Graphite's hopes for sickle cell 'cure' blunted after first patient dosed experiences serious event

A year and a half after exceeding expectations with its $238 million IPO, Graphite Bio has hit a major roadblock as an adverse event caused the gene-therapy-focused biotech to pause its lead program.

The company cited a “serious adverse event in the first patient dosed” with its gene therapy nulabeglogene autogedtemcel (nula-cel) as part of a phase 1/2 trial for sickle cell disease. The event is likely to be related to the treatment, the company concluded in a press release.

Specifically, a patient experienced prolonged low blood cell counts, requiring ongoing transfusion and growth factor support. Graphite reported the incident to the FDA and in the meantime has voluntarily paused the trial.

While Graphite said the event didn’t meet the requirements to halt the study, both the clinical investigators and the trial’s safety monitoring committee agreed with the decision to suspend the dosing of additional patients while the company tries to find out what happened. 

“We are committed to working closely with our scientific and clinical experts to fully assess this event and identify a potential path to resume the CEDAR study,” CEO Josh Lehrer, M.D., said in a postmarket release Thursday. “We are grateful for the partnership with the sickle cell community, our clinical investigators, our founders and scientific experts and the FDA as we determine next steps for our nula-cel program in sickle cell disease.”

The patient was first dosed back in August. Nula-cel, the company’s only candidate to reach the clinic so far, is a gene editing therapy designed to directly correct the genetic mutation that causes sickle cell disease and "definitively cure the condition."

The adverse event derails both Graphite’s clinical and financial strategies. Plans for beta thalassemia treatment GPH102 to enter the clinic by mid-2024 no longer seem likely, admitted the company, which is now working to “identify operational efficiencies to extend its cash position to at least 2026.”

Regular readers of Fierce Biotech’s layoff tracker will know that phrase is often associated with either workforce layoffs or major pipeline alterations. It remains to be seen what approach Graphite will take.

Investors certainly seem rattled, sending the company's stock plunging 46% in early hours trading to $1.65 a share from a Thursday closing price of $3.06.

It marks a major fall from grace for a company that launched onto the Nasdaq with a $21 share price back in summer 2021 and big ambitions for nula-cel. At the time, Graphite benefited from a trend of preclinical-stage companies going public without any human data—a choice some investors may now be coming to regret.

Graphite isn't the first gene therapy company to have struggled with sickle cell disease, however. Bluebird bio had to wait until last December for the FDA to lift a yearlong clinical hold on its therapy for patients under 18, which was initiated over a case of anemia.