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Pink Sheet – New Acting US FDA Commissioner Shares Agency's Clinical Trial Reform Message

Pink Sheet – New Acting US FDA Commissioner Shares Agency's Clinical Trial Reform Message

Executive Summary

Norman Sharpless, director of the National Cancer Institute, will become acting FDA commissioner when Scott Gottlieb departs.


The US FDA’s incoming acting commissioner shares an enthusiasm for clinical trial system reform that should mesh well with the message many senior agency officials have been pushing for years.


National Cancer Institute Director Norman Sharpless will become acting FDA Commissioner upon Scott Gottlieb’s departure next month. A physician and researcher, Sharpless specializes in leukemia and has studied the role of stem cells in cancer and aging. He has been NCI director since October 2017.


Sharpless immediately sought to calm fears that he planned substantial changes at FDA. He tweeted shortly after the announcement that “rest assured that our shared goals for patients and the public’s health will translate into my duties.”


In a message announcing Sharpless’ appointment, Gottlieb also said he “shares our mission and I know he will be embraced warmly” by the staff.

Ned Sharpless

Gottlieb wrote he already is well known to many FDA employees and “plays on a weekly basketball team with some of our medical review staff.”


“Under his skilled leadership, I’m confident the transition will be seamless and the FDA will continue to secure its consumer protection role and advance policies to promote innovation and safety for families,” Gottlieb wrote.


At NCI, Deputy Director Doug Lowy has been named acting director.

Sharpless Pushed NCI On Trial Reform

Sharpless is a proponent of increasing clinical trial efficiency, including by eliminating unnecessary exclusion criteria and encouraging wider trial access. In a 2018 interview with the American Association For Cancer Research, Sharpless said he wanted to prioritize trials that avoid diluting the participant pool and designs that will find ineffective treatments faster.


Sharpless co-authored a viewpoint article on modernizing clinical trials that appeared in the Feb. 5 issue of the Journal of the American Medical Association. He discussed NCI efforts to right-size clinical trials, such as by forgoing traditional control arm interventions and instead using “synthetic controls created with data from previous trials” when a highly active agent is tested. Sharpless also wrote that NCI is exploring pragmatic trials conducted in clinical practice settings and through “augmented annotation and aggregation of new and existing trials data to answer relevant clinical questions without additional enrollment.”


Sharpless said in the article that NCI is positioning its clinical trial portfolio to “compliment, rather than compete with efforts from industry,” given that industry now is the majority funder of cancer trials.

“Trials sponsored by the NCI that complement those supported by industry, can, for example, focus on low-prevalence cancers for which there is limited commercial incentive to sponsor clinical investigations, such as pediatric cancers, uncommon cancers, rare subtypes of more common tumors, and special patient populations,” he wrote.


Sharpless’ interest in the subject will be welcome at FDA, especially by Center for Drug Evaluation and Research Director Janet Woodcock, who along with Gottlieb has argued for many of the same reforms.


Woodcock has called for an end to the trial system’s use of digital paper and adoption of a more modern system (Also see “Reliance On ‘Digitized Paper’ Is Slowing Drug Development – US FDA’s Woodcock” – Pink Sheet, 14 Nov, 2018.), as well as greater use of master protocols and basket trials. (Also see “Master Protocols Are Both Welcome And Inevitable – US FDA’s Woodcock” – Pink Sheet, 6 Jul, 2017.)


Gottlieb also has said that contract research organizations must end their manual processes and embrace advanced data collection techniques. (Also see “Gottlieb Takes Aim At CROs’ ‘Outdated Processes’ In Push For Clinical Trial Digitization ” – Pink Sheet, 26 Nov, 2018.)


FDA also has pushed drug sponsors to avoid unnecessary exclusions when designing clinical trials. (Also see “FDA’s Clinical Trial Inclusion Policy Sold As Mild And Gentle” – Pink Sheet, 19 Feb, 2014.)


The timing did not seem intentional, but FDA on March 12 also released a suit of guidance documents addressing cancer clinical trial eligibility requirements, including for pediatric, HIV and other patients. The guidances are intended to encourage broader eligibility criteria and increase trial participation.


In addition, as part of its clinical trial reform efforts, FDA has advocated for increased use of real-world evidence and patient input. The agency is working on ways to systematically collect real-world data and helping develop new clinical outcome assessments. (Also see “US FDA Targets Migraine, Schizophrenia And Opioid Sparing Drugs For Clinical Outcome Assessment Development” – Pink Sheet, 25 Feb, 2019.)

Is A Nomination For Permanent Position Upcoming?

Sharpless would appear to have the inside track to becoming the permanent FDA commissioner, although there is no indication yet that President Trump will nominate him.


Indeed, it would seem odd for the White House to ask Sharpless to leave a prominent position in the government to only run FDA temporarily. If Trump desired a truly caretaker leader for the agency, he may have allowed a member of FDA’s career staff to become the acting commissioner, as its staff policy allows. (Also see “Gottlieb Wants His US FDA Team To Stay Together After He Departs” – Pink Sheet, 6 Mar, 2019.)


Sharpless also is following the same path as Commissioner Andrew von Eschenbach, who ran the agency from 2006 to 2009.


After four years as NCI director, von Eschenbach was named acting FDA Commissioner in September 2005. He was confirmed by the Senate as the permanent commissioner in December 2006.


Sharpless’ appointment means that FDA’s top two leaders are outsiders. Sharpless spent much of his career in academia, while Principal Deputy Commissioner Amy Abernethy, who also was rumored for the acting commissioner position, joined the agency less than a month ago (Feb. 19), after having worked in industry. (Also see “Commissioner Succession Plan? Abernethy As Gottlieb’s Number Two Offers One Option” – Pink Sheet, 17 Dec, 2018.)

Drug Pricing, Other Questions May Emerge

Should he be nominated to become the permanent commissioner, Sharpless may run into questions about industry ties and drug pricing, just like his recent predecessors.


Sharpless holds several patents, including some that appear related to drug treatments. Those may give Senators an opening to question him on the cost of medicines, as well as various patent reform proposals, during a confirmation hearing.


Congress has often debated whether NIH should invoke its “March-In” authority for products developed using NIH-licensed patents to control prices, though the Obama administration never showed much interest, and neither has Trump. (Also see “NIH Director Collins Stays On: Continuity For ‘Moonshot’ – And Barrier To ‘March In’” – Pink Sheet, 24 Jan, 2017.)


Lowering drug prices remains a top priority for the administration as well as FDA. Sharpless will inherit ongoing policies promoting increased competition and an end to brand company gaming of the patent system to prevent generic entry.


HHS Secretary Alex Azar already has said that FDA’s drug pricing effort will bridge the commissioner transition. Asked during a March 12 House hearing on the fiscal year 2020 budget whether the agency will continue its focus on generic drug approvals, Azar said “without [Gottlieb], his agenda is my agenda.”


The NCI director is selected by the president but not confirmed by the Senate, so if Sharpless were nominated to head FDA, he would face a fair bit of new scrutiny, including about any potential industry ties. The issue is not new when it comes to FDA commissioners, however. Gottlieb faced it (Also see “Gottlieb’s Confirmation: Will Industry Ties Remain A Big Deal After The Hearing?” – Pink Sheet, 3 Apr, 2017.), as did his predecessor, Robert Califf, but neither saw their nominations threatened because of it. (Also see “Califf’s Confirmation Fall-Out: Should Sponsors Worry About Research Contracts?” – Pink Sheet, 23 Nov, 2015.)

Stakeholders Applaud The Pick

The Friends of Cancer Research applauded the announcement. Founder and Chair Ellen Sigal said in a statement “we have no doubt that Dr. Sharpless will continue to navigate and direct the FDA in a manner that best benefits patients.”


FOCR President and CEO Jeff Allen said in an interview that Sharpless’ clinical research background bodes well for many of FDA’s initiatives, including those pertaining to data science and real-world evidence.


“He has certainly shown in his career that he is an innovative and rigorous thinker and I think that will translate well to the challenges he will have as FDA commissioner,” Allen said.


Ladd Wiley, executive director of the Alliance for a Stronger FDA, said in a statement that Sharpless’ varied background in academia and government and as an inventor and innovator with industry experience make him “an exceptional choice” for acting FDA Commissioner.


The Pharmaceutical Research and Manufacturers of America also said in a statement that its members are committed to working with Sharpless, but also called for a permanent commissioner to be confirmed in the near future.


A spokesperson for the Biotechnology Innovation Organization also said that FDA will be well-served by Sharpless’ leadership during the transition period.…