Drug development doesn’t get much more depressing than the so-far futile search for a lasting treatment for amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. More than 20 experimental drugs have failed in clinical trials, the most recent being Biogen Idec’s (NASDAQ: [[ticker:BIIB]]) closely watched dexpramipexole. Dex, as it is often called, made it all the way to a 943-patient, Phase III trial, one of the largest clinical trials yet in this disease, but still did not show any benefit for patients, and Weston, MA-based Biogen announced last week that it will drop all development of the drug.
So what lessons, if any, do all these flame-outs hold for the handful of drugs still in development against this deadly disease? Steve Perrin, CEO of the nonprofit ALS Therapy Development Institute in Cambridge, MA, has one suggestion, but it won’t be of much comfort to companies struggling to finance and recruit patients for clinical tests for this rare and deadly disease. Nor is it likely to get Big Pharma companies to reach into their deep pockets and fund drug development for a disease that seems to produce nothing but heartache. Perrin posits that mid-stage Phase 2 trials must be larger, and longer, than they are now if companies want to determine the best way forward in a Phase 3 trial.
“All of the drugs that have failed recently in Phase 3 looked promising at Phase 2. Dex slowed down the disease in over 30 percent of the patients in the Phase 2b trial,” Perrin told me in a phone interview. “The lesson here is that we need to change the design in Phase 2,” especially if companies plan to test the drug in different doses. There were only 102 patients in Biogen Idec’s Phase 2 trial; dividing a group this small into two or three subgroups means the cohorts “are just not big enough to reach significant conclusion about the data,” Perrin said.
The problem is, ALS affects a mere five out of every 100,000 people worldwide, and there are only 30,000 people living with the
disease in the U.S., making it exceedingly difficult to recruit enough patients to enroll in a large Phase 2 trial—especially if multiple
