HSC Gene Therapy Demonstrates Improvements in Type 3 Gaucher Disease Case Study


The patient has not re-started any of his previous Gaucher-specific therapy since receiving AVR-RD-02.

AVROBIO’s AVR-RD-02, an investigational hematopoietic stem cell (HSC) gene therapy, has demonstrated sustained improvements in a 12-year-old male patient with type 3 Gaucher disease (GD3).1 The data were presented at the WORLDSymposium 2023, held February 22-26, in Orlando, Florida.

The patient was originally diagnosed with GD3 at 10-months-old and began enzyme replacement therapy (ERT) at 17-months-old. His history of symptoms included a horizontal saccadic eye movement defect at diagnosis; upper motor neuron signs with increased reflexes and tone which progressed during childhood; focal seizures developed at 10 years of age; persistent seizures developed at 11 years of age; worsening mid-thoracic kyphosis; and intellectual function that showed impairment. He also developed massive intraabdominal mesenteric lymphadenitis resulting in a protein-losing enteropathy (PLE) at 4.5-years-old, for which he was treated with diet modification, long-term enteral budesonide, and substrate-reduction therapy (SRT).

Following myeloablative conditioning with busulfan, the patient received AVR-RD-02, which is comprised of autologous CD34+ cells that have been modified ex-vivo to express functional glucocerebrosidase (GCase), the disease-targeted enzyme, in 2 infusions lots. The first lot contained 7.7x108 CD34+ cells/kg and the second lot contained 6.6x106 CD34+ cells/kg. The patient ceased treatment with ERT 1 week prior to the conditioning and ceased treatment with SRT in parallel with the conditioning. The patient achieved engraftment at 10 days after AVR-RD-02 infusion, which was confirmed to have been sustained at 581 days post-infusion via peripheral and bone marrow vector copy number (VCN) data.

Within 6 weeks of AVR-RD-02 infusion, GCase activity increased to the healthy control range (1 to 5 nmol/mg/hr) and has stayed within that range since, reaching 3.5 nmol/mg/hr at the 13-month timepoint. The patient’s levels of chitotriosidase, a biomarker of Gaucher cells, also decreased to the normal range for the first time. Serum albumin, a measure of Gaucher-related lymphatic pathology, reached the highest level (greater than 20 g/L) it had reached in the previous 6 years. The patient has not restarted any of his previous Gaucher-specific therapy since receiving AVR-RD-02. First author Aimee Donald, MBChB, PhD, pediatrician, Royal Manchester Children’s Hospital, and professor, University of Manchester, and colleagues noted that CNS disease symptoms in the patient “appear clinically stable” and that CNS-specific biomarker data were not available at the time of the data cutoff.

In terms of safety, Donald and colleagues wrote that the therapy was tolerated and had “an acceptable adverse event (AE) profile”. They reported that the myeloablative conditioning and infusion procedures were uncomplicated, noting that the patient experienced a single episode of culture negative febrile neutropenia. Treatment for this AE included 48 hours of intravenous antibiotics. Cases of mucositis and alopecia also occurred, and both resolved. The patient remained orally fed throughout and did not require blood products. Donald and colleagues noted that a phase 2/3 clinical trial for patients with GD3 is anticipated in the second half of 2023.

“Following gene therapy, we have seen real changes in our life and our son's life,” the patient’s parent shared during a webcast presentation of earlier data in December 2022.2 “The first few weeks were a bit rough in terms of mucosal inflammation, hair loss and skin changes, but overall, he appeared to respond to the treatment very well. He is off ERT, steroids and SRT completely, with no return of PLE symptoms, such as edema and GI distress. He still has seizures but no further change in cognitive abilities. My son now is sleeping throughout the night, while he used to wake up often. Our family gained freedom as we are no longer tied to a challenging medication schedule and many hospital visits.”

Click here to read more coverage of WORLDSymposium 2023.

1. Donald A, Potter JE, Church HJ, et al. Sustained improvement of clinical CNS and somatic features of Type 3 Gaucher disease after haematopoietic stem cell (HSC) gene therapy: A first in world report. Presented at WORLDSymposium 2023, held February 22-26, in Orlando, Florida. Abstract #100
2. AVROBIO announces new positive clinical data and outlines clinical development plan following regulatory discussions for its Gaucher disease gene therapy. News release. AVROBIO. December 7, 2022. https://investors.avrobio.com/news-releases/news-release-details/avrobio-announces-new-positive-clinical-data-and-outlines
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