Testimony before the Food and Drug Administration Endocrine and Metabolic Drugs Advisory Committee Meeting on pramlintide (Symlin), recommending that it not be approved and that no additional clinical trials be done (HRG Publication #1584)
Statement by Sidney M. Wolfe, MD ,
FDA Endocrine and Metabolic Drugs Advisory Committee Meeting on Pramlintide (SYMLIN, Amylin Pharmaceuticals)
July 26, 2001
As endocrinologists or primary care physicians, would we recommend, for our insulin-requiring diabetic patients, a drug that had the following benefits and risks in randomized placebo-controlled studies?
Average lowering of HbA1c---compared to placebo---of only 0.3% in the four fixed-dose studies. (9% to 8.7%) (Type I and II diabetes); for most patients, this is well short of the 7% ADA goal and the 8% goal for obviating further (other) treatment.
Increased severe hypoglycemia with automobile driving-related adverse events including crashes and confusion while driving (statistically significant); most people required paramedic intervention, ER visits and IV glucose administration; there was one death in an auto crash in a patient getting pramlintide. (Type I)
Nervous system problems: 11 out of 1179 patients given pramlintide and none out of 538 given placebo (statistically significant); 4 of the 11 patients had convulsions, 3 with coma and one each with, ataxia, headache, vertigo and migraine (Type I)
Type I: Nausea: 51% pramlintide vs. 17% placebo; Anorexia: 18% vs. 2%
Type II: Nausea: 24% pramlintide vs. 14% placebo; Anorexia: 8% vs. 3%
(All four of these comparisons highly statistically significant)
Diabetic retinopathy: in the high dose group (adjusted insulin) there was an increase (19%) in retinopathy in Type II diabetics compared to the placebo group (8%)
Need for more injections: since the drug can not be mixed with insulin, the number of injections for users would increase from one or two per day to between three and five or more injections per day
If the answer to the question about recommending this drug for our own patients is no, because the risks so clearly outweigh the benefits, the answer to the question about whether the FDA should approve the drug must also be no, as concluded by FDA Medical Officer Dr. Robert Misbin.
Beyond the question of FDA approval, however, is the issue of any further clinical trials, such as those proposed by the FDA. Based on existing knowledge about serious risks caused by pramlintide, it would be unethical to do a study to pin down more firmly the causal relationship of this drug to hypoglycemia unawareness, to further study efficacy or to expose patients for any other purpose. One can only imagine what the informed consent sheets for such studies would have to look like. This drug deserves to be put out of its misery before any more patients are injured or killed in any further clinical trials.