ALS drug holds promise as Bennett leaves UVA
Five years after a small group of terminally ill patients pleaded with UVA for continued access to an experimental compound they believed could extend their lives, the UVA doctor who discovered the compound has left the university as mounting evidence suggests the drug is safe and, more importantly, that it may be effective against Amyotrophic Lateral Sclerosis, the deadly neurodegenerative disease also known Lou Gehrig's disease.
The latest good news about the compound known as “R-(+)-pramipexole" comes from Knopp Neurosciences, the Pennsylvania-based pharmaceutical company that took over development of the drug from UVA neurologist James Bennett in 2006.
Research has been ongoing at 20 sites around the country over the past two years, and Knopp announced August 11 that it will present the latest findings at a medical conference in Berlin in December. Knopp spokesperson Tom Petzinger says specific results won't be shared until the conference, but he describes them as "encouraging" enough that the company is now planning a Phase III study to begin by mid-2010.
If the drug is proven effective in the larger Phase III study, expected to take place at sites across America and in Europe, Knopp could then apply to the FDA for approval. For Bennett, the continued positive results are "beyond gratifying" even though he is no longer directly involved in the development and, in fact, has left UVA for Virginia Commonwealth University in Richmond, where he became head of the Neurology Department on July 1.
As reported in the Hook's February 24, 2005 cover story, "She's dying: His drug could save her," Bennett discovered the compound– the chemical mirror image of the Parkinson's drug Mirapex– on the shelf of a German laboratory in the mid-1990s. He hypothesized that the compound's ability to scavenge free radicals, molecules that cause cellular damage, could slow the progress of ALS, which is always fatal and which robs patients of the ability to walk, talk, and eventually to breathe.
While Mirapex possesses the same free radical scavenging abilities, at high enough doses, it causes unbearable side effects including nausea and even psychosis. Its mirror image, Bennett believed, might offer the benefits without the problems.
But despite his high hopes, Bennett's desperate patients soon learned that developing a drug is a complex, expensive, and time-consuming endeavor. Early obstacles included a UVA ethics committee cutting off human access to the compound until further safety tests were conducted on animals.
Following that late 2004 decision by the committee, Bennett's patients revolted, bombarding UVA and the FDA with letters pleading for permission to continue treatment.
"For a person with a terminal illness, risk is not the same as risk applied to a healthy person," explained then-53-year-old Norfolk resident Bob Echols, who had been diagnosed with ALS in 2003. "In a way, you're kind of beyond risk," said Echols. "If you have ALS, you're going to die, period."
Several months later, in spring 2005, Echols and the other patients were allowed to resume the medication under the FDA's so-called "compassionate use" policy, which allows the terminally ill access to medicines that have not yet been fully vetted. Since that time, all of Bennett's original patients have died, testimony to the relentless and devastating nature of the disease, which currently has no effective treatment.
Cathy Easter, Richmond-based spokesperson for the ALS Association, says her organization is following Knopp's research closely but is cautious about expressing optimism or discussing results of the study.
"We've tried to not encourage the open sharing of information to try to keep it more scientific," says Easter, recalling that during the early days of the drug's development, anecdotal positive results were attributed by the UVA committee to a placebo effect– in which patients taking ineffective medication believe they're getting better, despite any hard evidence– and Easter says some patients may have falsely gotten their hopes up. "We want the data to speak for itself," she explains.
Bennett, meanwhile, is now solely focused on his primary research expertise: Parkinson's, another neurodegenerative disease. He was recruited to VCU in large part by the Richmond-based Parkinson's support group Movers and Shakers, which raised enough money to endow a chair for him and who hope that his arrival will help make VCU a mecca for Parkinson's research.
In addition to heading up the neurology department, Bennett now also directs VCU's new $10 million Parkinson's research initiative. But despite his shift in focus– and jobs– Bennett hasn't given up on his drug. In fact, this year, he hopes to begin testing whether the compound could be effective against Parkinson's Disease as well, something he has long hypothesized.
He's quick to downplay his own role in the potential success of the compound, however.
"I'm more stubborn than smart," he says, noting that his experiences developing the drug, however frustrating at times, highlight the importance of government funding for health research, such as the grants he received from the National Institutes of Health for his early research into pramipexole.
"Putting aside anything I did," he says, "it's a success story in terms of how taxpayer money into the NIH can generate something that might be of help to people with a disease."