Prime editing therapy shows early neutrophil activity in two patients with p47-deficient CGD

This Phase 1 clinical trial evaluated PM359, an autologous CD34+ hematopoietic stem-cell therapy using prime editing to correct the delGT variant, in two participants with p47-deficient chronic granulomatous disease (p47-CGD). The intervention was administered after myeloid conditioning with busulfan. The study did not report a comparator group, primary outcome, or specific sample size details beyond the two participants.

Main results from the early follow-up period showed that neutrophil and platelet engraftment occurred promptly in both patients. NADPH oxidase activity in neutrophils was observed within 1 month and was maintained, with the last follow-up visits at 6 months for Participant 1 and 4 months for Participant 2. The study did not report specific effect sizes, absolute numbers, or statistical measures for these outcomes.

Regarding safety, adverse events were reported as being consistent with myeloid conditioning with busulfan. The study did not report details on serious adverse events, discontinuations, or tolerability. The trial was funded by Prime Medicine. A key limitation is the extremely small sample size of only two participants and the very short follow-up duration of 1.0 months for the reported data, with longer individual follow-ups noted. The certainty of evidence is low, as explicitly noted, because this is a Phase 1 trial with two participants.

The practice relevance is appropriately restrained: the authors conclude these results support further investigation of prime editing of CD34+ cells to treat p47-CGD. No causal claims are made. This represents preliminary proof-of-concept data requiring validation in larger, controlled trials with longer follow-up to establish efficacy and safety.