California-based Kamau Therapeutics has released preliminary results from the first cohort of its gene-editing study in sickle cell disease (SCD). The data cover three patients treated with nula-cel, an experimental therapy designed to directly correct the disease-causing mutation in the β-globin gene. Further results are due to be presented at next month’s American Society of Hematology (ASH) meeting.
All three patients became independent of transfusions before leaving hospital and have had no reported pain crises since receiving their edited stem cells. In the two patients with at least six months of follow-up, adult hemoglobin (HbA) was predominant and sickle hemoglobin (HbS) accounted for less than 20% of total hemoglobin. Their total hemoglobin levels were above 10 g/dL.
Kamau’s approach uses homology-directed repair to replace the faulty HbS gene with a functional HbA copy. This differs from the fetal-hemoglobin strategy used by Casgevy, which aims to counter the effects of SCD by increasing production of fetal hemoglobin rather than correcting the mutation directly.
The company said bone marrow measurements showed corrected gene variants at about 20%, consistent with continued engraftment of edited stem cells. Single-cell analyses also found that more than 90% of circulating red blood cells contained protective levels of HbA. Kamau reported no serious adverse events attributed to nula-cel or its revised gene-editing process, though some events were consistent with the conditioning treatment and stem-cell transplant.
The findings come from the Phase I/II RESTORE trial, which is enrolling around 15 participants. The upcoming ASH presentation will include results from the three patients treated using Kamau’s revised manufacturing process, as well as further follow-up of an earlier patient first treated four years ago in a study run by Graphite Bio, Kamau co-founder Matthew Porteus’s former company.
Porteus said the early results support continued enrollment and discussions with the U.S. Food and Drug Administration about the design of a registration trial. Nula-cel has received Fast Track and Orphan Drug designations from the FDA. The therapy is made by editing a patient’s own stem cells outside the body before reinfusing them.