In response to testimony by physicians such as MUSC's Michelle Hudspeth, M.D., about the impact of drug shortages on patient care, Congress, in a rare show of bipartisan cooperation, passed the Food and Drug Administration Innovation and Safety Act on June 26 and President Obama signed it into law on July 9.
The legislation has wide-ranging implications not only for the nation's ability to respond to potential drug shortages but also for streamlining the drug development pathway for promising new drugs.
The July/August issue of Progressnotes examines the implications of this legislation in more detail and profiles novel therapies currently making their way through the clinical trials process at Hollings Cancer Center, including a first-in-human phase 1 trial of a new class of drugs (sphingosine kinase inhibitors [SKIs]). Sphingosine kinase and ceramide are key players in a biological control mechanism that determines whether cancer cells die (ceramide) or survive (sphingosine kinase) and prove resistant to chemotherapy and radiation. By blocking sphingosine kinase, SKIs may tilt this control mechanism toward cancer cell death. It is speculated that administering an SKI along with a chemotherapy drug or radiation could make cancer cells more vulnerable and less likely to develop resistance to such treatments. The new legislation could mean that patients benefit sooner from such promising, innovative therapies.
This legislation takes several important steps to alleviate the current drug shortage and to prevent future ones. Most notably, perhaps, it requires manufacturers of generic drugs to pay user fees to the US Food and Drug Administration (FDA). The FDA uses the funds to speed approval of new generic drug applications and to expedite inspection and reinspection of production lines.
Once thought to merely serve as structural components of the plasma membrane, sphingolipids are major actors in pathways that lead to angiogenesis, inflammation, as well as cancer development and resistance to chemotherapy and radiation.
Ramping up inspections at foreign plants is particularly important to ensure quality in an age of outsourcing. Manufacturers will also be required to provide the Secretary of Health and Human Services six months' notice of the suspension or closing of a production line that could lead to a drug shortage so that the FDA can take steps to avert it.
Finally, the legislation addresses the growing problem of counterfeit drugs, hiking the maximum sentence for counterfeiters from three to 20 years in prison and the maximum penalty from $10,000 to $4 million.
This legislation also streamlines the approval process for "breakthrough therapies," marking the first significant change to the FDA's drug development pathway since 1997. Before this legislation, new, promising drugs could take a long time to reach the market and the patient because new drug approval hinged on evidence from large, multisite phase 3 trials of statistically significant survival benefit over current treatment options.
Such trials are expensive, long and complex. Demonstrating survival benefit requires that studies enroll hundreds or thousands of patients and continue until enough control patients have died to reach statistical significance. By relaxing the requirement for demonstrated survival benefit for breakthrough drugs and allowing instead one of any number of clinical end points to serve as a surrogate of efficacy, this legislation will result in shorter, less expensive clinical trials enrolling fewer patients. As a result, promising new therapies will reach patients sooner.
Close follow-up of breakthrough drugs receiving such streamlined approval will be required, and the FDA can pull any of these drugs off the market quickly if their efficacy is less than expected or if unexpected side effects occur.
The online version of the July/August issue of Progressnotes can be found at http://www.MUSChealth.com/progressnotes. In this issue, you can also read about:
- Michael Lilly, M.D., a noted urologic oncologist and translational cancer researcher, recently assumed the position of associate director for translational research at MUSC's Hollings Cancer Center. Lilly comes to MUSC from the University of California, Irvine, where he served as the vice chief for clinical programs of the Division of Hematology-Oncology and coleader of the Translational Oncology Program at the Chao Family Comprehensive Cancer Center;
- How patients with a severely blocked aorta who are not candidates for surgical intervention can lead longer, active lives after transcatheter aortic valve replacement;
- How patients who have long suffered from the debilitating pain of chronic pancreatitis can gain a new lease on life by having their pancreas removed and, to guard against brittle diabetes, have their own insulin-making islet cells harvested from the pancreas and reinfused into their liver; and
- How modern burn management techniques and support services offered by MUSC's pediatric burn center can restore even badly burned pediatric patients to a good quality of life.
Editor's note: "Progressnotes" is a bimonthly publication produced by Business Development & Marketing Services and sent to all physicians licensed in South Carolina to inform them about clinical and research innovations at MUSC. For information, email firstname.lastname@example.org.