Abhimanyu Garg, MD, is a lipodystrophy specialist and professor and chief of the Division of Nutrition and Metabolic Diseases in the Department of Internal Medicine at UT Southwestern Medical Center. While at the NLA’s 2018 Scientific Sessions in Las Vegas, Nevada, he discussed the cofactors and concerns in familial chylomicronemia syndrome (FCS) treatments.
Garg: The other issue about gene therapy was, although I kept mentioning lipoprotein lipase as the cause of this disease, and that is true, deficiencies of this enzyme are co-factors, which play a role in effective working of the lipoprotein lipase enzyme, which can also be the underlying cause of familial chylomicronemia syndrome (FCS). So, there are several other genes that can cause the same FCS, and those are apolipoprotein C2, apolipoprotein A5, a long name that I’m not going to say but TPIHVP 1 is a short name for it, or lipase maturation factor 1.
So, the gene therapy was specific for lipoprotein lipase deficiency caused by mutations in the lipoprotein lipase gene but won’t work for the other four causes. So, what are the other efforts? Akcea is developing volanesorsen, which is an antisense protein apolipoprotein C3 therapy, which inhibits lipoprotein lipase. If we down regulate apolipoprotein C3, we would expect lipoprotein lipase activity to go up, and that can be beneficial for these patients. That is what they are trying right now. They have completed a Phase 3 study, but the final results of that have not been published.
These preliminary results, in the abstract form, have shown good efficacy—about 50% to 60% reduction in triglycerides values. At the same time, one has to look at the potential side effects of that therapy. Volanesorsen is promising as it has shown it can reduce triglyceride values by about 50% to 60% percent, but there are also potential side effects of this therapy. One of the worrisome side effects is lowering of the platelet levels, and I think in the primary data they reported that from was seen in five patients or more—I don’t remember exactly—but that is a cause of concern for this therapy.