Cancer Policy Monitor-January 2020
Cancer Policy Monitor January 14, 2020
- Appropriations Update from Capitol Hill
- Hahn Confirmed as FDA Commissioner
- Congress Raises Purchasing Age of Tobacco Products to 21, but New Policy Causes Concern
- Advocate Insights and Inspiration for Transdisciplinary Innovation
- World Health Organization Deliberates on the Elimination of Cervical Cancer as a Global Public Health Problem
- “N-of-One” Study Approved, FDA Guidance Expected
- Preparing for PDUFA VII: A User Fee Primer
- FDA Oncology Center of Excellence Envisions Future
- Registration Now Open for FDA-AACR Workshop to Examine Under-representation of African Americans in Multiple Myeloma Clinical Trials
- Registration Available for FDA-AACR-IASLC Workshop to Address Tobacco Use Assessment in Oncology Therapeutic Trials
- AACR to Release Cancer Health Disparities Progress Report at March 25 Briefing on Capitol Hill
- Save the Date for the 2020 AACR/AACI Hill Day
- Oncology Approval Recap
Appropriations Update from Capitol Hill
-J. Tod Guidry, PhD
Just before leaving for the holidays, Congress passed legislation to fully fund the federal government through fiscal year (FY) 2020, narrowly avoiding a government shutdown. Included in the legislation are substantial funding increases for the National Institutes of Health (NIH) and the National Cancer Institute (NCI), as well as a nation-wide increase in the legal age to purchase tobacco products.
Congress provided a $41.7 billion budget for the National Institutes of Health (NIH), representing a $2.6 billion increase over FY 2019 levels. The National Cancer Institute (NCI) received a FY 2020 budget of $6.44 billion, a $296 million increase over FY 2019 levels.
In September 2019, the AACR coordinated the seventh annual Rally for Medical Research, in partnership with over 350 other organizations, to urge Congress to adopt an increase of at least $2.5 billion for the NIH in FY 2020. This marks the fifth straight year of an increase of at least $2 billion for NIH compared to the preceding year.
Budgets for the NIH and NCI and all other agencies and programs that receive federal funding were consolidated into two measures passed by the Senate on December 19, one day before the deadline set by the most recent continuing resolution (CR). Both packages were previously passed by the House of Representatives.
The funding measures also included an increase of $10 million overall for cancer control programs at the CDC and reauthorized the Patient Centered Outcomes Research Institute (PCORI) for 10 more years. PCORI’s authorization had expired on September 30 but had been extended through two CRs.
In addition to setting government funding levels, the legislation also increased the legal age to purchase tobacco to 21 years across the nation. This action is one of several the AACR has previously called on both Congress and the Trump administration to take to reduce the uptake of tobacco products among youth. The AACR also urges action to prohibit the manufacture and sale of flavored tobacco products that have not undergone FDA review; restrict the online sale of all tobacco products; enforce restrictions on marketing tobacco products to youth; and increase funding for prevention and cessation activities.
The AACR applauds Congress’ commitment to the health of Americans by once again providing robust federal funding for life-saving medical research and urges lawmakers to continue enacting legislation to curb youth tobacco use.
Hahn Confirmed as FDA Commissioner
-J. Tod Guidry, PhD
In a bipartisan 72-18 vote, the Senate confirmed Stephen M. Hahn, MD, as commissioner of the U.S. Food and Drug Administration (FDA) on December 12. Hahn’s confirmation follows the resignation of former commissioner Scott Gottlieb, MD, in the spring and eight months of temporary leadership by two acting commissioners.
Hahn’s extensive background in medicine and research make him well suited for his new role at the FDA. At the time of his nomination, Hahn was the chief medical executive at the University of Texas MD Anderson Cancer Center. Before taking the helm at MD Anderson in 2015, he chaired the Department of Radiation Oncology at the University of Pennsylvania School of Medicine for nine years, and prior to that he was a senior investigator at the National Cancer Institute. A member of the AACR since 1999, Hahn has served on the AACR Radiation Science and Medicine Working Group Steering Committee and the Clinical and Translational Cancer Research Scientific Review Committee. He also cochaired the FDA-AACR-ASTRO Workshop on Clinical Development of Drug-Radiotherapy Combinations in 2018.
“Dr. Hahn brings impressive qualifications to this extremely important position, including his background as a highly regarded physician and extremely effective scientific administrator,” said AACR President Elaine R. Mardis, PhD, co-executive director of the Institute for Genomic Medicine at Nationwide Children’s Hospital.
The Senate’s confirmation of Hahn provides stable leadership to an agency that has lacked a permanent commissioner since April. Norman “Ned” Sharpless, MD, director of the NCI, served as acting commissioner until November, when Assistant Secretary for the Department of Health and Human Services, Admiral Brett Giroir, MD, temporarily took up the mantle.
Hahn inherits several challenges confronting the FDA, particularly the public health crisis stemming from the explosion in youth e-cigarette use. Appearing before the Senate Committee on Health, Education, Labor, and Pensions prior to his confirmation, Hahn was pressed on whether he supports President Trump’s earlier proposal to ban most flavored e-cigarettes, a plan on which the president has recently waned. Hahn did not declare a position, though he did affirm that the epidemics of youth vaping and vaping-related illness require aggressive action.
Other issues facing Hahn include the FDA’s efforts to incorporate real-world evidence into regulatory decision-making and the president’s desire to allow the importation of prescription drugs. Hahn committed to prioritizing patients’ needs and basing regulatory decisions on sound science in his new role: “Patients need to come first, and the decisions that we make need to be guided by science and data, congruent with the law.”
Congress Raises Purchasing Age of Tobacco Products to 21, but New Policy Causes Concern
-Carmine S. Leggett, PhD
The American Association for Cancer Research (AACR) has long supported legislative efforts to raise the minimum age of tobacco product sales. On December 20, 2019, as a provision of the broader $1.4 trillion federal government funding package, President Trump signed legislation to amend the Federal Food, Drug, and Cosmetic Act, raising the purchasing age of tobacco products, including e-cigarettes, to 21. According to a 2015 report from the National Academies of Science, Engineering and Medicine, raising the minimum purchasing age of tobacco products from 18 to 21 will likely delay initiation of use and decrease the prevalence of tobacco users in the U.S. population. This new federal law is an important step in addressing the national epidemic in youth e-cigarette use. Use of e-cigarettes among U.S. youth and young adults has increased exponentially in recent years and surpassed that of adults. Of note, results from the 2019 National Youth Tobacco Survey (NYTS) conclude that over 5 million youth are using e-cigarettes, while nearly 1.6 million used the product daily. These alarming rates warrant public health concern, particularly from policymakers and the cancer advocacy community.
Such a major change in federal tobacco policy resulted from months of negotiations after two bipartisan Tobacco 21 bills were introduced in Congress. Senate Majority Leader McConnell (R-KY) and Senator Kaine (D-VA) introduced the Tobacco-Free Youth Act, while Senators Schatz (D-HI), Young (R-IN), Durbin (D-IL), and Romney (R-UT) introduced the Tobacco to 21 Act. The Tobacco to 21 Act had a companion bill in the House of Representatives introduced by Representatives DeGette (D-CO), Stewart (R-UT), Cohen (D-TN), Herrera Beutler (R-WA), Payne (D-NJ), Flores (R-TX), and Wittman (R-VA). The AACR endorsed the bills and worked closely with Senate Majority Leader McConnell’s office to ensure that the final legislation reflected our organization’s priorities. The AACR applauds the new federal law and calls on policymakers to continue to take action to reduce the well-characterized health risks associated with tobacco use.
The AACR and other public health groups have advised that while raising the tobacco sale age to 21 is critical to addressing the youth e-cigarette epidemic, it is important to add measures that prevent use of flavored tobacco products among youth and young adults. In September 2019, the Trump Administration announced its intention to remove all non-tobacco-flavored e-cigarettes from the market. However, the final policy announced on January 2, 2020 reflected a weakened compromise between public health officials and proponents of the vaping industry within the Administration. The policy indicates that the Food and Drug Administration will ban major retailers, gas stations and convenience stores from selling all mint-, fruit- and sweet-flavored vapes, but allow menthol-flavored e-cigarettes to be widely available. The announcement also allows the sale of open tank vapes commonly sold in vape shops. Further, FDA intends to prioritize enforcement of any ENDS product that is offered for sale after May 12, 2020, and for which the manufacturer has not submitted a premarket application (or after a negative action by FDA on a timely submitted application). This announcement causes public health concern because use data strongly conclude that youth are attracted to both mint and menthol products. In fact, the 2019 NYTS show that of high school students over half of e-cigarette users use mint or menthol, while the 2019 Monitoring the Future results indicate that youth who use JUUL prefer mint- and fruit-flavored e-cigarettes. Considering the appeal of these flavors, these data support predictions that youth may switch to menthol flavored e-cigarette products. The AACR will continue to engage with Congress and the Administration on tobacco product policies in an effort to reduce the incidence of disease and mortality due to tobacco use.
Advocate Insights and Inspiration for Transdisciplinary Innovation: A Post 2019 CRUK-AACR Engineering, Physical Sciences And Oncology Meeting Reflection
-Susan Samson, MA, MPH1,2 and Carole Baas, PhD3
1Breast Science Advocacy Core (BSAC), Breast Oncology Program, 2Helen Diller Family Comprehensive Cancer Center, 3Alamo Breast Cancer Foundation
On October 15-17, 2019, the Cancer Research UK-American Association for Cancer Research (CRUK-AACR) jointly sponsored the Engineering, Physical Sciences and Oncology Meeting in London. This multidisciplinary program explored how emerging technologies and novel approaches can transform our understanding of biology to optimize detection, diagnosis, and treatment. The meeting also considered gaps in knowledge as well as scientific and infrastructure barriers that impede progress. Potential frameworks for addressing challenges and moving the field forward were proposed.
As persistent advocate champions of convergent science1-4, our enthusiasm to attend this informative meeting was fueled by the conviction that pairing advocates with iconic networks of international experts in physics, engineering, structural and evolutionary biology, and mathematics would offer fresh perspectives on disease states; multidisciplinary collaboration; cancer research in the big data era; emerging technological opportunities and challenges for cancer discovery and diagnosis; as well as engineered solutions to therapeutic approaches.
Representing the advocate voice at the meeting, we eagerly embraced the challenge of providing context to the evolving field of advocacy engagement within the physical sciences and oncology and offered examples of innovative science advocate collaborative partnerships, engagement platforms, and resources that foster and support best practices across the research continuum.
The meeting’s inspiring research, captivating presentations, and celebration of multidisciplinary collaboration across networks provided reasons to be excited about emerging technologies, biophysical solutions to enhance detection, and the future of novel diagnostic therapeutic technologies, as well as unconventional science communication styles.
Notably, presenting our poster, “Conceptual Model of Transdisciplinary Science-Advocacy Collaboration for the Physical Sciences and Oncology: Case Study Focusing on Breast Density, Biomarker Discovery, and Emerging Therapeutics”5 provided transformative opportunities for advancing the science, promoting bi-directional mentor matching, as well as making advocacy mainstream.
Spotlighting the research of Drs. Jason Northey and Irene Acerbi, postdoctoral fellows in Dr. Valerie Weaver’s laboratory at UCSF, the poster brought into sharp focus a better understanding of how the organization of cell-to-cell contacts, tissue architecture, tissue microenvironments, and mechanical properties may ultimately improve strategies and best practices for breast cancer prevention, care, and control.
So how does advocacy meet innovation as an evolving paradigm in convergent science?
On the cusp of an evolving era of breast density research, we highlighted how advocates have a pivotal role to play in mechanobiology settings as cultural brokers, visionaries, and agents of change. Forwarding the imperatives think boldly and creatively, question the status quo, consciously break down silos and identify challenges that impede progress, advocates worked toward a common set of goals with researchers and clinicians in determining that elevated extracellular matrix (ECM) stiffness may promote breast cancer risk by establishing low microRNA-203 and high ZNF217 expression as well as high progesterone/RANKL signaling to drive oncogene associated processes such as mammary epithelial stem/progenitor cell expansion and proliferation. This knowledge could then enable the identification of patients at higher risk for breast cancer who should receive added surveillance or prophylactic clinical intervention.
Applying National Cancer Institute Office of Advocacy Relations (NCI OAR), University of California, San Francisco Breast Science Advocacy Core (UCSF BSAC), and NCI-Physical Sciences Oncology Network (PS-ON ) Patient Advocacy Working Group goals for strategic innovation, collaborative execution, and ethical codes of conduct, we also highlighted how UCSF and NCI PS-ON researchers and advocates co-developed guiding conceptual frameworks based on organizational foundations, systems readiness, leadership commitment to change, and transdisciplinary levers to promote shared governance, bidirectional collaboration, advocacy inclusion, and the prioritization of research addressing questions of importance to patients. Together, we spurred unique training/mentoring exchanges; identified strategic priorities; and co-created educational strategies, including training curriculum toolkits, instructional materials, and videos5.
Furthermore, networking with attendees at the meeting, we referenced the contributions of creative advocates from different PS-ON Regional Centers and elsewhere in advancing robust professional development and training, (Cornell) creative education and outreach activities (H.Lee Moffit; Houston Methodist Research Institute; and novel science entrepreneurial and communication programs, ARTIDiS; Northwestern University; University of Minnesota).
Appreciating AACR’s track record in promoting new horizons of advocate engagement across the physical sciences and oncology, we were at the forefront at the meeting spotlighting advances in advocacy engagement. We were thrilled to use the opportunity to network, translate research findings, and converge innovative communication and entrepreneurial approaches in physical sciences and oncology.
Importantly, the hidden gem within CRUK-AACR’s decision to imbue advocate perspectives and priorities at this convergent science meeting was the recognition, at a conceptual policy level, that as the anchor and facilitator to Scientist Survivor partnerships, it must strive not only to enable engagement but also to increase transdisciplinary innovation velocity and bi-directional communication.
Yet, although we have never witnessed a time of greater promise for advancing advocacy engagement to help bring convergent science out from the shadows of the laboratory, we realize that further culture and process change is needed to address scientific challenges regarding reductionism, status quo thinking, heterogeneity, biomarker discovery, evolution and the microenvironment. Moreover, structural/organizational challenges regarding training, increased time, resource/funding constraints, metrics development, and tokenistic inclusion also must be addressed.
To help counter barriers to the revolutionary vision of what convergent science could become, we believe that advocate contributions in forwarding trailblazing frontiers within physical sciences and oncology should be formally embedded as a standard of practice by government, academic, and professional organizations. Progress against cancer requires the relentless perseverance and visionary minds of scientists and advocates working together towards driving the technologies behind scientific discoveries into the clinic.
As invested patient centric partners, we need to further develop and implement sustainable frameworks for balancing, improving, and acting upon meaningful advocate recommendations. And importantly, we must all be willing to defend advocacy credibility and equitable inclusion to help ensure that we can look forward to a bright future working together.
This work was supported by grants from the Department of Defense (DOD) W81XWH-13-1-0216; the National Institutes of Health NIH/NCI R01 CA138818-01A1and R01CA222508-01; the UCSF Helen Diller Family Comprehensive Cancer Center (Give Breast Cancer the Boot); a Susan G. Komen Breast Cancer Foundation Fellowship PDF12230246; an AACR Basic Cancer Research Postdoctoral Fellowship and an AACR-Janssen Fellowship in Cancer Interception Research.
Attendance at the meeting was supported by the UCSF Helen Diller Family Comprehensive Cancer support grant (P30CA82103) and funding provided by Andrei Goga and Zena Werb.
Both authors are graduates and members of AACR’s Scientist↔Survivor Program.
We acknowledge the contribution of all poster co-authors: Jason Northey, Irene Acerbi, Susie Brain, Zena Werb, Laura Van’t Veer, and Valerie M. Weaver.
Special thanks to Jason Northey, Nasatrian Zahir, Laura Van’t Veer, Carrie Treadwell, Anna Barker, Marija Plodinec, Christian Jaeggi, David Walsey, and Allan Samson for their editorial input.
- Samson, S., et al., Advocacy spurs innovation: promoting synergy between physical and biomedical sciences. EPJ Nonlinear Biomedical Physics. 2013.
- Samson, S., et al., New Horizons in Advocacy Engaged Physical Sciences and Oncology Research. Cell Trends in Cancer. 2018.
- Samson, S., et al., Regional strategies for expanding the evolving continuum of Physical Sciences-Oncology Network (PS-ON) research advocacy experiences. AACR Annual meeting 2018, Chicago, IL. Poster Abstract #4767.
- Fresques T., et al., Breast Tissue Biology Expands the Possibilities for Prevention of Age-Related Breast Cancers. Frontiers in Cell and Developmental Biology. 2019.
- Samson S., et. al., Conceptual Model of Transdisciplinary Science – Advocacy Collaboration for Physical Sciences-Oncology in Breast Density, Biomarker Discovery, and Emerging Therapeutics. Cancer Research UK-AACR Joint Conference: Engineering and Physical Sciences in Oncology, Leonardo Royal Hotel Tower Bridge, London, England, October 15 – 17, 2019.
World Health Organization Deliberates on the Elimination of Cervical Cancer as a Global Public Health Problem
-Audrey Jackson, PhD
At its upcoming meeting from February 3-8, 2020, the Executive Board of the World Health Organization (WHO) will review a draft global strategy to accelerate the elimination of cervical cancer as a global public health problem. The global strategy was requested by the United States and other WHO member states at the January 2019 meeting of the WHO Executive Board, and it has been developed by the WHO Secretariat in consultation with member states and other stakeholders. The strategy is based on country implementation and scale-up of interventions that have been proven to be effective against cervical cancer:
- vaccination against the human papillomavirus (HPV),
- screening for and treatment of pre-cancerous lesions,
- early detection and treatment of invasive cancers, and
- palliative care.
In 2018, an estimated 570,000 women developed cervical cancer globally, and 311,000 died, according to the International Agency for Research on Cancer. In the absence of a coordinated global public health response, the number of annual cases is projected to rise to 700,000 by 2030, with a projected 400,000 deaths annually. In May 2018, WHO Director-General Dr. Tedros Adhanom Ghebreyesus issued a global call to action toward the elimination of cervical cancer as a public health problem. It is important to note that elimination as a public health problem falls along a continuum of infectious disease control, ranging from control to eradication, that was put forth by the WHO in 1998.
- Control: Reduction in incidence, prevalence, morbidity, or mortality to a locally defined level
- Elimination as a public health problem: Reduction in incidence, prevalence, morbidity, or mortality to commonly agreed targets that will improve public health
- Elimination of infection/disease: Incidence of infection or disease reduced to zero in a defined geographical area, such as a country
- Eradication: Worldwide incidence of infection reduced permanently to zero
WHO has defined the threshold for the elimination of cervical cancer as a public health problem as an incidence of less than four per 100,000 women. According to global experts, cervical cancer incidence cannot be reduced to zero with current interventions, but elimination as a public health problem is achievable in every country within this century. To make progress towards elimination, the draft strategy sets the following targets for 2030:
- 90% of girls fully vaccinated with HPV vaccine by 15 years of age;
- 70% of women screened twice by 35 and 45 years of age;
- 90% of women identified with pre-cancerous lesions or invasive cancers treated
The AACR has adopted the elimination of cervical cancer and other HPV-related cancers as a domestic and global policy priority. While HPV is the causative agent for six cancers, cervical cancer is currently the most feasible elimination target because of the availability of screening for pre-cancerous lesions. In response to the WHO call to action, in June 2018 the AACR joined with all the National Cancer Institute (NCI)-designated cancer centers and several other organizations to endorse the goal of eliminating HPV-related cancers, beginning with cervical cancer. In June 2019, the AACR, the former Biden Cancer Initiative, and the Moffitt Cancer Center co-hosted a congressional briefing, “Let’s End HPV-Related Cancers” in partnership with the American Cancer Society Cancer Action Network (ACS CAN), American Society of Clinical Oncology (ASCO), Association of American Cancer Institutes (AACI), Prevent Cancer Foundation, St. Jude Children’s Research Hospital, and the Union for International Cancer Control (UICC). Speakers presented on the latest interventions and a path towards elimination. AACR leaders Dr. Anna Giuliano and Dr. Gilbert Omenn, Chair of the AACR Health Policy Subcommittee, published an op-ed in STAT News outlining recommendations for policymakers. To further spur action, the AACR and collaborators issued a Call to Action urging accelerated U.S. action. The AACR will continue to work with national and global policymakers to advance toward the elimination of cervical cancer as a public health problem.
Following discussion by the WHO Executive Board in February, the draft global strategy to accelerate the elimination of cervical cancer as a global public health problem will be presented for adoption by all member states at the World Health Assembly in May 2020. Once adopted, implementation of the strategy will require leadership by country governments and multi-sectoral collaboration. Scaling up HPV vaccine coverage will require an increase in the current global supply of vaccines and improved vaccine affordability. Evidence-based communication, social mobilization, and vaccine delivery strategies will be critical to overcome vaccine hesitancy and to support vaccine acceptance and uptake. Screening and treatment of pre-cancerous lesions particularly in low- and middle-income countries (LMICs) will require the evaluation and implementation of novel diagnostic approaches, such as HPV testing with self-sampling, and novel treatment approaches, such as simple hand-held devices for thermal ablation. It will be important to integrate screening and treatment services into primary health care systems and build health care worker capacity. In LMICs, diagnosis and treatment of invasive cancers will require expanded capacity for pathology, surgery, radiotherapy, chemotherapy, and palliative care. Training, partnerships, workforce development, and the establishment of regional centers are various strategies to build such capacity. There will be many challenges to achieving the WHO 2030 targets for HPV vaccination, screening, and treatment of pre-cancerous and invasive cancer cases. But if the challenges are met, millions of cases of cervical cancer will be averted and subsequently millions of lives saved.
“N-of-One”Study Approved, FDA Guidance Expected
-Brittny Davis Lynn, PhD, MPH, and Tod Guidry, PhD
Brittny Davis Lynn, PhD, MPH, is a Research Fellow in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Her research focuses on breast cancer etiology in minority populations.
Tod Guidry, PhD, is the inaugural AACR Science Policy Fellow.
Single-patient studies face numerous regulatory challenges on which the U.S. Food and Drug Administration (FDA) is expected to soon issue guidance, and such “N-of-One” treatments could even be designed to treat cancers with unique molecular signatures. Mila Makovec, a now 8-year-old girl with a typically fatal brain disease, experienced substantial therapeutic benefit when treated with an anti-sense oligonucleotide (ASO), dubbed milasen, that was designed especially for her. Milasen targets the unique genetic mutation responsible for her condition. The drug’s developer received FDA approval to treat Mila after demonstrating milasen’s ability to correct the mutation in cells cultured from her skin.
When feasible, large randomized controlled trials involving hundreds of patients are often used to demonstrate clinical benefit of a new drug for FDA approval. However, very small patient populations in rare diseases make it challenging to confirm a treatment’s safety and efficacy, especially in “N-of-One” cases such as for milasen.
Janet Woodcock, MD, and Peter Marks, MD, PhD, Directors for the Center for Drug and Evaluation Research and the Center for Biologics and Evaluation Research at the FDA, respectively, highlighted the challenges the FDA faces when regulating “N-of-One” therapies in an editorial published in the New England Journal of Medicine. Woodcock and Marks encouraged investigators to consider what evidence is needed before administering a drug to a patient, including the dosage, treatment regimen, and a minimum assurance of safety.
Investigators must also balance conducting a thorough investigation with a timely one, given the potential rapidly progressive nature of the targeted disease. Thorough preclinical studies may also face financial constraints, given that most costs are paid out of pocket by the patients and their families. Lauren Black, senior scientific consultant at a contract research organization that develops “N-of-One” therapies, stated that the developers work to minimize preclinical studies while still satisfying FDA expectations to manage expense.
“We don’t want to sidestep anything necessary for a thorough safety characterization… but we cull the research down to the bare minimum and make sure the FDA is on board with that amount,” she said.
Once the “N-of-One” therapy is administered, the investigators must then determine whether it benefits the patient. Quantifiable measures of the patient’s disease status and objective goals for symptom improvement must be identified in advance and set to ensure an accurate measure of efficacy. Woodcock and Marks highlight that determining treatment efficacy in single-patient studies may be especially difficult when hopeful patients and their families are so closely involved in the treatment development, as they may perceive disease improvement or stabilization not quantifiable by investigators.
Overall, standards for preclinical evaluation of a drug in a single-patient study need to reflect the severity of the disease as well as the feasibility and safety of the treatment. In Makovec’s case, for example, the drug developers state that the treatment approach they employed should only be considered for life-threatening neurological diseases with no available alternative treatment. Woodcock and Marks recognize the challenge in deciding how the urgency of the patient’s situation and the ultimate number of other beneficiaries of the treatment should influence the decision-making process.
The regulatory challenges associated with “N-of-One” studies could soon be faced by developers of cancer drugs, as therapies to treat unique molecular signatures underlying different cancers are developed. As cancer therapies become more precisely targeted, clinical trial sample sizes become increasingly smaller, approaching and potentially reaching an n of one. Larotrectinib and entrectinib, tissue-agnostic therapies used to treat solid tumors in adult and pediatric patients, were granted accelerated approval based on very small efficacy trials completed with just 55 and 54 patients, respectively. Given the regulatory challenges involved, the FDA is carefully considering how to evaluate such individualized therapies and is expected to issue draft guidance on their regulation in the near future.
Preparing for PDUFA VII: A User Fee Primer
Beth Oates is a fourth year PhD candidate in the department of Microbiology, Immunology and Molecular Genetics at the University of Kentucky, College of Medicine, Lexington, Kentucky. Her research is focused on understanding bacterial competition and community interactions and the resulting effects on pathogenicity. Beth is also interested in the influence of disease on science and public health policy.
The Prescription Drug User Fee Act (PDUFA) was first passed in 1992 by the United States Congress in order to allow the US Food and Drug Administration (FDA) to collect fees from drug developers to fund new drug approval processes. PDUFA sprang from dissatisfaction among consumers, industry, and the FDA over the length of time it was taking before new drugs could be approved.
Prior to PDUFA, the FDA estimated that a delay of just one month in a drug review process cost companies about $10 million. The backlog of drugs awaiting FDA review was, in part, due to understaffing and insufficient appropriation of funds from Congress. This backlog led to outrage during the 1980s AIDs epidemic when treatment options were extremely limited. AIDs activists put pressure on the government and drug companies to increase drug approvals, creating an environment that led to the first PDUFA. Once Congress, FDA, and industry agreed on setting target completion times for reviews and that these application fees would supplement not supplant federal appropriations, PDUFA was approved and passed by Congress.
To continue collecting user fees, the FDA is required to meet certain performance benchmarks primarily related to the speed of certain activities within the New Drug Application (NDA) review process. According to PDUFA, the deadline for FDA review of new drugs is typically 10 months after the 60-day filing date. However, if a drug is selected for priority review, the FDA is allowed six months after the 60-day filing date. In 2002, the United States Government Accountability Office (GAO) reported that PDUFA allowed the number of personnel assigned to review applications to increase by 77 percent after the first eight years of the Act. During this period, the approval time for new drugs dropped from an average of 27 months to 14 months. Since PDUFA was enacted in 1992, the FDA has approved over 1,000 new drugs.
Increased efficiency in drug approvals due to PDUFA-related changes has increased patient access to new medications by allowing pharmaceutical companies to launch their drugs in the United States first. Additionally, increased communication between FDA and the pharmaceutical industry means that the application process has become more streamlined and efficient. Prior to 1992, the FDA would send back dozens of drug approval applications due to missing information or inadequate preparation. David Kessler, MD, the commissioner of the FDA during the implementation of PDUFA, reported that in 1993 thirty-four new applications were sent back to the drug manufacturers but by 1996 only six were refused.
Updating and Reauthorizing PDUFA
PDUFA is updated, reviewed, and approved by Congress every five years. Each reauthorization focuses on various components of the drug development and review processes. With each reauthorization, there is a new opportunity to rectify any issues that have arisen since the last revision, allowing the bill to adapt to the changing biomedical landscape. Previous reauthorizations addressed areas such as review management practices, regulatory science initiatives, and product safety. This adaptability makes PDUFA a versatile and effective way to improve drug review processes. The most recent PDUFA reauthorization, PDUFA VI, was for fiscal years 2018-2022. While the next reauthorization of PDUFA by Congress, PDUFA VII, won’t technically be needed until 2022, conversations between the FDA, drug industry representatives, patient and consumer advocates, health care professionals, and other public stakeholders are already underway.
PDUFA VII is one of three related pieces of legislation to undergo reauthorization in 2022. The Biosimilar User Fee Act (BsUFA) and Generic Drug User Fee Amendments (GDUFA), similar acts that cover user fees specifically for biosimilars and generic drugs respectively, are also due for review and reauthorization. Building off the successes of PDUFA, BsuFA and GDUFA employed similar user fee models to further encourage efficient and timely drug development and review.
Early discussions among stakeholders suggest the focus for PDUFA VII will be to increase the use of benefit/risk assessment frameworks and patient centricity through patient-focused drug development programs. The FDA’s incorporation of real-world evidence and patient-reported outcomes to help increase efficiency in the drug approval process are also expected to be included in these discussions. In addition, the agency predicts an increase of drug approval applications in novel areas such as cell-based therapies and biomarker-driven therapies for a variety of diseases, including cancer. This will require an increase in staffing at the FDA to fulfil the deadline requirements put forth by PDUFA and ensure the expertise needed to effectively regulate these novel areas of development is in place. Even with an increase of staff at the agency, developing and prioritizing new operational processes to improve the use of staff time and expertise will be necessary if key patient populations are to receive treatments more efficiently.
Although the upcoming reauthorization of PDUFA is critical, it is equally important to continue robust funding for the FDA as a part of the annual federal budget. Combined with the user fee program, strong federal funding will ensure that the agency is well-equipped to meet its mission to protect public health.
FDA Oncology Center of Excellence Envisions Future
Since 2017, the Oncology Center of Excellence has worked to develop innovative programs to advance drug development and regulation for cancer therapies. In February, they will be sharing an update on their progress and a vision for the future of the center.
Registration Now Open for FDA-AACR Workshop to Examine Under-representation of African Americans in Multiple Myeloma Clinical Trials
The American Association for Cancer Research (AACR) is partnering with the U.S. Food and Drug Administration (FDA) to present the FDA-AACR Workshop to Examine Under-representation of African Americans in Multiple Myeloma Clinical Trials on February 13, 2020, in Washington, DC. The workshop is cochaired by:
- Kenneth C. Anderson, MD, FAACR, Program Director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics and Chief, Division of Hematologic Neoplasia, Dana-Farber Cancer Institute; Chair, AACR Regulatory Science and Policy Subcommittee
- ‘Lola A. Fashoyin-Aje, MD, MPH, Acting Deputy Director, Division of Oncology 3, Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
- Nicole J. Gormley, MD, Acting Director, Division of Hematologic Malignancies 1, Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
- Paul G. Kluetz, MD, Deputy Director, Oncology Center of Excellence, U.S. Food and Drug Administration
RegistrationAvailable for FDA-AACR-IASLC Workshop to Address Tobacco Use Assessment in Oncology Therapeutic Trials
The American Association for Cancer Research (AACR) is partnering with the U.S. Food and Drug Administration (FDA) and International Association for the Study of Lung Cancer (IASLC) with support from the American Society of Clinical Oncology (ASCO) to present the FDA-AACR-IASLC Workshop to Address the Criticality of Tobacco Use Assessment in Oncology Therapeutic Trials on February 28, 2020 at the U.S. FDA’s White Oak campus in Silver Spring, MD. This workshop is co-chaired by:
- Roy S. Herbst, MD, PhD, Ensign Professor of Medicine, Associate Director for Translational Research, Yale Cancer Center
- Michael E. Menefee, MD, Oncologist, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
- Matthew Steliga, MD, Surgical Oncologist, Winthrop P. Rockefeller Cancer Institute
AACR to Release Cancer Health Disparities Progress Report at March 25 Briefing on Capitol Hill
Cancer research is fueling a record number of approvals for anticancer therapeutics. Overall cancer incidence and death rates are declining, and the number of cancer survivors has reached a record high. Despite this progress, cancer still has a disproportionate impact on disadvantaged and minority groups.
AACR has long recognized the need to address cancer health disparities through cancer research programs and initiatives. AACR’s Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved marked its 12th year of convening the research community. Developed in collaboration with AACR’s Minorities in Cancer Research Council and Constituency Group, the conference strives to bring research on health disparities from the bench to the community. A critical tool to combat cancer health disparities is community engagement. AACR added its Scientist↔Survivor Program to the Conference to support partnerships with patient advocates from underrepresented communities.
In 2018, AACR formed a Cancer Health Disparities Task Force and hosted a Think Tank, comprised of leading experts in cancer disparities, to chart the future direction of AACR’s cancer health disparities programs. One of the products of the Task Force has been the development of a Cancer Health Disparities Progress Report which will be shared with members of Congress and their staff through a Congressional Briefing and Hill Day on March 25, 2020.
We welcome all of you to join AACR on Capitol Hill to advocate for research and policies that address cancer health disparities. As a community of patient advocates, cancer survivors, researchers, and physician-scientists, we have a compelling and important story to tell.
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Save the Date for the 2020 AACR/AACI Hill Day
The AACR and the Association of American Cancer Institutes (AACI) invite you to Capitol Hill Wednesday, May 13, 2020 for our joint Hill Day. This event will bring cancer center directors, researchers, physician-scientists, cancer survivors and other advocates to Washington, DC to build support for a strong federal investment in cancer research. Stay tuned for more information and registration details.
Oncology Approval Recap
In December, the U.S. Food and Drug Administration granted two accelerated approvals and three expanded indications to oncology therapies:
- Atezolizumab was approved in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.
- Enzalutamide was approved for patients with metastatic castration-sensitive prostate cancer (mCSPC).
- Enfortumab vedotin-ejfv was granted accelerated approval for adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.
- Fam-trastuzumab deruxtecan-nxki was granted accelerated approval for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
- Olaparib was approved for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
Read more about the approval of olapirib, enfortumab vedotin-ejfv, and other new approvals on the AACR Cancer Research Catalyst. To learn more about the approval of other cancer therapies, you can find more information on the FDA’s website, and an AACR journal, Clinical Cancer Research, regularly publishes FDA approval summaries.