Boston, Mass. (Apr. 1) - Despite a relative paucity in the current analgesic pipeline, a greater understanding of complex pain processes, pharmacogenetics, and new diagnostic tools and therapeutic targets, including assays and biomarkers, may open the doorway to more effective therapies, as well as better use of existing treatments, according to experts speaking here at the 24th Annual Scientific Meeting of the American Pain Society.
In the post-genomic era, part of the response to pain comes from a genetic influence, says, Raymond A. Dionne, PhD, DDS, at the National Institute of Dental and Craniofacial Research in Bethesda, Maryland. Identifying subgroups or responders may help maximize the efficacy of new and existing drugs.1
CIAOMed recently reported that rheumatoid arthritis (RA) patients with a particular allele of tumor necrosis factor alpha (TNF-α) respond better to etanercept therapy than their counterparts without the single-nucleotide polymorphism (SNP).2 This study appeared in the April issue of the journal Rheumatology.
"The genotyping of candidate SNPs associated with pain and inflammation and development of sensitization may identify various pathways or targets for analgesic development that are not so clear right now," Dr. Dionne says.
American Pain Society president Dennis C. Turk, PhD, an anesthesiologist at the University of Washington in Seattle, Washington, agrees that such personalized medicine is the wave of the future. "The days of one-size-fits-all medicine are over," he says. "Not everyone response to opioids-we need to know why."
Obstacles in pharmaceutical development
The dearth of new pain drugs is largely due to failure to translate increasing understanding of pain into improved therapies, Dr. Dionne says. From 1980 to 2000, 48 drugs were approved with analgesic indications - including opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and combinations/reformulations, or different routes of administration, he says.
Impediments to the development of novel analgesics include complex pain processes versus very specific analgesic drug mechanisms, complex regulatory requirements, and pain researchers who are not sure how to screen drug candidates, Dr Dionne explains.
For example, "How do you extrapolate from clean clinical models to heterogeneous diseases and patients?" he asks. He tells CIAOMed that initial steps should include abandoning the quest for the holy grail of analgesic drug specificity.
In addition, Dr. Dionne continues, "we need new tools including assays, computer modeling techniques, biomarkers, and clinical trial endpoints to identify products earlier in the process that don't hold promise and facilitate the development of medical products with the most promise for patients."
Specifically, a new drug entering phase I testing has an 8% chance of reaching the market-down from a historical success rate of 14%, Dr. Dionne says.
Will there be a drug discovery renaissance?
"My opinion is that the pipeline is dry [but] it may be just more dormant than dry even though we are in the Decade of Pain Control and Research," says Joseph W. Stauffer, MD, vice president of Global Medical Affairs at Alpharma Inc in Fort Lee, New Jersey. Congress declared 2000-2010 as the Decade of Pain Control and Research.
In terms of pain medications, every therapy is a derivative of willow bark, opium poppy, or an epilepsy drug. Dr. Stauffer remarks, "We are halfway through the decade of pain control and research and we don't have too much that's new."
This is true despite the fact that the United States spends twice as much money on pharmaceutical research and development as do other countries, Dr. Stauffer says. "Yet over the last 25 years new drug applications (NDAs) have gone down while spending has increased." There was an increase in NDAs in 2004, however, though some may simply be new formulations or new salts of an old drug.
Much of this is due to failures in the clinical and translational research, Dr. Stauffer says. "We want more phase IV marketing studies and products that fail better and quicker in phase I."
Paul Desjardins, DMD, PhD, senior vice president of Scirex Corporation in Austin, Texas, says that in the post-coxib era, "the big bird has been knocked off the perch, [but] there is a huge opportunity now. The pipeline is not dry; the spigot has just opened."
Another way to revive the inertia in the analgesic drug pipeline is through public-private partnerships, such as the Osteoarthritis Initiative (OAI), Dr. Dionne adds. The OAI is a public-private partnership between the National Institutes of Health and the pharmaceutical industry that funds a multi-institutional project to advance the discovery of biological markers for osteoarthritis.
References:
- Dionne RA. Is the analgesic drug development pipeline drying up? The challenge of developing novel analgesics. Presented at: 24th Annual Scientific Meeting of the American Pain Society; March 30-April 2, 2005; Boston, Mass. Session 313.
- 2. Kang CP, Lee KW, Yoo DH, et al. The influence of a polymorphism at position -857 of the tumour necrosis factor alpha gene on clinical response to etanercept therapy in rheumatoid arthritis. Rheumatology. 2005;44:547-552.