AVROBIO Announces First Patient Dosed in Phase 1/2 Trial of Gene Therapy for Cystinosis
Investigational Therapy Designed to Engineer Patients’ Own Stem Cells to Produce Essential Protein
The trial will enroll up to six patients with cystinosis, a rare inherited disease caused by a defect in the gene that encodes for cystinosin. The cystinosin protein enables transport of the amino acid cystine out of lysosomes. When it is absent, cystine accumulates and crystalizes, causing progressive damage to the kidneys, liver, muscles, eyes and other organs and tissues. Cystinosis affects both children and adults; they face shortened life spans and often painful symptoms, including muscle wasting, difficulty breathing, blindness and kidney failure.
“Cystinosis is a debilitating and progressive disease, and new treatment options are sorely needed. The current standard of care does not avert deterioration; at best, it can attenuate symptoms. That’s why gene therapy is particularly exciting: It has the potential to change the course of disease -- and the lives of patients -- by addressing the underlying cause of cystinosis,” said
The single-arm trial will enroll four adults and a potential follow-on cohort of two adults or adolescents at least 14 years of age who are currently being treated with cysteamine, the standard of care for cystinosis. If started at an early age and taken on a strict dosing schedule, cysteamine can delay kidney failure. However, the treatment regimen is highly burdensome, with side effects that can be severe and unpleasant, and many patients find it difficult to adhere to this treatment regimen. Even if compliance is high, cysteamine therapy cannot prevent kidney failure or avert other complications.
“For people with cystinosis, there are no healthy days. They must take dozens of pills a day, around the clock, just to stay alive. It is a relentless disease and we urgently need new treatments,” said
The trial’s primary endpoints are safety and tolerability, assessed for up to two years after treatment, as well as efficacy, as assessed by cystine levels in white blood cells. Secondary endpoints to assess efficacy include changes in cystine levels in the blood, intestinal mucosa and skin and cystine crystal counts in the eye and skin. Efficacy will also be evaluated through clinical tests of kidney function, vision, muscle strength, pulmonary function and neurological and psychometric function, as well as through assessments of participants’ quality of life after treatment. The trial is funded by grants to UC San Diego from the
“This investigational gene therapy starts with the patients’ own stem cells, which are genetically modified so that their daughter cells can produce and deliver functional cystinosin to cells throughout the body. With this approach we aim to prevent the abnormal accumulation of cystine that causes so many devastating complications,” said
AVR-RD-04 is a lentiviral-based gene therapy designed to potentially halt the progression of cystinosis with a single dose of the patient’s own hematopoietic stem cells. The stem cells are genetically modified so they can produce functional cystinosin with the aim of substantially reducing levels of cystine in cells throughout the patient’s body. Before the infusion of the cells, patients undergo personalized conditioning with busulfan to enable the cells to permanently engraft. The Phase 1/2 clinical trial is being conducted under the name CTNS-RD-04 by AVROBIO’s academic collaborators at the
Cystinosis is a rare, inherited lysosomal storage disorder characterized by the accumulation of cystine in all the cells of the body, resulting in serious and potentially fatal damage to multiple organs and tissues and the shortening of patients’ life spans. The kidneys and eyes are especially vulnerable; more than 90% of untreated patients require a kidney transplant before age 20. An estimated 1 in 170,000 people are diagnosed with cystinosis.
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Christopher F. Brinzey
Westwicke, and ICR Company
Ten Bridge Communications