from Biocentury
9:38 PM EDT | MAY 12, 2017 | BIOCENTURY | POLITICS, POLICY & LAW
INNOVATION MANDATE
SCOTT GOTTLIEB’S BIPARTISAN MANDATE FOR INNOVATION
BY STEVE USDIN, WASHINGTON EDITOR
Scott Gottlieb was sworn in as FDA commissioner with a clear, bipartisan mandate to continue and accelerate regulatory innovations that speed the transformation of scientific progress into medical products and to intensify the participation of patients in regulatory decisions.
Gottlieb will start with a large measure of goodwill among career FDA staff and members of Congress who heaved massive sighs of relief when he was selected for the position over candidates who had denigrated the agency’s civil servants and ridiculed the basic premises of modern medical product regulation.
Even Democratic senators who did not vote for him decided not to stall confirmation because they want Gottlieb to help push reauthorization of medical product user fees onto President Donald Trump’s desk before FDA has to start notifying thousands of reviewers that they may be laid off.
Gottlieb arrived on FDA’s White Oak campus on May 12, a day after the Senate Health, Education, Labor and Pensions (HELP) Committee passed medical product user fee reauthorization legislation. The HELP vote set the stage for a vote by the full Senate.
Gottlieb will start with a large measure of goodwill among career FDA staff and members of Congress.
The House Energy & Commerce Committee’s health subcommittee is likely to discuss user fee reauthorization legislation on May 17, and the full committee could pass it the following week. This would put both the House and Senate on track to pass the bills well before the summer break starts at the end of July.
Although there is bipartisan agreement to get user fees reauthorized quickly, in the current political environment, surprises or controversies that would delay or derail legislation are always possible.
The user fee legislation, combined with the 21st Century Cures Act that was enacted in December, will give FDA a great deal of discretion about how it advances regulatory innovation. The two laws also will provide Gottlieb new tools to recruit and retain staff, and even more importantly, put Congress on record as supporting FDA’s use of its power to proactively advance medical product development.
The premise of the 996-page Cures Act is that increased government investment in and new ways of thinking about biomedical innovation and regulation can produce more “cures.” It promotes patient-focused drug regulation, along with pushing FDA to qualify more drug development tools including biomarkers and surrogate endpoints, and to facilitate the use of novel clinical trial designs.
The PDUFA VI agreement commits FDA to advance its engagement with patients from town hall-style meetings to the development of rigorous tools for the collection and assessment of patient preferences.
The new PDUFA deal also would provide resources for and commit FDA to moving forward on model-informed drug development, biomarker qualification and novel clinical trial designs.
Gottlieb is likely to layer new innovation initiatives on top of the measures mandated in PDUFA and 21st Century Cures.
GETTING USER FEES DONE
To get rolling on PDUFA VI and new user fee agreements for biosimilars, generic drugs and medical devices, one of Gottlieb’s most pressing tasks will be ushering the FDA Reauthorization Act of 2017 (S. 934) and a similar House bill through Congress and onto the president’s desk.
HELP Chairman Lamar Alexander (R-Tenn.) has cut a deal with Democrats on his committee that should make the Senate process relatively smooth.
Alexander secured cooperation from Democrats to quickly move the user fee bill out of the committee by agreeing to their demands to hold at least one, and possibly as many as three, hearings on prescription drug costs. Based on this commitment, HELP Democrats withdrew a number of contentious amendments and agreed to limited discussion before the full committee passed S. 934 in a 21-2 vote.
The deal both speeds the user fee reauthorization to the floor, and provides opportunities to separate drug price control proposals from FDA legislation.
The two laws put Congress on record as supporting FDA’s use of its power to proactively advance medical product development.
The committee approved an amendment sponsored by Sens. Susan Collins (R-Maine) and Al Franken (D-Minn.) that would fast-track ANDAs if there were three or fewer generic versions of a product on the market. The goals of the amendment are consistent with policies Gottlieb advocated prior to his nomination and in his confirmation hearing.
So far, Congress has backed away from entangling FDA and Gottlieb in controversies over commercial-scale prescription drug importation. Gottlieb has opposed importation in the past and declined to endorse it during his confirmation hearing, despite Trump’s public statements supporting importation.
The HELP Committee voted 13-10 against an amendment offered by Sen. Bernie Sanders (I-Vt.) to allow importation from Canada and possibly other countries.
Sanders is expected to introduce the amendment again when the full Senate considers S. 934, and the vote will almost certainly be close.
In January the Senate defeated a non-binding amendment that expressed support for importation in a 46-52 vote. After the vote, several of the Democrats who voted against importation said they would favor it in future votes, and President Trump has expressed strong support for importation.
Alexander submitted but did not request a vote on a poison pill amendment that would effectively neuter importation by making any attempt to bring drugs into the U.S. contingent on declarations by the HHS secretary that doing so would not create health or safety risks, increase exposure to counterfeit drugs or exacerbate the opioid crisis.
If the amendment is added to S. 934 it would strengthen current law enacted during the Clinton administration, which allows importation only if the HHS secretary certifies it can be done safely and would produce meaningful financial savings.
By piling on the requirements about counterfeits and opioids, Alexander’s proposal would make it even more difficult for any HHS secretary to honestly certify that importation met all of the legal criteria.
Congress is likely to continue to resist efforts to hurt biopharma companies by attaching price controls to user fee legislation, or to help them by including new market exclusivities or other incentives.
ADDRESSING ACCESS?
HELP green-lighted an amendment sponsored by Sens. Orrin Hatch (R-Utah), Michael Bennet (D-Colo.), Richard Burr (R-N.C.), and Bob Casey (D-Pa.) that addresses some of the concerns expressed by patient advocates who are seeking easier access to unapproved therapies.
The amendment would require FDA to create guidance about expanding clinical trial inclusion criteria to more accurately reflect populations who will receive drugs. The amendment specifically mentions expanding trials to include children, and patients with co-morbid conditions.
FDA and medical societies already have been pressuring drug developers to expand entry criteria for clinical studies so patients can access investigational drugs without resorting to compassionate use.
The Hatch amendment also would change the law to allow sponsors to publicize the availability of unapproved drugs through compassionate use, or expanded access, 15 days after receiving breakthrough therapy, Fast Track or regenerative medicine advanced therapy (RMAT) designations. Under the current law, companies cannot communicate about expanded access until products are in Phase II or III trials.
If enacted, the amendment could reduce pressure on Congress to pass right-to-try (RTT) legislation that Trump and Vice President Mike Pence have endorsed. For FDA, the most problematic part of right-to-try legislation that has been introduced in both houses of Congress is language prohibiting the agency from considering safety signals that emerge from use of unapproved drugs outside of a clinical trial.
In response to a question about RTT posed to him as part of the confirmation process, Gottlieb committed to policies that would “appropriately balance individual patients’ needs for access to investigational therapies while recognizing the importance of maintaining a rigorous clinical trial paradigm for testing investigational products and demonstrating safety and efficacy.”
TARGETING PEDIATRIC CANCER
Lobbyists will be working overtime to persuade the Senate leadership to slip additional provisions into S. 934 before the full Senate votes, and those who fail will be pressing senators to introduce amendments.
Some of the most intense lobbying and negotiations will involve the fate of an amendment Bennet withdrew at last week’s hearing.
The amendment was based on the Research to Accelerate Cures and Equity (RACE) for Children Act (S. 456, H.R. 1231), which seeks to modify the Pediatric Research Equity Act (PREA) to stimulate pediatric cancer trials.
PREA requires sponsors to conduct pediatric trials of drugs that are being developed for adults if the condition the drug is intended to treat occurs in children. It hasn’t led to more pediatric cancer trials, because under conventional definitions based on the site where tumors occur, children and adults rarely get the same kinds of cancer.
In addition, there is an exemption from PREA for Orphan drugs, and in recent years about 90% of cancer drugs have had Orphan status.
The RACE Act would modify PREA to make it apply to pediatric cancers that are driven by the same molecular or genetic targets as an adult cancer. It also would waive the Orphan exemption for cancer drugs.
Bennet said at the May 11 hearing that FDA agrees PREA should be updated to make it applicable to pediatric cancer. He secured a commitment from Alexander to have language reflecting FDA’s views inserted into S. 934 before it is brought to the Senate floor.
Biopharma lobbyists, pediatric cancer advocates and FDA are negotiating modifications of the RACE Act with Bennet. According to congressional staff, the final legislation is likely to make PREA pediatric study requirements apply to Orphan cancer drugs “for an indication for a pediatric cancer or adult cancer if such drug or biological product is intended for the treatment of an adult cancer and is determined by scientific evidence to be directed at a molecular target” likely to be relevant to a pediatric cancer.
FDA would be required to develop and publish a list of primary molecular targets for pediatric cancers after consulting with the pediatric oncology subcommittee of the Oncologic Drugs Advisory Committee and convening a public meeting.
ONGOING REGULATORY INNOVATIONS
New regulatory innovation policies Gottlieb rolls out will likely complement those spelled out in the 21st Century Cures Act and contained in PDUFA VI.
Under Cures, FDA must develop a plan by June 11 for the creation of guidance documents on how sponsors can collect patient experience data and integrate it into drug development. The agency will then have a year to release a draft of at least one of these guidance documents.
Cures also shines a spotlight on patient data by requiring that FDA include in drug approval announcements “a brief statement regarding the patient experience data and related information, if any, submitted and reviewed.”
The PDUFA VI agreement commits FDA to release draft guidance in FY19 “describing processes and methodological approaches to development of holistic sets of impacts that are most important to patients.”
The guidance will include FDA’s thinking about determining the factors that are most important to patients “in terms of burden of disease, burden of treatment, and other critical aspects.” It also will “address how patient input can inform drug development and review processes, and, as appropriate, regulatory decision making.”
Cures also requires the agency to develop plans for the integration of real-world evidence to support approvals of new indications of approved drugs.
Both Cures and PDUFA VI commit FDA to devote more resources to the review of biomarkers and surrogate endpoints and to the development and assessment of novel clinical trial designs. The user fee agreement commits FDA to start a pilot project in FY18 for “highly innovative trial designs for which analytically derived properties (e.g., Type I error) may not be feasible, and simulations are necessary to determine trial operating characteristics.”
FDA’s ability to implement regulatory science provisions of previous user fees has been undermined by its long-running inability to hire and recruit staff. PDUFA VI seeks to fix the agency’s human resources problems by requiring that it adopt practices common in the private sector, such as contracting with headhunters, and by setting hiring goals.
The 21st Century Cures Act complements these provisions by giving FDA the ability to offer salaries that are competitive with private sector pay.
COMPANIES AND INSTITUTIONS MENTIONED
U.S. Food and Drug Administration (FDA), Silver Spring, Md.
REFERENCES
Usdin, S. “Balancing act.” BioCentury (2017)
Usdin, S. “Beyond right to try.” BioCentury (2017)
Usdin, S. “Christmas in July.” BioCentury (2017)
