Key Updates from the Food and Drug Administration
FDA Oversight of Tobacco Products
previous issue of the
Cancer Policy Monitor, we informed our readers about the U.S. Food and Drug Administration's (FDA) plans for a comprehensive regulatory plan for tobacco and nicotine regulation through a cohesive, agency-wide approach to nicotine. Since then, the
New England Journal of Medicine published a perspective on
A Nicotine-Focused Framework for Public Health by FDA Commissioner Scott Gottlieb, MD, and
Center for Tobacco Products Director Mitchell Zeller, JD, outlining this plan and the effort to lower nicotine levels in combustible cigarettes to non-addictive levels.
In the article, Commissioner Gottlieb and Director Zeller discuss the potential for e-cigarettes to serve as smoking cessation devices, saying that "there are already products, such as electronic nicotine delivery systems, that could conceivably deliver nicotine without posing the dangers associated with tobacco combustion." They did acknowledge that there are currently opposing views on potential risks and benefits of e-cigarettes, adding that "we must continue to build on our understanding of the potential benefits for addicted cigarette smokers, in a properly regulated marketplace, of products capable of delivering nicotine without having to set tobacco on fire."
Last year, the AACR released a webinar titled "E-cigarettes: Research, Public Health Concerns, Opportunities, and Regulations," which you can
FDA Approves First Gene Therapy in the U.S.
In other news, the FDA
approved the first gene therapy in the United States, Kymriah (tisagenlecleucel), for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL). Elizabeth M. Jaffee, MD, president-elect of the AACR and deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, was quoted in the
Washington Post and
Baltimore Sun stories about the FDA's approval of Kymriah.
Below is an excerpt from the Cancer Research Catalyst, the AACR's official blog, about this revolutionary treatment:
The CAR T-cell therapy in question is tisagenlecleucel (Kymriah). Known through most of its development as CTL019, tisagenlecleucel was approved for treating certain pediatric and young adult patients with acute lymphoblastic leukemia (ALL). Specifically, it was approved for treating children and young adults up to the age of 25 with B-cell ALL that is refractory, meaning that it has not responded to standard treatments, or has relapsed at least twice.
Tisagenlecleucel is a cell-based therapy that targets CD19-positive cells. Each patient receives a customized dose of tisagenlecleucel that is created using immune cells called T cells harvested from his or her blood. Once the T cells have been harvested, they are genetically modified to have a new gene that encodes a protein called a chimeric antigen receptor (CAR). After the T cells are modified, they are expanded in number and then infused back into the patient. The CAR directs the infused modified T cells to CD19-positive B cell ALL cells and triggers them to attack once they get there.
The approval of tisagenlecleucel was based on results from the phase II
ELIANA clinical trial. According to the
FDA statement, 83 percent of the 63 children and young adults who were treated with tisagenlecleucel had remission within three months of receiving the CAR T-cell therapy. Previously published
data from earlier, smaller clinical trials suggest that for some patients, remission following tisagenlecleucel treatment is durable, but further follow-up is needed to determine long-term overall survival rates.
It is important to note, however, that treatment with tisagenlecleucel can cause severe adverse effects. One of the most concerning of these is cytokine-release syndrome, which is a systemic response to the activation and proliferation of the CAR T cells that causes high fever and flu-like symptoms. It can also cause life-threatening neurological events. Thus, the approval comes with a boxed warning for cytokine-release syndrome and neurological toxicities. In addition, the FDA expanded the approval of a medication called tocilizumab (Actemra) to include the treatment of CAR T cell–induced severe or life-threatening cytokine-release syndrome in patients ages 2 and older. This expanded approval was based on clinical trial data showing that 69 percent of patients treated with CAR T–cells had complete resolution of cytokine-release syndrome within two weeks following one or two doses of tocilizumab.
To further reduce risk to patients receiving tisagenlecleucel, the FDA has put in place a risk evaluation and mitigation strategy that requires that health care facilities using the new treatment be specially certified. As part of that certification, the health care facilities must have onsite, immediate access to tocilizumab and the staff involved in the prescribing, dispensing, or administering of tisagenlecleucel must be trained to recognize and manage cytokine-release syndrome and neurologic events.
Read the complete blog post.