This is part 1 of a 2-part series on the Critical Path Initiative, Alzheimer's disease, and breast cancer.
How often have you heard about a molecule or other therapeutic breakthrough discovered in the lab that has the potential to shift the standard of care or change the very treatment paradigm for a disease? An effective preventive treatment for Alzheimer’s disease, a potential universal “cure” for cancer, a psychotropic drug that effectively addresses depression and continues to work without side effects—the list of ostensible breakthroughs is vast.
So what happens to these potential miracle meds?
If these discoveries ever advance beyond the preclinical stage to human clinical trials, 90% of them fail either because of lack of efficacy, or safety, or both. The odds improve once a drug achieves positive phase 2 results. At that point, it has a 50% change of success during phase 3. Nonetheless, the process of getting to phase 3, funding continued research and development (R&D), navigating the regulatory landscape, and anticipating post-marketing surveillance requirements in advance is time consuming and expensive.
The cost of developing a new drug ranges from $350 million at the very low end to almost $7 billion per drug at the high end. Overall, per-drug development costs now average $5 billion. There is also the problem of time: a 10-year development timeframe is now the norm.
For years, there has been hand-wringing over the enormous financial and time investments necessary to bring a drug to market. But there have been notable improvements—most of them developed by the FDA. One such improvement is the fast track designation system that allows companies to request Fast-Track designation, Priority Review, or Accelerated Approval from the FDA to shorten the development time frame and get much-needed support.
Alhough there are various criteria for this system, overall, obtaining one of the fast-track designations requires a drug to address an unmet medical need or represent a substantial improvement over other available treatment options.
The Critical Path Initiative
Fast-tracking has been good for companies, allowing them to shorten development timelines and get drugs to patients faster; however, the benefits are accrued on a company-by-company, drug-by-drug basis.
By contrast, the Critical Path Initiative, introduced by the FDA in 2005, has a broader reach and takes a larger view of the overall development process as it relates to the U.S. approval process. The Critical Path Initiative was developed to improve the methods used to move drugs from the lab to the patient in a more efficient manner.
The Critical Path Initiative (C-Path) was conceived in May 2004 when the FDA published a report entitled, “Innovation or Stagnation, Challenge and Opportunity in the Critical Path to New Medical Products.” The goal, as outlined in this landmark report, is to use innovative methods to ensure that researchers developing new drugs are able to leverage the latest technology, along with existing knowledge culled from relevant clinical trials, scientific expertise, and collaborative interaction between industry, academia, regulatory agencies, and patient advocacy groups.
Together these groups, known as C-Path Consortia, ask the big-picture questions about drug development. What are the best methods for testing drug safety and efficacy in a therapeutic area? Are there any biomarkers that can be used as suitable endpoints to expedite the development process? How can we share clinical trial data without compromising patient privacy?
A breakthrough for Alzheimer’s disease trial design
These questions often yield interesting and useful answers. For example, in July 2013, the Coalition of Major Diseases (CAMD), one of the eight consortia developed by C-Path, received good news from both the FDA and the European Medicines Agency (EMA). Both agencies approved the Alzheimer’s disease (AD) Simulation Tool developed by the CAMD, which was designed to improve trial design in mild-to-moderate AD.
The AD Simulation Tool uses computerized models to simulate “what-if” scenarios for clinical trials. It includes data from more than 6,000 unnamed patients who have been involved in AD trials. For end-users, that means being able to use aggregated knowledge to better understand disease progression, drug effects, placebo effects, and potential sources of variability.
Collaboration and innovation + Alzheimer's breakthrough?
The simulator tool is available to any company that is developing AD therapies or diagnostics. Currently, there are approximately 5.4 million people in the United States living with Alzheimer’s disease—a number that is expected to swell to 16 million by 2050. There have been more than 100 AD drug-development failures in the last 15 years.
But recently, there has been progress. Researchers who used to rely on cognitive tests and post-mortem brain analysis now have access to simulated data, courtesy of C-Path.
One day, there will be a news report about a treatment for AD that makes it through phase 3 and becomes part of the new standard of care. It’s not clear when that will be; but what is clear is that it will not be the work of one company alone, but rather a collaborative effort of many companies held aloft by knowledge culled from years and years of hard work.
To learn more about C-Path's Alzheimer's Disease Simulation Tool, click here.
In part 2 of this series, BioPharma Dive will explore the impact of C-Path on breast cancer clinical trial design.