The Food and Drug Administration is one of America's most closely scrutinized agencies, tasked as it is with guaranteeing the safety of both food and medicine. The political winds have demanded the FDA not erect too many barriers to the approval of new drugs, particularly those treating orphan diseases and terminal illnesses, and the agency's response has been impressive.
But can it continue to deliver, while preventing therapies of more dubious value from reaching market? And can it do so while being asked to implement new initiatives like the White House's drug importation plans? And what mark will new Commissioner Stephen Hahn make on the agency?
Here are five key trends to watch at the FDA as 2020 unfolds:
The FDA's main drug review office approved 48 new drugs in 2019, and at least seven were well before the agency's deadline date as required under the Prescription Drug User Fee Act. Vertex Pharmaceuticals' triple pill Trikafta, for example, got a green light for marketing a remarkable five months early. All of the novel drugs reviewed by the agency met their PDUFA deadlines.
Twenty-nine of the drugs went through one or more of the agency's four expedited review pathways, but even then the seven early approvals beat those accelerated timelines. It's clear the FDA has grown noticeably faster in review, especially for medicines the agency believes represent a significant advance for patient care.
However, the regulator needs to be conscious that speed cannot come at the expense of careful consideration of safety risks. It would only take one safety scandal on the scale of Vioxx — Merck & Co.'s blockbuster pain pill, recalled after being linked to an increased risk of heart attack — for the FDA to put the brakes on rapid drug review.
FDA has approved two gene therapies and CAR-T cell therapies, so it now has templates for how to review advanced medical products. This year could see review of gene therapies such as Biomarin Pharmaceuticals' hemophilia treatment valrox and Sarepta Therapeutics' muscular dystrophy drug, as well as Bristol-Myers Squibb's CAR-T liso-cel.
And if the agency's own forecasts are true, 10 to 20 cell and gene therapies will be submitted annually by 2025. The FDA says it has been beefing up its review staff to meet those projections.
At some point, however, there may be an inflection point that tests the readiness of the agency's scientific and review staff. The data manipulation scandal surrounding Novartis' Zolgensma, which the agency has not yet ruled on, demonstrates how the agency needs to be alert to minute details of gene therapy submissions.
The FDA usually stays away from drug pricing issues, lacking statutory authority to regulate. And as the FDA is a science-driven agency, the federal expertise on reimbursement issues lies primarily with its sister agency, the Centers for Medicare and Medicaid Services.
However, political pressure has been strong enough that even the FDA's resources have been tapped to target pricing issues. Former FDA chief Scott Gottlieb touted the record pace of generic approvals as one way of keeping drug prices in check, and the agency won't want to let up on this in 2020, especially given the support from both political parties and President Donald Trump.
Likewise, speeding biosimilars to market will be a priority, and the FDA will be eager to review more, even if the launch is often dictated by complex legal wrangling.
But 2020 will bring new responsibilities to the FDA, too. The reimportation plan finalized by the Trump White House in December will add new burdens in terms of monitoring compliance and the safety of the drug supply chain as new products flow in from Canada and overseas. That is, of course, unless that plan is stopped by legal action by drugmakers or logistical challenges. Moreover, as recently as former commissioner Scott Gottlieb, the FDA's posture was to oppose reimportation, so overcoming staff inertia may be a challenge.
Right to try
It is now the law that patients with life-threatening conditions can have access to experimental drugs outside the formal route of clinical trials or the FDA's expanded access program. The risk of unproven medicines harming or killing patients will require the agency to balance the law's requirements that it remain mostly hands off against its role as the nation's guardian of drug safety.
The potential for some drugmakers to begin charging for entry into right-to-try programs should encourage the FDA to become a more forceful advocate for its expanded access program, which, while it may require more paperwork, would make experimental treatments available for free.
As it confronts all these issues, the agency is in the midst of leadership transition. Steve Hahn took over in December after a year that saw Scott Gottlieb resign and two acting commissioners, Ned Sharpless and Brett Giroir, arrive as caretakers. As a permanent commissioner with a presidential appointment, Hahn should be in place at least until Jan. 20, 2021, which will give much-needed stability to the agency.
Unlike his immediate predecessors, who were drawn from the federal bureaucracy, Hahn comes from the world of academic medicine. However, past experience at the National Cancer Institute should at least prepare him for the challenges of working in the federal government.
Among his immediate issues will be implementing the reimportation plan, announced the day he was sworn in as commissioner.
In addition, the agency will very soon be preparing for reauthorization of PDUFA for the fiscal years in 2023 and after, and will need to set some priorities for how the agency reviews new drug applications. With the increasing speed of drug reviews, it may be under pressure to shorten the statutory timelines even further, while being asked to consider even greater flexibility in the types of data it will consider when making its decision.