Gene Therapy for Sickle Cell Disease: Competitive Landscape, Clinical Development Programs and Market Forecast


- Sickle cell disease is an inherited blood disorder of hemoglobin synthesis 
- Affects 100,000 individuals in the United States
- Financial forecast show approximately 1 billion dollar market with CGAR of 14.3%
- Potential curative gene therapy are being Bluebird Bio, Aruvant Therapeutics, CRISPR Therapeutics, Editas Therapeutics, Intellia Therapeutics, Sangamo Biosciences, Homology Medicine
- Bluebird Bio has a competitive advantage 

Phases of Clinical Development Program

Sickle Cell Disease
Sickle cell disease is an inherited blood disorder characterized by the production of an altered form of hemoglobin which polymerizes and becomes fibrous, causing red blood cells to become rigid and change form so that they appear sickle shaped instead of soft and rounded. Patients with sickle cell disease suffer from debilitating episodes of sickle cell crises, which occur when the rigid, adhesive, and inflexible red blood cells occlude blood vessels.

Sickle cell crises cause excruciating pain as a result of insufficient oxygen being delivered to tissue, referred to as tissue ischemia, and inflammation. These events may lead to organ damage, stroke, pulmonary complications, skin ulceration, infection, and a variety of other adverse outcomes. Sickle cell disease is a significant unmet medical need, affecting approximately one hundred thousand patients in the U.S. and millions worldwide, the majority of which are of African descent.

Sickle cell disease affects 100,000 individuals in the United States, disproportionately affecting African Americans with one in 500 African Americans suffering from the disease. Currently, 20 to 25 million people worldwide are living with inherited sickle cell traits and about 300,000 infants are born with the disease every year. 

Global Market Financial Forecast
The global sickle cell disease treatment market size was valued at USD 2.1 billion in 2017 and is anticipated to exhibit a compound annual growth rate (CAGR) of 14.3% during the forecast period (Grandviewresearch). 

Bluebird Bio, Aruvant Therapeutics, CRISPR Therapeutics, Editas Therapeutics, Intellia Therapeutics, Sangamo Biosciences, Homology Medicine are the biotechnology companies that are developing a potentially curative treatment.

Lentiviral Gene Therapy 

Bluebird Bio (bb111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. LentiGlobin for SCD was designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis, and other complications.

bluebird bio’s clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study

The result from Phase 1/2 HGB-206 study of investigational LentiGlobin™ gene therapy (bb1111) for adult and adolescent patients with sickle cell disease (SCD) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up. (Read More)

Aruvant Therapeutics (ARU-1801)
ARU-1801 is a one-time potentially curative investigational gene therapy for individuals living with sickle cell disease. ARU-1801 incorporates a patented modified gamma-globin into autologous stem cells, with the aim of restoring normal red blood cell function through increased levels of fetal hemoglobin. The high potency of the modified gamma-globin enables ARU-1801 engraftment with only reduced-intensity conditioning (RIC). 

Aruvant’s clinical development program for modified gamma-globin lentivirus for SCD includes open label Phase 1/2 clinical study (MOMENTUM)

ARU-1801 demonstrated clinically meaningful long-term reductions in sickle cell disease burden. 

CRISPR Based Treatment 

CRISPR Therapeutics Partnered with Vertex

CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and reduce painful and debilitating sickle crises for SCD patients.

Vertex/CRISPR's clinical development program for CTX-001 for SCD includes an open-label Phase 1/2 clinical study (CLIMB-SCD-121). 

Of two patients dosed, one patient is free of vaso-occlusive crises at 9 months after CTX001 infusion (Read more) 

Editas Therapeutics
EDIT-301 is an experimental, autologous cell therapy medicine under investigation for the treatment of sickle cell disease. EDIT-301 is comprised of sickle patient CD34+ cells genetically modified using a highly specific and efficient CRISPR/Cas12a (also known as Cpf1) ribonucleoprotein (RNP) to edit the HBG1/2 promoter region in the beta-globin locus. Red blood cells derived from EDIT-301 CD34+ cells demonstrate a sustained increase in fetal hemoglobin (HbF) production, which has the potential to provide a durable treatment benefit for people living with sickle cell disease.

Editas submitted an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for the initiation of a Phase 1/2 clinical trial of EDIT-301 (Read More).  

Intellia Therapeutics Partnered with Novartis
OTQ923/HIX763 is an investigational SCD treatment based on genome editing of hematopoietic stem cells (HSCs), using CRISPR/Cas9 RNA guides identified through Intellia’s cell therapy research collaboration with Novartis. This therapeutic approach results in highly targeted editing of the HSC’s DNA to induce fetal hemoglobin (HbF) expression. The edited cells are returned to the patient, where the expression of HbF is expected to reduce the deleterious effects of sickle hemoglobin (HbS).

Intellia/Novarts's clinical development program OTQ923/HIX763 for SCD includes an open-label Phase 1/2 clinical study (CLIMB-SCD-121). 

Interllia reported that OTQ923/HIX763 had achieved approximately 80-95 percent target site modification in human hematopoietic stem and progenitor CD34+ cells following electroporation of ribonucleoprotein (RNP) composed of Cas9 and a guide RNA (gRNA), selected for efficacy and potency. In addition, it has also demonstrated an approximately 40 percent reduction in BCL11A mRNA with a corresponding two-fold increase in γ-globin transcript and 30-40 percent more fetal hemoglobin-positive cells above background (ASH2020).

ZFN Based Treatment 

Sangamo Therapeutics Partnered with Sanofi

BIVV003 is an investigational ex vivo gene-edited cell therapy for the treatment of people with sickle cell disease being developed in collaboration with Sangamo Therapeutics, Inc. BIVV003 is a non-viral cell therapy that involves gene editing of a patient’s own hematopoietic stem cells (HSCs) using zinc finger nuclease (ZFN) technology to address underlying disease pathophysiology. 

A Phase 1/2 clinical trial to assess the safety, tolerability, and efficacy of BIVV003 in adults with sickle cell disease has been initiated. 

Homology Medicine 
Discovery phase

Aruvant Therapeutics
CRISPR Therapeutics
Editas Therapeutics
Bluebird Bio
Sangamo Therapeutics

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