FDA Fast Tracks Graphite Bio's Sickle Cell Disease Gene-Edited Cell Therapy

The FDA has granted fast track designation to Graphite Bio's GPH101, its investigational gene-edited autologous hematopoietic stem cell therapy for the treatment of sickle cell disease.¹

The regulatory designation comes as Graphite continues enrollment in its phase 1/2 clinical trial (NCT04819841) of GPH101, which was previously granted orphan drug designation by the agency.

The therapy, which utilizes a CRISPR-Cas9 gene correction approach to correct the mutation in the beta-globin gene, would effectively decrease production of sickle hemoglobin and restore adult hemoglobin expression.

"This designation has the potential to accelerate the development of GPH101, which we are advancing with the goal of precisely and efficiently correcting the genetic mutation that is the underlying cause of sickle cell disease," said Josh Lehrer, MD, MPhil, chief executive officer of Graphite Bio, in a statement.¹ "We continue to enroll patients in our Phase 1/2 CEDAR trial and expect to dose our first patient later this year, with initial proof-of-concept data anticipated next year."

The open-label, multicenter phase 1/2 CEDAR trial will assess the safety, engraftment success, gene correction rates, and total hemoglobin, among other end point, in a target population of 15 participants age 12 to 40 years old with severe sickle cell disease.

“While allogeneic transplant is the only available cure for sickle cell disease, the procedure has several limitations, mainly lack of available donors and risk of graft versus host disease. Other available therapies are considered palliative as they do not specifically reverse end-organ damage. This type of gene therapy – reducing sickle hemoglobin production at the same time as restoring adult hemoglobin expression through direct gene correction – would be an ideal curative option in sickle cell disease,” said Julie Kanter, MD, associate professor of medicine and co-director of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham, and CEDAR investigator, in a prior statement.² “As an investigator in the CEDAR trial, I look forward to assessing GPH101’s potential to be a curative option for patients.”

Graphite's platform utilizes a "find and replace" approach that uses a cell's own homology directed repair mechanism to correct a defect or insert a new gene. Their pipeline includes 2 programs which are in investigational new drug-enabling studies, GPH201 for X-linked severe combined immunodeficiency syndrome and GPH301 for Gaucher disease type 1. In addition, Graphite has preclinical programs in beta-thalssemia and alpha-1 antitrypsin deficiency, and a discovery program focused on developing a nongenotoxic stem cell-targeted conditioning regimen.

REFERENCES

1. Graphite Bio Announces U.S. FDA Fast Track Designation Granted to GPH101 for the Treatment of Sickle Cell Disease. News release. Graphite Bio. May 3, 2022. https://ir.graphitebio.com/press-releases/detail/70/graphite-bio-announces-u-s-fda-fast-track-designation
2. Graphite Bio Presents Overview of Phase 1/2 CEDAR Trial Evaluating Investigational Gene Editing Therapy GPH101 in Sickle Cell Disease at 63rd ASH Annual Meeting and Exposition. News release. Graphite Bio. December 11, 2021. https://ir.graphitebio.com/press-releases/detail/62/graphite-bio-presents-overview-of-phase-12-cedar-trial