Disease: Sickle Cell Disease, SCD, (GPH101)

Disease info:

Sickle cell disease is a group of disorders that affects haemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical haemoglobin molecules called haemoglobin S, which can distort red blood cells into a sickle or crescent shape.

The production of haemoglobin A, which is the principle type of haemoglobin in humans, is governed by 3 genes: HBA1, HBA2, and HBB. Each haemoglobin A molecule consists of two alpha and two beta chains, and mutations in either of the HBA or the HBB genes may result in abnormal haemoglobin molecules with reduced or diminshed function. Sickle cell diseaase arises from a single point mutation in the 6th codon of the beta-globin gene (HBB), which results in a valine instead of a glutamic acid in the haemoglobin beta-chain.

Abnormal haemoglobin ultimately leads to anaemia as well as other symptoms, depending on the exact mutations present. Diseases caused by defective haemoglobin fall into a larger category of diseases known as the "haemoglobinopathies" which also include the thalassemias, a related group of diseases that are characterised by reduced or deficient rather than abnormal haemoglobin. 

Frequency:
Sickle cell disease is the most common inherited blood disorder in the United States, affecting 70,000 to 80,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.
Official title:
GPH101
Who:
Sponsor:

Graphite Bio

Partners:

Stanford University Center for Definitive and Curative Medicine

Locations:
Study start:
Enrollment:
Gene editing method:
CRISPR-Cas
Type of edit:
Gene disruption and gene correction
Gene:
Haemoglobin Subunit Beta (HBB)
Delivery method:
Unknown - Ex-vivo
Indicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status:

Description

The CEDAR clinical trial is expected to begin early in 2021. This will test the very first experimental treatment designed to correct the mutation that is the underlying cause of sickle cell disease. With targeted gene integration, GPH101 seeks to restore normal haemoglobin expression.

CEDAR is a Phase 1/2, multi-center, open-label clinical study designed to evaluate the safety, preliminary efficacy and pharmacodynamics of GPH101 in adult and adolescent patients with severe SCD.

GPH101 investigational therapy harnesses the power of CRISPR and DNA’s natural homology-directed repair mechanisms to cut out the mutation in the sickle globin gene and paste in the correct natural (wild-type) DNA sequence, with the aim of curing SCD through directly correcting the underlying disease-causing mutation and leading to the production of completely normal red blood cells.

Last updated: Jan. 13, 2021
Source: US National Institutes of Health (NIH)
clinicaltrials.gov
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