Sangamo Reaches Accord With FDA on Plans for Accelerated Approval Pathway for Fabry Disease Gene Therapy ST-920
The company noted that it expects to submit a BLA in the second half of next year.
Robert Hopkin, MD
Sangamo Therapeutics has emerged from a Type B interaction with the FDA having come into alignment with the agency on plans to pursue an accelerated approval pathway for isaralgagene civaparvove (ST-920), an investigational adeno-associated virus vector-based gene therapy product intended to treat Fabry disease.1
The company noted that based on the interaction it intends to use 1 year posttreatment estimated glomerular filtration rate (eGFR) slope data from patients treated in the ongoing phase 1/2 STAAR clinical trial (NCT04046224) as an intermediate clinical end point for a planned biologics license application (BLA) submission. The company noted that it expects to submit a BLA in the second half of next year and that the use of the accelerated approval pathway has potential to bring the therapy to market about 3 years sooner than a traditional approval pathway would allow for because an additional clinical trial will not be necessary. It also stated that the complete data set to be used to support the BLA will be reported in the first half of next year.
According to Sangamo, among 18 patients who were treated with ST-920 in STAAR who had greater than 1 year of follow-up a positive annualized eGFR slope emerged from statistically significant improvements in the mean and median eGFR levels that were recorded. The FDA noted that the eGFR slope at 104 weeks of follow-up may later be utilized for confirmation of clinical benefit.
“Fabry is a debilitating disease, for which there is a serious unmet medical need,” Sandy Macrae, MB, ChB, PhD, the chief executive officer of Sangamo, said in a statement.1 “I strongly believe in the potential for ST-920 to alleviate many manifestations of Fabry disease and am delighted to have a clear regulatory pathway that could bring this treatment to patients significantly sooner than originally anticipated”.
Earlier this year, Sangamo released data demonstrating disease improvements after treatment from 24 participants dosed in STAAR.2 The data were presented by investigator Robert Hopkin, MD, Cincinnati Children’s Hospital Medical Center, at the 2024 WORLDSymposium, held February 4-9, in San Diego, California. In 13 participants with at least 12 months of follow-up, Fabry outcome survey Mainz Severity Score Index improved (P = .0269), including 38% of participants on ERT. Renal function remained stable, and investigators observed statistically significant improvements on quality-of-life scores, General Health and Physical Component score, and gastrointestinal symptoms (all P <.03.).
Following the conference, CGTLive® interviewed Hopkin to learn more about unmet needs in Fabry disease and how the gene therapy may help to address these unmet needs. Hopkin emphasized the drawbacks of enzyme replacement therapy (ERT) and the potential benefit of a one-time treatment approach.
“Fabry disease is a rare, X-linked lysosomal storage disorder, and it affects multiple parts of the body,” Hopkin told CGTLive. “Some of the major complications are very high risk for heart failure, kidney failure and stroke. There's also severe chronic pain, gastrointestinal symptoms like diarrhea and constipation, that are sometimes severe enough to interfere with work. Current treatment requires a great deal of commitment from the patients and only partially addresses these needs. Patients will often lose up to half a day of their life every 2 weeks for enzyme infusions, or they have to take pills on a regular schedule, including fasting before and after taking the medicine. So that's a big burden on the patients. There’s a need to completely address the symptoms and the damage to the organs and trying to simplify the treatment, so it's less of a burden on the patients.”
