The drug Iplex, developed by the Richmond, Va., biopharmaceutical company Insmed, did not improve muscle function, strength or endurance in a phase 2 trial in type 1 myotonic dystrophy (MMD1, or DM1), the company announced June 25, 2009. (See Insmed Announces Results.)
No conclusions were reached about the effect of Iplex on cognitive function, gastrointestinal function or pain, because of a limited number of trial participants with problems in these areas.
However, measurements of insulin sensitivity -- the ability of cells to respond to insulin -- did show improvements in trial participants. Insulin sensitivity was assessed by serum levels of glucose and insulin, as well as cholesterol and triglycerides.
MDA helped support the clinical trial, which involved 69 adults with MMD1 who were randomly assigned to receive either Iplex or a placebo for six months. Neither participants nor investigators knew who received the drug until after all data had been collected.
Insmed said it plans to apply to MDA for further support to test Iplex in a subset of MMD patients who show severe insensitivity to insulin (insulin resistance).
Sharon Hesterlee, MDA senior vice president and executive director of MDA Venture Philanthropy (MVP), said she looks forward to evaluating the company's application.
About insulin resistance in MMD1
A varying degree of resistance to insulin by muscle cells contributes to the problems seen in type 1 MMD, a multisystem disease involving weakness and myotonia (inability to relax muscles properly) of skeletal muscles, as well as cardiac abnormalities, metabolic abnormalities, and other effects.
Insulin resistance in MMD1 is due to abnormalities in construction of the so-called insulin receptors, the molecular "landing pads" for insulin on muscle fibers, in this disease.
In MMD1, insulin resistance may contribute to muscle weakness and wasting. In severe cases, insulin resistance can cause diabetes-like symptoms, but this is rarely the case in MMD1.
Iplex is a combination of a protein called insulin-like growth factor 1 (IGF1) and IGF binding protein 3. It was approved in the United States in 2005 for treatment of children with growth failure due to severe deficiency of IGF1. (Insmed no longer markets Iplex for this purpose in the United States after losing a patent dispute.)
In March 2009, Insmed received permission from the U.S. Food and Drug Administration (FDA) to test Iplex for use against amyotrophic lateral sclerosis (ALS). (See FDA to Allow Testing of Iplex in ALS.) The use of IGF1-based treatment of ALS has some scientific plausibility, but other formulations of IGF1 have not shown success in clinical trials in this neurodegenerative disease. (See IGF1: Failure or Success as an ALS Therapy?)