Cell therapy for sickle cell disease abandoned as Graphite Bio lays off 50% of workforce

By Jonathan Smith

- Last updated on GMT

© Getty Images
© Getty Images

Related tags cell and gene therapies sickle cell disease CRISPR blood disorder

After voluntarily pausing a phase 1/2 trial due to safety concerns in January 2023, the gene edited cell therapy firm Graphite Bio has discontinued the development of nulabeglogene autogedtemcel (nula-cel), its lead candidate cell therapy for sickle cell disease, and has halved its workforce.

The cost-cutting move came as Graphite reviewed the status of its business and decided that it would take too much resources to continue with nula-cel. Instead, the company plans to explore external partners for development of nula-cel and will focus on other programs in its pipeline.

Sickle cell disease is an inherited blood disorder that causes red blood cells to take an abnormal shape and reduces their ability to deliver oxygen around the body. This causes vaso-occlusive crises for sufferers, which cause pain, inflammation and potentially even organ damage. The only cure for the condition is a bone marrow transplant, but these can risk a serious complication called graft versus host disease where the transplanted blood cells attack the body.

Gene editing in sickle cell disease

Gene editing therapies are already in development as potential cures for sickle cell disease. The most advanced is Vertex Therapeutics’ and CRISPR Therapeutics’ ex vivo therapy exa-cel​, which is undergoing the market approval decision process with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. However, traditional approaches to gene editing are best at knocking out genes, and struggle to insert new genes efficiently. 

Launched in 2020, Graphite Bio is developing a different kind of gene editing technology based on a process called homology directed repair. The technology is designed to insert new genes and minimize off-target edits better than older technology. Nula-cel in particular corrects the mutation responsible for sickle cell disease to reverse its effects.

Nonetheless, Graphite Bio’s clinical trial aspirations hit a bump last month when nula-cel caused a serious adverse event in the first patient enrolled in the first-in-human phase 1/2 trial CEDAR. The patient had unexpected prolonged low blood cell counts that needed ongoing transfusion and growth factor treatments. While the event didn’t meet the requirements to halt the study, Graphite paused the trial as a precautionary measure.

“We believe that gene correction is the optimal way to treat sickle cell and many other genetic diseases. However, after an extensive assessment of the nula-cel program, we made the difficult decision to discontinue nula-cel development based on the time and resources needed to resume the CEDAR study and the evolving treatment landscape for sickle cell disease,” said Josh Lehrer, chief executive officer of Graphite Bio. 

“We remain deeply grateful to the patients, investigators and study staff for their participation in CEDAR, to the sickle cell community for their partnership and to our entire Graphite Bio team for their commitment and dedication to our company.”

Next in the pipeline

At the start of 2023, Graphite Bio had around $283.5 million in cash, cash equivalents and investments in marketable securities; the latest changes are intended to conserve its cash reserves until at least 2026. As it drops nula-cel, Graphite will proceed with a preclinical-stage program researching ways to condition patients for receiving bone marrow transplants that are less harsh than radiation and cyotoxic drugs used in current approaches.

In addition, Graphite Bio is developing a therapy for the genetic blood disorder beta thalassemia called GPH102. The therapy is designed to correct a mutated gene encoding a key part of the oxygen transporting protein hemoglobin, which causes the disease. The firm didn’t mention this candidate in its latest release, but previously indicated that it would be delayed in entering clinical testing by the setback with the CEDAR trial. 

Related topics Cell & Gene Therapies

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