A single infusion of AVR-RD-02, Avrobio’s experimental gene therapy for Gaucher disease type 1, was able to lower the levels of two disease biomarkers within three months in the first patient dosed in an ongoing Phase 1/2 trial, the company said.
The investigational therapy also was safe and well-tolerated, causing no serious nor unexpected side effects.
Early data from the trial, called GuardOne (NCT04145037), were shared by the company in a press release, in which Avrobio announced the launch of a new clinical program for Gaucher disease type 3 — which affects about 5% of patients — and the expansion of its current gene therapy pipeline to six genetic lysosomal disorders.
“As we move into the next stage of company growth, we’re expanding our lysosomal disorder pipeline with a new program for Gaucher disease type 3 and we plan to dose the first Hunter syndrome patient next year,” said Geoff MacKay, president and CEO of Avrobio.
“We expect to be the first lentiviral gene therapy to the clinic across all six of these indications — and in some cases, the first to be in the clinic with an investigational gene therapy of any type,” MacKay said.
In addition to these program updates, the company announced new positive data across its gene therapy programs for Fabry disease and cystinosis, two other lysosomal disorders. According to Avrobio, the company is now in a vantage position to be able to bring these innovative gene therapies to the clinic.
“We believe the new data we’ve announced today help de-risk our portfolio which leverages the same lentiviral gene therapy approach across indications,” MacKay said. “With strong clinical trial enrollment momentum coming out of the COVID-19-related slowdown, we anticipate dosing, enrolling or consenting five patients across our clinical trials this quarter, and dosing a total of 30 patients cumulatively across our clinical programs by the end of 2021.”
Lysosomal disorders are caused by a genetic mutation that leads to the buildup of toxic substances inside cells’ lysosomes — small compartments that accumulate, digest, and recycle materials.
AVR-RD-02 uses a harmless lentiviral vector to insert a functional copy of the GBA gene, which is faulty in people with Gaucher, inside patients’ own blood cell precursors, also known as hematopoietic stem cells. Through this mechanism, AVR-RD-02 is expected to permanently restore the production of beta-glucocerebrosidase (GCase) — the enzyme normally produced from the GBA gene — and lower the accumulation of fatty toxic substances inside cells.
The gene therapy candidate was previously named an orphan drug for the treatment of Gaucher type 1, which affects nearly 90% of all people with the disease, by both U.S. and European regulatory authorities.
The safety and efficacy of a single infusion of AVR-RD-02 are currently being assessed in GuardOne, a Phase 1/2 trial that is still recruiting participants at the Royal Melbourne Hospital, in Australia, and at the University of Calgary, in Canada.
The trial’s main goals include assessing treatment-related side effects, as well as evaluating the gene therapy’s effects on GCase activity, both of which will be evaluated over one year following dosing.
Avrobio now announced three-month data from the first patient dosed in the study. This participant discontinued ERT one month after receiving AVR-RD-02 and is currently off such treatment.
Up to Nov. 3, AVR-RD-02 was safe and well-tolerated, and did not cause any serious nor unexpected side effects to this patient in the first three months following dosing. Of note, the patient’s hemoglobin levels — levels of red blood cell proteins — and platelet counts, which tend to be low in people with Gaucher, remained within a normal range in this period.
In addition, the patient saw her levels of glucosylsphingosine (lyso-Gb1), a Gaucher disease biomarker, drop by 22% compared with a baseline (study start) measurement taken while she was still receiving ERT.
A 17% drop in the levels of chitotriosidase — a biomarker of activated immune cells, also known as “Gaucher cells” — also was observed in the same period of time. Gaucher cells contain high levels of toxic substances that infiltrate different tissues and organs.
Top-line data from GuardOne are expected by May 2021 and the trial is scheduled to conclude in September 2022.
Avrobio also announced the launch of its clinical development program of AVR-RD-06, which will use the same lentiviral vector as AVR-RD-02, for Gaucher disease type 3. The company hopes the new therapy may help alleviate the neurological symptoms of the disease by replacing the Gaucher cells with healthy immune cells derived from the genetically modified blood cell progenitors gathered from patients.
“We believe the opportunity we have to potentially prevent patients, especially children, from developing the disabilities that would otherwise result from their inherited genetic code — to perhaps give them the possibility of a full and healthy life — is humbling,” said Chris Mason, MD, PhD, chief scientific officer at Avrobio.
“That is our purpose; it drives all of us at AVROBIO every day,” Mason added.