Nov. 11, 2008

'Tie-Breaker' Myotrophin Trial Negative in ALS

A nationwide team of investigators representing 21 U.S. centers announced Nov. 5 at the 19th International Symposium on ALS/MND in Birmingham, UK, that Myotrophin, injected subcutaneously (under the skin), does not slow the progression of weakness, prolong survival or slow functional deterioration for people with ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

ALS destroys the nerve cells controlling muscles, ultimately causing complete paralysis while leaving mental function intact. Survival is typically two to five years after diagnosis, and no cure exists.

Myotrophin is the brand name for a type of neurotrophic factor (proteins responsible for the growth and survival of neurons) called IGF1, or insulin-like growth factor 1, developed by the pharmaceutical company Cephalon (Frazer, Pa.) and its partner Chiron (Emeryville, Calif.). 

With funding from the National Institutes of Health, investigators injected IGF1 at doses of 0.05 mg/kg body weight or a placebo twice daily in 330 people with ALS.  

Patients were randomly selected to receive either the drug or placebo; neither they nor the investigators knew who received which. Measurements of muscle testing scores, survival rates and ALS Functional Rating Scale-Revised (ALSFRS-R) revealed no differences between the treatment and placebo groups.

Previous human clinical trials of Myotrophin in ALS have been inconsistent. One large study in North America suggested a beneficial effect as measured by the Appel ALS rating scale that measures loss of function over time. A large European study failed to demonstrate benefit. The contradictory results prompted the U.S. Food and Drug Administration to then recommend a tie-breaking trial.

"We were left with one 'good' study and one 'failed' study -- with the latter possibly due to unequal baseline stratification of patients -- and a third study was truly needed," said study investigator and MDA grantee Stanley H. Appel, who also served as an investigator in the earlier North American Myotrophin trial. A neurologist and longtime MDA grantee, Appel is director of the MDA/ALS Center at the Methodist Neurological Institute in Houston and serves as chairman of the Association's Medical Advisory Committee.

Appel noted that IGF as therapy may still have potential with a different route of administration such as viral vector or stem cell delivery, but "This trial settles the question as to whether injection of IGF1 in this form has a significant clinical benefit."