More than half a dozen patients receiving a gene therapy for hemophilia A and another patient receiving a gene-edited cell therapy for beta-thalassemia showed encouraging early results, according to data announced Tuesday.
Brisbane, California-based Sangamo Therapeutics announced interim data from its Phase I/II study of SB-525 in hemophilia A and the first clinical data from a study of ST-400 in beta-thalassemia. SB-525 is an adeno-associated viral vector gene therapy that the company has partnered with Pfizer, while ST-400 is a cell therapy partnered with Sanofi that was developed using zinc finger nuclease, or ZFN gene editing.
The company additionally announced Tuesday an agreement with cell and gene therapy contract manufacturer Brammer Bio to secure access to large-scale adeno-associated viral vector manufacturing. It is also building its own cGMP plant, which it plans to open next year. The Brammer Bio deal will help it secure capacity for manufacturing therapies like ST-920, its gene therapy candidate for Fabry disease. Thermo Fisher Scientific announced a deal last week to acquire Brammer Bio for $1.7 billion.
Shares of Sangamo opened up 45 percent on the Nasdaq following the announcement Tuesday morning and were still trading up more than 26 percent in the afternoon.
Data from the SB-525 study included eight patients with severe hemophilia A and indicated that the therapy was generally well-tolerated and showed a dose-dependent increase in Factor VIII levels across all four dosage cohorts. In response, the company said, the trial’s safety monitoring committee recommended expanding the cohort of patients receiving the dose of 30 trillion vectors per kilogram of body weight. The other cohorts were receiving 900 billion, 2 trillion and 10 trillion vectors per kilogram. Six weeks after infusion, the two patients in the 30 trillion-vector cohort being expanded reached Factor VIII levels within the normal range, as measured by two different assays. One of those patients experienced serious side effects of hypotension and fever that were related to the therapy, but they resolved within 24 hours.
Cowen analyst Ritu Baral wrote that the SB-525 news was “very encouraging” and suggests and competitive risk/benefit profile for the therapy. Despite the small number of patients and relatively short follow-up leaving durability of response an open question, the expression levels are comparable to competitors and show little in the way of variation. Meanwhile, the benign safety profile could also provide a competitive edge. Spark Therapeutics – which Roche said in February that it would buy for $4.8 billion – has an adeno-associated viral vector gene therapy in Phase III development for hemophilia A, SPK-8011.
The patient with beta-thalassemia who received ST-400 showed successful editing of the gene responsible for the disease, as indicated by small insertions or deletions generated at the targeted DNA sequence known as indels. After infusion, the patient showed a rise in hemoglobin levels and, after a brief period of receiving regular blood transfusions, became transfusion-independent. The patient experienced a severe but transient allergic reaction that was related to a cryoprotectant in the product. ST-400 is an autologous cell therapy – similar to a CAR-T – that involves editing of the patients own stem cells using ZFN technology. While a form of genome-editing technology, ZFN is different in many respects from the more commonly used CRISPR/Cas9.
Baral wrote that while extremely early, the data are a solid proof-of-concept for the ability of Sangamo’s ZFN technology to edit cellular genomes ex vivo. While the allergic reaction was concerning, it appears to be an individual reaction rather than being treatment-related.
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