer of an SCD treatment, Bluebird Bio, temporarily and voluntarily suspending two clinical trials assessing its LentiGlobin gene therapy for sickle cell disease (SCD; bb1111), following reports that two participants in the earlier-phase study developed blood cancers—one of acute myeloid leukemia (AML), the other of myelodysplastic syndrome (MDS).

Earlier this month, however, Bluebird said its BB305 lentiviral vector (LVV) was “very unlikely” to have played a role in the patient with AML. The company continues to investigate the MDS case.

BIVV003 is an autologous cell therapy that incorporates gene editing of a patient’s own hematopoietic stem cells using Sangamo’s zinc finger nuclease (ZFN) technology. The genomic modification occurs within an endogenous BCL11A enhancer sequence.

According to the COMP committee, the first patient was of HbSS (homozygous genotype) and on hydroxyurea 500 mg daily for several years, and had frequent hospitalizations due to 10 severe vaso-occlusive crises (VOCs) including hospitalizations within the past two years before being enrolled in the study.

The second treated patient also had a HbSS genotype and a complex medical history of numerous VOCs, and had received chronic red blood cell exchanges since she was seven years old. The third treated patient also had a previous history of chronic red blood cell transfusions and a VOC in the two years prior to enrollment, COMP reported.

“Significant benefit”

“Although satisfactory methods of treatment of the condition exist in the European Union, the sponsor has provided sufficient justification for the assumption that the medicinal product containing autologous CD34+ hematopoietic stem and progenitor cells transfected with zinc finger nuclease mRNAs SB-mRENH1 and SB-mRENH2 will be of significant benefit to those affected by the condition,” the COMP concluded, according to the minutes of its meeting.

“The sponsor has provided preliminary clinical observations supporting a reduction in vaso-occlusive crises, as well as long term effects that may obviate the need of frequent treatment,” COMP added. “The Committee considered that this constitutes a clinically relevant advantage.”

The three treated patients were among six recruited for the PRECIZN-1 trial, an open label, multicenter study, for which Sangamo and Sanofi expect to recruit a total of eight adults with severe sickle cell disease. The study is designed to assess the safety, tolerability, and efficacy of autologous hematopoietic stem cell transplantation using BIVV003. The study’s estimated primary completion date is November 2023.

In a separate statement Wednesday, Sangamo and Sanofi said they expect to submit updated data from the PRECIZN-1 study for presentation at a medical meeting later this year. At that time, the companies said, they will also provide an update on another Sanofi-partnered clinical trial assessing another ex vivo gene-edited cell therapy candidate being developed by the two companies for a blood disorder, ST-400 in beta thalassemia.

Sangamo and Sanofi are partnering in an exclusive worldwide collaboration to develop and commercialize zinc finger nuclease-mediated gene-edited cell therapies for the treatment of beta thalassemia and sickle cell disease.

The partnership was launched in 2014 by Sangamo and Biogen. When Biogen spun out its global hemophilia business in 2017, the spinout company Bioverativ took over Biogen’s portion of the collaboration before being acquired by Sanofi a year later for $11.6 billion. Sanofi continues Bioverativ’s obligation to conduct the BIVV003 Phase I/II clinical trial and subsequent worldwide clinical development, manufacturing, and commercialization of products.