The White House moonshot to accelerate progress in cancer research directs FDA to consolidate its oncology portfolio.
However, oncology insiders say the manner in which the presidential initiative will be implemented could make the difference between political balderdash and genuine improvement in FDA regulation of cancer therapies.
The entire controversy boils down to the interpretation of one word: Virtual.
According to a fact sheet that accompanies President Barack Obama’s memorandum on the moonshot, “the FDA will develop a virtual Oncology Center of Excellence to leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics, and devices.” (The Cancer Letter, )
This directive comes with $75 million in new mandatory funds for FDA in fiscal 2017.
For the past three months, agency insiders and outside observers have been pondering the meaning of the word “virtual.”
Oncology professional societies and several advocacy groups want the FDA cancer center to be organized to include the agency’s entire cancer portfolio: drugs, biologics, immunotherapies, cellular therapies, diagnostics and other devices.
Ideally, the new center would be placed under the same physical—as opposed to virtual—roof and under the same chain of command, proponents say (The Cancer Letter, ). This plan has the support of the American Society of Clinical Oncology, the American Association for Cancer Research, Friends of Cancer Research and other groups.
This level of consolidation appears to be running into internal opposition at FDA, particularly in units that stand to lose authority, staff and budget in a reorganization.
One example is the Center for Devices and Radiological Health, which has a broad purview over diagnostics, which are an essential component of precision oncology. Would some cancer diagnostics work be moved to another administrative unit?
Another entity that stands to lose clout is the Center for Biologics Evaluation and Research, which regulates cellular and immunotherapy, using its own set of procedures and relying on the Oncologic Drugs Advisory Committee and its own advisory committee. CBER appears to apply standards that differ from those of the Office of Hematology and Oncology Drug Products, located within the Center for Drug Evaluation and Research (The Cancer Letter, ).
What does the White House mean by virtual, and how does FDA intend to approach implementation of the moonshot?
Speaking at a recent FDA-sponsored workshop by a group called Accelerating Anticancer Agent Development and Validation, Gregory Simon, executive director of the White House Cancer Moonshot Task Force, said that virtual is “not a bad word.” Moving desks at FDA may not be necessary to achieve the moonshot’s goals, Simon said.
FDA officials said the structure and staffing for the virtual cancer center will be established in fiscal 2017.
“Specifically, in FY 2017 (October 1, 2016 to September 30, 2017), the FDA will establish the structure and staffing for the Oncology Center of Excellence, create the required virtual regulatory environment and coordinate with the NIH National Cancer Institute,” FDA officials said to The Cancer Letter.
Oncology advocates and professional societies say a virtual reorganization is not enough. Desks and the chain of command should shift as well. Moreover, FDA leadership needs to present a detailed blueprint of its plans for the cancer center much sooner than the next fiscal year, these groups say.
“This is about patient need. We need to hear from the FDA on what they think the structure of an Oncology Center of Excellence should be,” said Ellen Sigal, founder and chair of Friends of Cancer Research, a group playing a central role in creating the legislative language for the cancer center. “We look forward to working with FDA leadership, with input from all stakeholders, on creating meaningful integration through the centers of excellence.
“We have to integrate that in a way that is meaningful, so we can have diseases where oncologists really make these decisions,” Sigal said to The Cancer Letter. “Of course, the skillsets in all these divisions are really important, and I wouldn’t for one moment suggest that the skillset in CDRH or in CBER isn’t important, but they have to be integrated in a way with disease experts who are working together and where decisions are made.”
The existing centers already work collaboratively, agency officials said in response to questions from The Cancer Letter about whether FDA oncologists in the drug and biologics divisions are being consulted in plans for the center of excellence.
“Currently, the reviews for cancer products exist in separate FDA ‘centers’—CDER, CBER, and CDRH,” FDA said in a statement May 5. “However, there are already examples of these centers working collaboratively across review divisions, such as for drugs or biologics (CDER/CBER) that are approved with a companion diagnostic (CDRH).
“We also have an Office of Combination Products with the distinct and important role of serving as a focal point for combination product issues for agency reviewers and industry. This office helps provide guidance and clarity on the differing regulations that may come up with products that combine a drug/biologic and device, and helps ensure consistency with premarket review and postmarket regulation.”
The full text of FDA’s response appears below.
Legislation to create the FDA Intercenter Institutes is underway in Congress.
The FDA and NIH Workforce Authorities Modernization Act was introduced in the Senate March 17, and a similar version will be introduced in the House next week.
Aimed at improving coordination of FDA activities, the bill would establish one or more institutes according to major disease areas no later than one year after the measure is enacted.
This means that it will fall on another administration and another Congress to implement this directive.
Moonshot Chief Executive: It’s Up to FDA
More time should be spent on creating collaborations than moving offices, said Simon, formerly a senior vice president for patient engagement at Pfizer and CEO of Poliwogg, a financial services company investing in the life sciences, prior to joining the White House Cancer Moonshot Task Force.
“First off, we agree with the need for this, and I know FDA does, too,” Simon said, responding to a question from The Cancer Letter. “And the FDA has come a long, long way in oncology in my 30 years in Washington, and 20 years since I was last in the government.
“By ‘virtual,’ I think if we spend a lot of time when we try to physically move things around and we try to put people in contiguous offices and go through all the official stuff, when what we really want is an obligation for them to work together from the beginning in a joint way, regardless of whether it’s a device or biological or small molecule. So to me, virtual is not a bad word, it means that there’s a common obligation to work together, so we’re not going to spend a whole lot of time banging the office and relabeling things.”
Simon said that any internal disputes should be settled by the agency within the agency, without external interference.
“Now, there is support for this in both sides of Congress, I know the leadership supports this, I know that the patient community supports this,” Simon said. “I’m not going to prejudge exactly how they set it up, since I’ve been doing this [for] six weeks, and before I really wasn’t thinking about the FDA’s Oncology Center of Excellence to tell you the truth, I was thinking more about how we’re going to help fund companies in the Valley of Death.
“But I think that with the leadership we have right now at the FDA with [Commissioner] Robert Califf and Richard Pazdur [director of the Office of Hematology and Oncology Products], that any management issues don’t need to be dictated from outside, but can be managed from the inside. The moment you take control outside of the office, you lose control, and it becomes much harder to change anything. I guess what I’m saying is I’m holding off judgment about how specific the legislation has to be for it to be successful, but I’m sure I’m going to be hearing more about it.”
The text of Simon’s remarks at the AAADV workshop appears here.
ASCO, AACR Call for Full Integration
Nancy Goodman, executive director and founder of Kids v Cancer, said that a virtual center would fall short of scientific and patient need.
“I don’t know what ‘virtual’ means. Is that going to mean something?” Goodman said to The Cancer Letter. “Are we going to be able to actually build a separate unit with a budget and lines of responsibility and a bottom line? Is this going to be a real change? Or are we just going to put lipstick on it?
“I think this is a tipping point moment in the history of oncology, drug development and the FDA. It’s critically important that we get a center of excellence that actually means something,” said Goodman, who successfully advocated for the creation of priority review vouchers to incentivize development of drugs for rare pediatric diseases. “That means that there will be reporting right up to the top, that it has its own budget, that it has everything you need. It will be really shameful if we missed this opportunity and made it virtual.”
Earlier last month, at a meeting of the Alliance for a Stronger FDA, Califf said he plans to create the cancer center, according to the Pink Sheet, a pharmaceutical industry publication.
“The only thing I’ll say is that it’s not going to be purely virtual,” Califf said April 19. “The rest of it we’re working on. The big deal for the FDA here is a lot of public pressure to create a center of excellence in oncology, and we’re going to do that whether it’s part of legislation or not.”
A “fully integrated” cancer center is the way to go, said Richard Schilsky, chief medical officer of the American Society of Clinical Oncology.
“ASCO supports the plan to establish an FDA Oncology Center of Excellence because it is in the best interests of cancer patients,” Schilsky said to The Cancer Letter. “We also recognize that this is a large-scale agency reorganization that requires deliberate thought and planning by the FDA in how to best organize the staff, resources and lines of authority so that the new center fully achieves its goals of bringing safe and effective oncology products to market more efficiently. ASCO stands ready to work with the FDA to achieve the vision of the new center.
“As the number of oncology products continues to grow and diagnostic tests become a more important aspect of selecting the right treatment for the right patient, a fully integrated oncology center will improve regulatory efficiency and create a larger community of scientists and clinicians at the FDA deeply understand cancer biology and treatment. The FDA has done a tremendous job regulating oncology products and this reorganization will only improve on what is already a high level of excellence.”
Patients, FDA physician-scientists, modern science, and industry need an actual cancer center, not a virtual one, said Jon Retzlaff, managing director of the Office of Science Policy and Government Affairs at the American Association for Cancer Research.
“We are extremely pleased that Commissioner Califf has publicly stated that the FDA plans to establish a center of excellence in oncology, which is in our view a key part of Vice President Biden’s ‘Moonshot” initiative,” Retzlaff said to The Cancer Letter.
“We believe that the innovation that has occurred as a result of Dr. Pazdur’s leadership, as well as his entire team’s commitment to cancer patients within the OHOP, would both be magnified and strengthened through the establishment of an actual FDA Center of Excellence in Oncology. This is exactly the kind of new and strategic idea and approach that Vice President Biden is asking federal agencies to undertake and for the broader cancer advocacy community to support.
“Establishing an FDA Center of Excellence in Oncology would allow for a more disease-specific review approach to cancer therapies, and would bring FDA staff from all of the important areas of the cancer drug development process together and under one roof to ensure the rapid and timely approval of safe and effective treatments for cancer patients.
“For example, the physician-scientists at the FDA who are continuing to treat cancer patients while also analyzing and reviewing cancer drug applications, would work directly with those who have expertise in understanding how biologics, such as vaccines and gene-therapy, are evaluated and approved for patients, as well as with those who have proficiency in the area of diagnostics, and specifically those who understand the importance of reliable and effective diagnostics to accelerating personalized and precision medicine for cancer patients.
“The importance of this center is underscored by the significant increase in the number targeted therapies approved for cancer patients that rely on a diagnostic tool. In fact, some of the most exciting scientific advances of our time, genomics, proteomics and other large scale ‘omics’ approaches and technologies, are propelling the development of novel, rapid, sensitive, less invasive and more accurate molecular diagnostic tests, which in turn are enabling physicians to make more informed treatment decisions by tailoring cancer treatments based on each cancer patient’s unique molecular profile.
“An independent FDA Center of Excellence in Oncology that includes expertise from these particular areas, along with a corresponding management reporting structure and clear and concrete authorities, would fuel the progress we are seeing today in preventing, detecting, and treating cancer. In fact, this new kind of management structure at the FDA would likely be a model to be replicated across many other disease areas.
“Therefore, we strongly support the FDA Center of Excellence in Oncology, which will enable the FDA to respond even better and in a much more coordinated way to the needs of cancer patients, the interests and goals of cancer drug and test developers and manufacturers, and the rapidly changing and ever more complex scientific environment, such as what we are seeing in the areas of companion diagnostics and next-generation sequencing tests.”
The text of FDA’s statement follows:
The FDA is honored and excited to be an integral part of the National Cancer Moonshot initiative being led by the Vice President. Supporting the development and ensuring the timely review of innovative cancer therapies and diagnostics is a priority for the agency across centers for drugs, biologics and devices.
We have seen an increase in development of innovative cancer drugs in a variety of disease types, marked by the highest number of new drugs approved in 2015 in recent history. Currently, the reviews for cancer products exist in separate FDA “centers” – the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Center for Devices and Radiological Health (CDRH).
However, there are already examples of these centers working collaboratively across review divisions, such as for drugs or biologics (CDER/CBER) that are approved with a companion diagnostic (CDRH). We also have an Office of Combination Products with the distinct and important role of serving as a focal point for combination product issues for agency reviewers and industry. This office helps provide guidance and clarity on the differing regulations that may come up with products that combine a drug/biologic and device, and helps ensure consistency with premarket review and postmarket regulation.
The Cancer Moonshot initiative takes this collaborative work a step further by calling for the creation of a virtual Oncology Center of Excellence that will leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics, and devices (including diagnostics). This Center of Excellence will help expedite the development of oncology-related medical products and support an integrated approach in:
• evaluating products for the prevention, screening, diagnosis, and treatment of cancer;
• reviewing and overseeing the life cycle process for oncology-related products;
• supporting the continued development of companion diagnostic tests, and the use of combinations of drugs, biologics and devices to treat cancer; and
• developing and promoting the use of methods created through the science of precision medicine.
Planning meetings have already begun internally at the FDA for the Oncology Center of Excellence involving the Commissioner, the Associate Deputy Commissioner for the Office of Medical Products and Tobacco, along with directors of CDER, CBER and CDRH, and the FDA plans to hold listening sessions to gain input from health care professional and patient advocacy groups, as well as industry, to inform our approach.
Specifically, in FY 2017 (October 1, 2016 to September 30, 2017), the FDA will establish the structure and staffing for the Oncology Center of Excellence, create the required virtual regulatory environment and coordinate with the NIH National Cancer Institute (NCI).
While the details of the specific framework of this virtual Oncology Center of Excellence are still in the process of being developed, the FDA is actively and expediently moving forward in this important work and will share more information when possible. The FDA looks forward to working across FDA centers, the federal government and the private sector to tackle this devastating disease that touches so many American families.