Biogen Idec (BIIB) encountered a setback this week, when a late-stage clinical trial of its drug to treat amyotrophic lateral sclerosis [ALS], also known as Lou Gehrig's disease, failed to show therapeutic benefits compared to a placebo. Perhaps in anticipation of this outcome, the company is repositioning itself to continue working with ALS drugs, by funding basic research on ALS at leading institutions and gaining a better handle on potential genetic factors behind the disease.
Biogen Idec in Weston, Massachusetts is a biotechnology company developing biologic therapies to treat neurodegenerative diseases, hemophilia, and autoimmune disorders. The company now offers treatments for multiple sclerosis, non-Hodgkin's lymphoma, rheumatoid arthritis, and psoriasis. In addition, Biogen Idec's development pipeline has therapies in clinical trials to treat relapsing and remitting multiple sclerosis, hemophilia, lupus, neuropathic pain, Alzheimer's disease and spinal muscular atrophy.
The clinical trial reported recently was a late-stage study of the drug dexpramipexole with 943 ALS patients. ALS is a neurological disease, that progresses rapidly and is usually fatal. The disease attacks nerve cells responsible for controlling voluntary muscles, and is characterized by the steady degeneration and death of motor neurons, ultimately causing paralysis throughout the body. The National Institute of Neurological Disorders and Stroke, part of NIH, says ALS affects people of all races and ethnic backgrounds, with as many as 20,000 to 30,000 people in the U.S. having the disease, and an estimated 5,000 new cases in the U.S. diagnosed each year.
Only one drug on the market is approved to treat ALS -- riluzole, marketed as Rilutek by Sanofi (SNY), and that has limited benefits. Tests of the drug against a placebo show Rilutek extends the lives of ALS patients on average by some 90 days. Dexpramipexole is a mitochondrial modulator that addresses the cells' power producers, called mitochondria, that convert energy into useful forms for the cells. Some neurodegenerative conditions are linked to mitochondrial dysfunction.
Early promise leads to later disappointment
Biogen Idec licensed dexpramipexole from its developer, privately-held Knopp Biosciences in Pittsburgh, following an earlier, smaller-scale trial of the drug with 102 ALS patients in 2011. The main objective of that study was to test for safety and tolerability, but the study also yielded early evidence that the drug could lower mortality and slow the decline of muscular functioning. Based on these preliminary findings, Biogen Idec went ahead with the larger trial of dexpramipexole.
In the more recent and larger-scale trial of dexpramipexole, the 943 ALS patients at 81 sites in 11 countries were randomly assigned to receive either the drug or a placebo in a process that masked to both the patients and clinicians which of the substances were being given. The results, measured by standard indexes of survival and loss of muscular functioning, showed no difference in outcomes between the patients receiving dexpramipexole or the placebo.
As a result of the clinical trial, the company abandoned further development of dexpramipexole. With few ALS drug candidates in other companies' pipelines, however, Biogen Idec is continuing with ALS drug research, but starting over almost from the beginning. In late December, the company recruited researchers from Yale, Harvard, Columbia, and Rockefeller universities in a $10 million, three-year project to identify new drug targets for ALS. Biogen Idec's chief scientist and professor at Harvard Medical School, Spyros Artavanis-Tsakonas, is bringing in for this project researchers in cell biology, molecular pathology, and genetics, as well as specialists in ALS.
In July, Biogen Idec announced a collaboration to investigate potential genetic factors behind ALS. That partnership engaged researchers at Duke University and HudsonAlpha Institute in Huntsville, Alabama to sequence the genomes of up to 1,000 patients with ALS over five years. The genomic sequencing data from the collaboration, says the company, will be shared with ALS researchers from University of Massachusetts, Stanford, University of Montreal, and Columbia.
A blog in the journal Nature Medicine discussed using genetic data to identify potential drug pathways for ALS following that publication's report of the Knopp Biosciences earlier-stage trial of dexpramipexole. The blog described new research that found mutations of protein-binding genes in about three percent of people with ALS, as another potential pathway for ALS drug therapies. Genetic studies could also indicate factors in the human genome that encourage or inhibit drugs like dexpramipexole on people with ALS.
The new Biogen Idec research strategy for ALS may indeed identify new drug targets and pathways, but it also underscores the risks of tackling this relentless and difficult disease, and translational medicine in general. Not only are potential drug candidates several years away, the experience with dexpramipexole shows even promising early results do not easily translate into marketable products.