Lentiviral Cell Therapy Normalizes Hemoglobin in Pyruvate Kinase Deficiency


RP-L301 also improved hemolysis and eliminated the need for red blood cell transfusions for up to 1year after therapy.

RP-L301, a gene-edited lentiviral mediated hematopoietic stem and progenitor cell (HSPC) therapy, seems to be efficacious and safe in patients with pyruvate kinase deficiency (PKD).

Rocket Pharmaceuticals’ therapy, which is being assessed in an ongoing phase 1 study (NCT04105166), restored normal levels of hemoglobin production, improved hemolysis and sustained transgene expression with no need for red blood cell transfusions at 1-year post infusion.

These data were presented at the 2022 American Society of Gene and Cell Therapy Annual Meeting, May 16-19, 2022, in Washington DC, by Ami J. Shah, MD, clinical professor of pediatrics, Division of Hematology/ Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford Medicine.

“We expected some gradual improvement and we expected maybe they feel a little bit better. But we didn't really expect people to come out of this completely normal... [in terms of] side effects, they don't even feel like they had a transplant and... they can't remember this disease anymore,” Shah told CGTLive in an interview.

The study has treated 2 adult, splenectomizedpatients with severe, transfusion-dependent anemia PKD as of January 2022. Investigators collected mobilized peripheral blood (PB) HSPCs via apheresis, then enriched and transduced them with PGK-coRPK-WPRE lentiviral vector before cryopreservation. Participants received myeloablative busulfan over 4 days before receiving the gene-edited cell therapy product and were then followed for up to 1 year after treatment. Investigators assessed PB and bone marrow (BM) genetic correction, transfusion need, anemia, reduction of hemolysis, and patient-reported-outcomes (PROs).

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The participants were 31 and 47 years at enrollment. Patient 1 received a dose of 3.9x106 CD34+ cells/kg with mean vector copy number (VCN) of 2.73 and patient 2 received a dose of 2.4x106 CD34+ cells/kg with mean VCN of 2.08. Both patients have sustained transgene expression, normalized hemoglobin, improved hemolysis and no red blood cell transfusion requirements as of 1-year post infusion. PROs have also shown significant improvements, with increases in scores on both the Functional Assessment of Cancer Therapy-Anemia and 36-Item Short Form Survey instruments. Marked improvements were seen specifically in energy/fatigue, physical functioning, and general health domains.

“Since the transplantation and steadily afterwards, from 3months and then on, [patients] have continued to show marked improvements in energy levels, in work ability, in quality of health, in susceptibility to infections - especially considering we did this trial during the middle of a pandemic. Both adults were really healthy throughout the whole entire thing. They were around people that got sick, and they didn't get sick. It's been amazing to see just how they're living their lives,” Shah told CGTLive.

Shah AJ, López Lorenzo JL, Navarro S, et al. Changing the treatment paradigm for pyruvate kinase deficiency with lentiviral mediated gene therapy: Interim results from an ongoing global phase 1 study. Presented at: ASGCT 25th Annual Meeting, May 16-19, 2022. Abstract #357
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