Sangamo Therapeutics Inc. rolled out pleasing preliminary data from the first four patients treated in the phase I/II study known as Staar, evaluating isaralgagene civaparvovec, or ST-920, a gene therapy for Fabry disease.

Results as of the Sept. 17, 2021, cutoff date from the four patients in the first two dose cohorts showed that the drug was generally well-tolerated, and all four patients exhibited above normal alpha-galactosidase A (a-Gal A) activity. Boosted levels were maintained for up to one year for the first patient treated, and through 14 weeks for the most recently treated subject. Activity of twofold to 15-fold above mean normal was observed at the last measurement, Brisbane, Calif.-based Sangamo said.

The fifth patient in the study, who is the first patient in the third cohort (3e13vg/kg), was dosed after the cutoff date. The sixth patient is in screening, also for the third dose cohort. Based on the findings so far, the company has started planning for a phase III experiment. Shares (NASDAQ:SGMO) closed Nov. 4 at $10.89, up $1.75, or 19% on the news.

Withdrawal from enzyme replacement therapy (ERT) has taken place for one patient in Staar and is planned for the other patient who is on ERT, based on the stability of their a-Gal A activity following treatment. “We felt it was important to truly understand the effect duration, and we’ve been very pleased that over the course of the year in the longest-treated patients, there’s been a consistency of effect,” CEO Sandy Macrae said during a Nov. 4 conference call with investors. “We have discussions with investigators, and at the appropriate point for [such a] patient, they will withdraw treatment. The first patient was only withdrawn very recently, and the second one is timed to be withdrawn this year.”

As of the cutoff date, no treatment-related adverse events (AEs) higher than grade 1 had turned up, and no treatment-related serious AEs. No patients experienced liver enzyme elevations requiring steroid treatment.

The one patient with a significant elevation in plasma lyso-Gb3 pre-treatment showed significant reductions of about 40% (from baseline within 10 weeks after dosing, maintained through week 32) in this biomarker after treatment. Patients with low baseline levels of lyso-Gb3 maintained steady levels through the cutoff date, Sangamo said. “There’s only four patients, so it’s very difficult to say anything specific,” Macrae said, commenting on differences in responses among the patients. “It is notable, though, that patients one and four are on ERT, and patients two and three are not. It may be that there is some additional effect from the ERT that is leading to that effect, but that is only speculation and we need to dose more patients to understand it.” The main takeaway, he said, is that “all four patients have shown consistency of response in the time they’ve been observed,” although the company “need[s] to see the results of the third cohort to really be able to understand which dose we’re taking forward and how to design the [phase III] study.”

Jefferies analyst Maury Raycroft during the call focused on the hike in a-Gal A levels, which “seems higher than competitor data at month 12 that showed about five- to sixfold.” Bettina Cockroft, chief medical officer, said it’s too early to compare across programs. “We look forward to sharing more granularity on [these] data” during a scientific meeting next year.

Sangamo also disclosed that the FDA has put on clinical hold on the phase III Affine trial in hemophilia with gene therapy giroctocogene fitelparvovec, partnered with Pfizer Inc., of New York. Head of development for Sangamo, Rob Schott, explained the situation. “We have seen elevations of factor VIII greater than 150% in some patients,” he said. “This is an ongoing phase III trial, so we’re not being very specific with the data around it,” but no thrombotic hitches have surfaced. “The decision to voluntarily pause the trial was out of an abundance of caution. As anticipated, the FDA followed through with a clinical hold. We were notified of that late yesterday. Our plan with Pfizer [is] to submit a protocol amendment, have the discussion with the agency, and resume the trial when it is appropriate to do so.” Regarding the protocol changes, no details are being disclosed, Schott said. CEO Macrae said the company “feel[s] it is important to re-state every time that conversation comes up that no patient has come to harm. There have been no [AEs] related to this.”

Investors also learned that, while Sangamo and Paris-based Sanofi SA continue to advance the sickle cell disease program – they recently gained manufacturing requirements guidance from the FDA in preparation for further studies – the duo has quit development of ST-400 in beta-thalassemia. Mark McClung, chief operating officer, said the move was “a business decision that we took alongside our partners at Sanofi, just due to the timing and relative to where the competitive [data]set lies in terms of their development. We felt it was important to focus our effort and our resources solely on sickle cell disease.” ST-400 is an autologous cell therapy candidate that uses gene editing to modify a patient’s own hematopoietic stem cells to produce functional progeny red blood cells by increasing fetal hemoglobin.