Former FDA Commissioner Scott Gottlieb Will Offer Insights at Upcoming Oncology Conferences

OncologyLive, Vol. 20/No. 20, Volume 20, Issue 20

In an interview with OncologyLive®, Scott Gottlieb, MD, shared his insights on developments in the oncology arena.

Scott Gottlieb, MD

When Scott Gottlieb, MD, stepped down from his post as FDA commissioner in April 2019, he had earned praise and respect for his willingness to take on important issues, such as opioid regulation1 and the marketing of tobacco products to youths2 (Timeline1-10).

In oncology, Gottlieb, himself a Hodgkin lymphoma survivor, oversaw the introduction of FDA guidance on patient warnings about the cancer risks inherent in dense breast tissue and took steps to spur the development of biosimilars.3,4 The FDA also pushed to streamline the drug approval process by establishing the Oncology Center of Excellence, which unified the actions of FDA product centers for expedited reviews of drugs, biologics, and devices.

A robust pace of new oncology agent and medical device approvals was maintained during Gottlieb’s tenure, and the FDA began developing a framework for 2 incipient fields of medicine: the regulation of regenerative medicine5 and artificial intelligence (AI) in medical devices.6

The first chimeric antigen receptor (CAR) T-cell therapies were approved during Gottlieb’s eventful term: tisagenlecleucel (Kymriah) for relapsed/refractory (RR) B-cell acute lymphoblastic leukemia and RR large B-cell lymphomas, and axicabtagene ciloleucel (axi-cel; Yescarta) for adult patients with certain types of RR large B-cell lymphoma.7

Although Gottlieb’s tenure at the FDA lasted less than 2 years,8,9 he remains a thought leader in the field of medicine, particularly oncology. Today, he is a resident fellow at the American Enterprise Institute, a public policy think tank; a partner at New Enterprise Associates, a venture capital firm; and a member of the board of directors of Pfizer, the pharmaceutical giant. His prior experience in medicine includes serving as a clinical assistant professor and hospitalist physician at the New York University School of Medicine in New York, New York.

He will deliver the keynote addresses at 2 upcoming conferences hosted by Physicians’ Education Resource, LLC (PER®): the 37th Annual CFS®: Innovative Cancer Therapy for Tomorrow®, scheduled for November 6 to 8 in New York, New York, and the 37th Annual Miami Breast Cancer Conference®, set for March 5 to 8, 2020, in Florida.

In an interview with OncologyLive®, Gottlieb shared his insights on developments in the oncology arena. Reflecting on his experience and the future of oncology, he said that physicians and researchers must incorporate innovation into every aspect of a patient’s cancer journey. “This isn’t only at diagnosis,” Gottlieb said. “It affects patient onboarding, staffing, cutting-edge therapeutic options, and much more. The trick is learning how to implement all these advances into daily practice.”

Timeline. Highlights of Scott Gottlieb's Tenure at FDA

He said the entire field of cancer care is being transformed through new technology. Not just new therapeutics, but new diagnostic tools are also profoundly changing the way doctors practice oncology.

CAR T Price Structure Concerns

However, innovation often comes with high prices, at least in the short term. Gottlieb said the advancement of CAR T and other cellular therapies has been hampered by the price of developing and administering these novel treatments. Axi-cel hit the market at a hefty $373,000 per infusion, while tisagenlecleucel was launched at $475,000 per dose, price tags that do not include all ancillary costs of care.11,12

In a national coverage decision issued in August, the Centers for Medicare & Medicaid Services indicated that CAR T-cell therapy would be covered under certain conditions, along with related costs of care.13 The decision also increases the amount institutions are reimbursed for the product cost of CAR T-cell therapy from 50% to 65%, according to the American Society of Hematology.14 However, how private payers manage the costs associated with CAR T-cell therapy and other high-cost medicines still needs to be addressed. Several payment models have been discussed.

“We’re at a real inflection point when it comes to things like CAR T and cell-based medicine,” Gottlieb said. “We need to come up with a reimbursement scheme that’s carefully tailored to these technologies. If we don’t get this right, it could become an impediment to future innovation and certainly future investment.”

Gottlieb said such has been the case with the radiopharmaceuticals ibritumomab tiuxetan (Zevalin) and tositumomab with iodine I 131 tositumomab (Bexxar). The competing agents were launched in the early 2000s and touted as the first of a new class of drugs; however, payment issues complicated access to these agents.

Ibritumomab tiuxetan is a CD20-directed monoclonal antibody linked with the radioactive substance yttrium-90 and indicated for RR low-grade or follicular (FL) B-cell non-Hodgkin lymphoma (NHL).15 Tositumomab, a radiotherapeutic that was pulled from the market in 2012, was indicated for patients with CD20-positive, RR, low-grade, follicular, or transformed NHL.16

Gottlieb said the radiopharmaceuticals offered advantages, but the payment structure meant that some prescribers took a loss with each dose.

“Eventually Medicare changed its payment rules, but it was too late,” he said. “Doctors stopped using them, hospitals didn’t build the facilities for delivering them, and we saw investment pull away from the field of radiopharmaceuticals. It hasn’t been until recently that we’ve seen investment now come back into radiopharmaceuticals.”

He said that a similar situation could arise with CAR T-cell therapies because, in many cases, payment is not keeping up with cost. As with the radiopharmaceuticals, some hospitals delivering CAR T-cell therapies are doing so at a loss, and that could result in investment dollars flowing elsewhere.

“I’m optimistic we’ll get this right, but right now, a lot of institutions that are delivering CAR T are, in some cases, delivering it at an economic loss,” he said. “You’re seeing physicians steer patients to clinical trials because hospitals are losing money on the administration of CAR T. That’s not sustainable over the long run.”

He advocates an outcomes-based model in which payment is scaled according to the patient’s response to the product. Gottlieb said such a model would ultimately provide accountability and ensure that if these products remain on the market, they are improving outcomes. “Those things have been talked about, but it’s going to require Medicare to come up with sort of a wholesale different model than how it traditionally pays for products,” he said.

A Role for AI, Real-World Data

Gottlieb said that it has been exciting to witness the advent of targeted treatments that can provide more benefit with less of the toxicity associated with chemotherapy. However, some of the most exciting developments are occurring in diagnostics. Data processing tools can evaluate real-world evidence to find important correlations that are undetectable through casual observation

“Now we can apply things like artificial intelligence to look at patients’ own genomic data to [search] for insights that previously we wouldn’t have seen,” he said. “That’s really going to change the practice of medicine.”

During Gottlieb’s tenure at the FDA, the agency inaugurated a regulatory program to ensure that medical devices that use AI algorithms are safe and effective. The FDA expects to see more of these devices incorporate AI algorithms to improve their performance.

Early products in this category employed “locked” algorithms that didn’t learn from new data, and the industry is moving toward “adaptive” algorithms. For example, they could potentially become better over time at identifying breast cancer lesions on mammograms, Gottlieb speculated in an April FDA release on AI regulation.6 The FDA initiated regulatory architecture that would allow for modifications to algorithms to be made from real-world learning and adaptation.

“Oncologists are very good at innovating their medical practices and adopting new tools and adopting new innovations, but I think the cycle of innovation that we’re going to see, particularly on the diagnostic side, is really exciting,” Gottlieb said.

Gottlieb said that real-world data have roles to play in regulatory actions. The FDA will make use of real-world data and data gleaned from electronic medical records to conduct post-market safety surveillance. “Traditionally, the FDA has relied on payer claims data as part of its sentinel system,” he said. “You’re going to see much more of a reliance on real-world data gleaned from electronic medical records.”

Drug manufacturers, he said, will use real-world data to improve information on drug labels and support new drug indications. Gottlieb added that there will always be a role for prospectively enrolled clinical trials, particularly for the market entry of a product. However, he said manufacturers will rely more and more on real-world evidence, especially for rarer conditions where it is more difficult to accrue patients for clinical trials.

Efforts to Promote Biosimilars

During Gottlieb’s term, the market for biosimilars continued to evolve, but not smoothly. Gottlieb noted “headwinds” and a disappoint-ing pace of progress. Overall, the FDA has approved 23 biosimilars to branded biologics, including 9 therapeutic and 5 supportive care products for oncology indications. However, patent battles have stalled biosimilars from reaching the market, and some drug developers have downscaled their biosimilar programs because of the uncertainty surrounding their market access.

Gottlieb noted that the development of a biosimilar is not a “trivial” task for companies, with estimated costs range from $100 million to $300 million. “A lot of those costs are not necessarily [associated with] clinical trials, but the cost of actually developing the biosimilar,” Gottlieb said. “I think that there are ways to continue to make the development process more efficient, in terms of the kind of clinical information that is required through the regulatory process.”

In December 2018, when Gottlieb announced measures to stimulate biosimilar development, he said, “This is a dynamic market, and we’ll continue to address potential barriers to competition as they emerge, including in partnership with colleagues at the Federal Trade Commission.”4

There is room to improve the efficiency and process of biosimilar approval, but Gottlieb believes that the value proposition and opportunities for biosimilars rest elsewhere. “I think where we are going to have the most ability to move the needle when it comes to biosimilar adoption is more on the commercial side and physician adoption [through] educating doctors about biosimilars and looking at some of the structures of the market that create impediments to biosimilars launching effectively,” he said.

References

  1. FDA requests removal of Opana ER for risks related to abuse [press release]. The FDA; November 8, 2017. www.fda.gov/news-events/press-announcements/fda-requests-removal-opana-er-risks-related-abuse. Accessed August 19, 2019.
  2. FDA takes new steps to address epidemic of youth e-cigarette use, including a historic action against more than 1,300 retailers and 5 major manufacturers for their roles perpetuating youth access [press release]. The FDA; September 12, 2018. www.fda.gov/news-events/press-announcements/fda-takes-new-steps-address-epidemic-youth-e-cigarette-use-including-historic-action-against-more. Accessed 19, 2019.
  3. FDA advances landmark policy changes to modernize mammography services and improve their quality [press release]. The FDA; March 27, 2019. www.fda.gov/news-events/press-announcements/fda-advances-landmark-policy-changes-modernize-mammography-services-and-improve-their-quality. Accessed August 19, 2019.
  4. Statement from FDA Commissioner Scott Gottlieb, M.D., on new actions advancing the agency’s biosimilars policy on framework [press release]. Silver Spring, MD: FDA; December 11, 2018. www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-actions-advancing-agencys-biosimilars-policy. September 12, 2019.
  5. FDA announces comprehensive regenerative medicine policy framework [press release]. The FDA; November 16, 2017. www.fda.gov/news-events/press-announcements/fda-announces-comprehensive-regenerative-medicine-policy-framework. Accessed August 19, 2019.
  6. Statement from FDA Commissioner Scott Gottlieb, M.D. on steps toward a new, tailored review framework for artificial intelligence-based medical devices [press release]. The FDA; April 2, 2019. www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-steps-toward-new-tailored-review-framework-artificial. Accessed August 19, 2019.
  7. Hematology/oncology (cancer) approvals & safety notifications. FDA website. fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications. Updated August 8, 2019. Accessed September 12, 2019.
  8. Thomas K. Senate confirms Scott Gottlieb to head F.D.A. The New York Times. www.nytimes.com/2017/05/09/health/scott-gottlieb-senate-fda-commissioner.html. Published May 9, 2017. Accessed August 19, 2019.
  9. Kaplan S, Hoffman J. F.D.A. commissioner Scott Gottlieb, who fought teenage vaping, resigns. The New York Times. www.nytimes.com/2019/03/05/health/scott-gottlieb-resigns-fda.html. Published March 5, 2019. Accessed September 13, 2019.
  10. FDA warns homeopathic firms for putting patients at risk with significant violations of manufacturing quality standards [press release]. The FDA; April 1, 2019. www.fda.gov/news-events/press-announcements/fda-warns-homeopathic-firms-putting-patients-risk-significant-violations-manufacturing-quality. Accessed August 19, 2019.
  11. Clarke T, Berkrot B. FDA approves Gilead cancer gene therapy; price set at $373,000. Reuters Health News website. reuters.com/ article/us-gilead-sciences-fda/fda-approves-gilead-cancer-genetherapy-price-set-at-373000-idUSKBN1CN35H. Published October 18, 2017. Accessed September 12, 2019.
  12. Kleutghen P, Mitchell D, Kesselheim AS, Najafzadeh M, Sarpatwari A. Drugs don’t work if people can’t afford them: the high price of tisagenlecleucel. Health Affairs website. www.healthaffairs.org/do/10.1377/hblog20180205.292531/full/. Published February 8, 2018. Accessed September 12, 2019.
  13. Trump administration makes CAR T-cell cancer therapy available to Medicare beneficiaries nationwide [press release]. Baltimore, MD: US Centers for Medicare and Medicaid Services; August 7, 2019. www.cms.gov/newsroom/press-releases/trump-administration-makes-car-t-cell-cancer-therapy-available-medicare-beneficiaries-nationwide. Accessed September 12, 2019.
  14. Statement from ASH president Roy Silverstein, MD, on medicare reimbursement for CAR T-cell therapy [press release]. Washington, DC: American Society of Hematology; August 6, 2019. Accessed September 12, 2019.
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  16. GlaxoSmithKline LLC; withdrawal of approval of the indication for treatment of patients with relapsed or refractory, low grade, follicular, or transformed CD20 positive non-Hodgkin's lymphoma who have not received prior rituximab; BEXXAR. Federal Register. www.federalregister.gov/documents/2013/10/23/2013-24840/glaxosmithkline-llc-withdrawal-of-approval-of-the-indication-for-treatment-of-patients-with-relapsed. October 23, 2013. Accessed September 12, 2019.
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