Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of preliminary data from the Phase 2 clinical trial of its ZFP Therapeutic(TM) program to develop SB-509 as a treatment for amyotrophic lateral sclerosis (ALS) at a Work in Progress session at the 20th International Symposium on ALS/MND held in Berlin, Germany.
The preliminary data were from the first subjects enrolled in Sangamo's Phase 2 clinical trial, SB-509-801, and demonstrate an approximate doubling of frequency of improved muscle function in subjects with ALS who received two treatments of SB-509 (32%) compared to matched historic controls (17%). In early stage ALS clinical trials, an historic control is frequently used rather than a placebo to maximize the number of subjects receiving the drug.
Muscle function was assessed by muscle manual testing (MMT), a commonly used ALS endpoint which uses a manual method of functional assessment of 34 muscles over the whole body. In addition, a subset of subjects that showed an increase in muscle function over this period also demonstrated improvement in one or more additional end-points. These end-points include the Revised ALS Functional Rating Scale (ALSFRS-R) which is a validated rating instrument for monitoring the quality of life and progression of disability in patients with ALS and whose scores correlate significantly with survival, and forced vital capacity (FVC), a measure of lung function.
"We desperately need new therapeutics that will alter the relentless deterioration of muscle function that is characteristic of ALS," commented Jeffrey Rothstein, M.D., Ph.D., Director of the Robert Packard Center for ALS Research, Co-Director of the MDA/ALS Clinic and professor of Neurology at the Johns Hopkins University School of Medicine. "The ability to maintain muscle strength or delay its deterioration could have a significant impact on quality of life for persons with ALS."
SB-509 is a transcriptional activator of vascular endothelial growth factor (VEGF-A) which has been demonstrated to have a significant role in ALS. Mutations that reduce levels of VEGF-A expression are linked with progression to ALS and VEGF-A levels are reduced in the spinal fluid of patients with ALS. In addition, in an apparent compensatory response, VEGF receptor levels are increased in both the blood vessels and the spinal cord in ALS patients.
"Preclinical data as well as clinical observations from our studies of SB-509 in diabetic neuropathy demonstrated that this ZFP Therapeutic has an effect on muscle function and we are very pleased to see evidence of a similar effect in subjects with ALS," stated Dale Ando, M.D., Sangamo's Vice President of Therapeutic Development and Chief Medical Officer. "Our primary goal for this study was to assess the safety and tolerability of SB-509 in subjects with ALS and to evaluate a dosing schedule and pattern of drug administration as well as to look for indications of efficacy of the drug. At this point we have full data sets from only a handful of the subjects enrolled in the trial and thus have not completed a full analysis of all of the endpoints. Significant improvements in muscular function have not been seen in previous ALS trials. Any progress in this endpoint may translate into an important benefit in the quality of life of these patients. The drug continues to have an excellent safety profile and these initial results are encouraging not only for ALS but potentially for application in other neuromuscular diseases such as dystrophies and myopathies."
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