The U.S. Food and Drug Administration issued draft guidance, Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics, regarding clinical trial design considerations to support accelerated approval applications. The accelerated approval pathway is commonly used for approval of oncology drugs in part due to the serious and life-threatening nature of cancer and because of available intermediate clinical endpoints likely to predict clinical benefit.

“The FDA’s accelerated approval program has provided patients with cancer earlier access to novel treatments that can be practice changing,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Today’s draft guidance provides recommendations to sponsors for designing clinical trials to support accelerated approval. Building quality and efficiency into the design of oncology clinical trials is a crucial component in providing maximum benefit to those living with cancer.”

The draft guidance discusses the design of clinical trials, and ways to improve the data available at the time of accelerated approval and reduce clinical uncertainty for patients by initiating postmarketing confirmatory studies in a timely manner. Specifically, the draft guidance addresses the design, conduct and analysis of data through two randomized clinical trial approaches – conducting two separate randomized controlled clinical trials or using one trial for both accelerated approval and to verify clinical benefit. The draft guidance also provides considerations for sponsors to determine the adequacy of single-arm studies to support an application.
  
For drugs granted accelerated approval, postmarketing confirmatory trials have been required to verify and describe the anticipated clinical benefit. The draft guidance discusses a potential advantage of randomized clinical trials–compared to single-arm trials–by highlighting that use of the one-trial approach, in appropriate cases, may not require separate clinical trials because longer term follow-up in the same trial could fulfill a postmarketing requirement to verify clinical benefit. Moreover, confirmatory trials that are in progress at the time of accelerated approval are more likely to result in a timely verification of clinical benefit, therefore minimizing the period of uncertainty for patients.

In a commentary in the New England Journal of Medicine in 2022External Link Disclaimer, Oncology Center of Excellence staff outlined the concepts included and expanded upon in the draft guidance. The Oncology Center of Excellence has also launched Project Confirm, as an initiative that promotes the transparency of outcomes related to accelerated approval for oncology indications and  fosters discussion and research on the accelerated approval program. The project developed a searchable database with information on the status of all oncology accelerated approvals, a model that was then adopted by FDA’s Center for Drug Evaluation and Research for all accelerated approvals.

Related Information

• Oncology Center of Excellence Guidance Documents
• Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics Guidance for Industry 
• Accelerated Approval Program
• Project Confirm

Source: FDA

The U.S. Food and Drug Administration today issued draft guidance that provides food manufacturers with recommendations on how and when to use Dietary Guidance Statements on the label of food products to ensure the label statements promote good nutrition, provide greater consistency in labeling, and assist consumers in making informed choices. This guidance is part of the FDA’s overall goal to help reduce the burden of chronic disease and advance health equity through improved nutrition. 

“Diet-related chronic diseases, are the leading causes of death and disability in the U.S. and disproportionally impact communities of color and people living in rural areas,” said FDA Commissioner Robert M. Califf, M.D. “The FDA is committed to being a part of the solution to improve the health of millions of Americans. Today’s action is another step towards helping consumers make informed choices about the foods they eat.”

Today’s eating patterns in the U.S. do not align with current federal dietary recommendations, which focus on the entirety of the diet and how foods and beverages work together to affect health. Dietary Guidance Statements are statements in food labeling which are based on key recommendations from consensus reports, such as the Dietary Guidelines for Americans, 2020-2025, that discuss how a food or food group can be a part of a nutritious dietary pattern. The statements may include symbols or pictures that convey to consumers that a food or a food group may contribute to, or help maintain, a nutritious dietary pattern. 

Examples of Dietary Guidance Statements include: “Make half your grains whole grain,” and “Eat leafy green vegetables as part of a nutritious dietary patten.” The draft guidance provides the agency’s thinking about the use of such statements, including recommendations that products contain a meaningful amount of the food, or category of foods, that is the subject of the statement, and that they also not exceed certain amounts of saturated fat, sodium and added sugars. The recommendations in the guidance can enhance consistency in the use of such statements and consumer understanding as well as facilitate industry innovation toward healthier foods. Like other labeling statements and claims, Dietary Guidance Statements act as quick signals on food packages to help consumers better understand nutrition information and make healthier food choices. 

Today’s action is part of the FDA’s overall nutrition initiatives, which include empowering consumers by providing more informative labeling and education, including tailored messages for various audiences to help consumers identify foods that can contribute to healthier diets. It is also part of the Biden-Harris Administration’s National Strategy on Hunger, Nutrition, and Health, which provides a roadmap of actions the federal government will take to end hunger and reduce diet-related diseases by 2030 – all while reducing disparities. Complementing today’s guidance and the National Strategy, the FDA issued a proposed rule in September 2022 to update the definition of “healthy” on food labels and help consumers more easily identify healthy food choices. The agency’s work also supports the Biden-Harris Administration’s White House Challenge to End Hunger and Build Healthy Communities, a nationwide call-to-action to stakeholders across all of society to make bold commitments to advance the Strategy’s goals. The 
Challenge builds on the success of the $8 billion package of private and public sector commitments that the Administration announced as part of the historic conference.

Another priority of the FDA’s nutrition efforts is to create a healthier food supply for all. In October 2021, the FDA issued final guidance for the food industry that provided voluntary, short-term sodium reduction targets for a broad range of processed, packaged and prepared foods to help reduce the amount of sodium in the U.S. food supply. 

“In addition to the Dietary Guidance Statements draft guidance, reducing sodium intake and updating the definition of “healthy” are two other examples of how the agency is showing its commitment to fostering a healthier food supply for all and empowering consumers with more informative and accessible labeling to choose healthier diets,” said Susan Mayne, Ph.D., director of the FDA’s Center for Food Safety and Applied Nutrition. “We are making great strides in our nutrition initiatives in order to improve the health and wellness of our nation.” 

The FDA remains committed to doing its part in the all-of-government approach to improving nutrition, which can have a lasting generational impact on reducing chronic diseases and advancing health equity. The agency is moving forward with additional nutrition and labeling priorities, including exploring a “front-of-pack” labeling initiative and recommendations for nutrition labeling for online grocery shopping sites. Additionally, the FDA will begin assessing further strategies to reduce added sugar consumption, which includes collaborating with others in the U.S. Department of Health and Human Services and the U.S. Department of Agriculture to hold a public meeting regarding future steps the federal government could take to reduce intake of added sugars.

Related Information

• Draft Guidance: Questions and Answers About Dietary Guidance Statements in Food Labeling: Guidance for Industry
• Constituent Update: FDA Issues Draft Guidance on Dietary Guidance Statements on Food Labels
• Press Release: FDA Proposes Updated Definition of ‘Healthy’ Claim on Food Packages to Help Improve Diet, Reduce Chronic Disease
• Press Release: To Improve Nutrition and Reduce the Burden of Disease, FDA Issues Food Industry Guidance for Voluntarily Reducing Sodium in Processed and Packaged Foods
• FDA’s Nutrition Initiatives

Source: FDA

Company Must Stop Marketing Unauthorized Products

Today, the U.S. Food and Drug Administration issued marketing denial orders (MDOs) for two menthol e-cigarette products currently marketed by R.J. Reynolds Vapor Company under the Vuse Solo brand. The currently marketed products include the Vuse Replacement Cartridge Menthol 4.8% G1 and the Vuse Replacement Cartridge Menthol 4.8% G2. The company must not market or distribute these products in the U.S. or they risk FDA enforcement action. The company may resubmit applications or submit new applications to address the deficiencies for the products that are subject to these MDOs. 

The FDA evaluates premarket tobacco product applications (PMTAs) based on a public health standard that considers the risks and benefits of the product on the population as a whole. After reviewing the company’s PMTAs, the FDA determined that the applications lacked sufficient evidence to demonstrate that permitting the marketing of the products would be appropriate for the protection of the public health, which is the applicable standard legally required by the 2009 Family Smoking Prevention and Tobacco Control Act. Specifically, evidence submitted by the applicant did not demonstrate that its menthol-flavored e-cigarettes provide an added benefit for adult smokers relative to tobacco-flavored e-cigarettes.

“The FDA is a data driven agency and science remains the cornerstone of our tobacco product regulatory activities,” said Brian King, Ph.D., M.P.H., director of the FDA’s Center for Tobacco Products. “The science has guided – and will always guide – the FDA’s decision making on premarket tobacco product applications, including today’s marketing denial orders.”   

Existing evidence, including data from the 2022 National Youth Tobacco Survey (NYTS), shows that non-tobacco-flavored e-cigarettes, including menthol-flavored e-cigarettes, have a known and substantial risk with regard to youth appeal, uptake and use. In contrast, data indicate tobacco-flavored e-cigarettes do not have the same appeal to youth and therefore do not pose the same degree of risk. Given these existing differences in youth risk, applicants need to provide robust evidence to demonstrate that using their menthol-flavored e-cigarette products are likely to promote complete switching or are likely to significantly reduce combustible cigarette use in adult smokers beyond that facilitated by tobacco-flavored e-cigarettes. NYTS data also found Vuse to be the second most common brand youth e-cigarette users reported “usually” using.

These products cannot be legally introduced into interstate commerce in the U.S. without risking FDA enforcement. In addition to ensuring that the manufacturer complies with this order, as with unauthorized products generally, the FDA intends to ensure compliance by distributors and retailers. Retailers should contact R.J. Reynolds Vapor Company with any questions about products in their inventory. 

Today’s actions are just one of many the FDA has taken to ensure any tobacco products that are marketed in the U.S. undergo science-based review and receive marketing authorizations by the agency. To date, the agency has received applications for more than 26 million deemed products and has made determinations on 99% of these applications. To date, the FDA has authorized 23 tobacco-flavored e-cigarette products and devices, which are the only e-cigarettes that currently may be lawfully sold or distributed in the U.S.; this includes the Vuse Solo e-cigarette device and two accompanying tobacco-flavored e-liquid cartridges. The FDA has also denied marketing applications for millions of products that did not meet the requirements in the law, including ten non-tobacco-flavored e-liquid cartridges under the Vuse Solo brand, Vuse Vibe Tank Menthol 3.0% and the Vuse Ciro Cartridge Menthol 1.5%. 

Related Information

• Tobacco Products Marketing Orders
• Premarket Tobacco Product Applications
• Quitting Smoking and Other Tobacco Public Health Resources
• Safety Reporting Portal for Tobacco Products | FDA