By Angela Woodall, Healthcare and Environmental Reporter.
Looking back at 2017, a year of change in leadership, legislation, investment and innovation at almost every level, two events stand out. The first is the 21st Century Cures Act, a jumbo spending package that began rolling out this year. The second is the 2017 reauthorization of the User Fees Act, a funding lifeline to the FDA. Not only did the two acts inject millions into the industry, but each influenced the direction in which the money would be spent. Specifically, the Cures and User Fees acts are intended to support novel therapies and devices, new approaches to clinical trial design, and new policy approaches to oversight and approval.
Funding in 2017
Regenerative medicine received only a fraction – $30 million – of the $6.3 billion Cures Act. But that still amounts to $30 million worth of incentives to accelerate the approval of regenerative medicine products. Indeed, Robert Preti, Chairman of the Alliance for Regenerative Medicine advocacy group, called 2017 an “inflection point” for the field.
Money to sustain innovation in regenerative medicine will also come by way of the FDA’s User Fee Act, which Congress reauthorized mid-year. The act funds at least a quarter of the agency’s budget. The re-up ignored a call by the White House to make user fees the primary funding source for the agency. But Congress did approve a change to the prescription drug user fee (or, PDUFA) structure: 20 percent of that revenue will come from application fees and 80 percent from program fees. In exchange, the new version eliminated supplemental application and facility fees.
The largest single investment will be in encouraging more patient engagement, according to Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER). But the legislation also instigates changes in protocols and clinical trial designs (look for the FDA to convene workshops on these and other practices). In addition, biosimilars will have their own fee structure for the first time, including the Initial Biosimilar Development Fee, assessed the first year after a clinical trial begins.
FDA guidance and announcements
Both the Cures Act and 2017 user fee legislation focus on adaptive trial designs and a diverse pipeline of breakthrough therapies leading to pivotal-stage trials. The FDA has responded with a spate of new directives intended to establish a new framework for breakthrough therapies. Interesting, the FDA signaled a willingness to increase outsourcing in order to accomplish its goals. Other highlights include:
- FDA accelerated approval without surrogates
- The new FDA Patient Engagement Advisory Committee (PEAC)
- Informed consent requirement waivers in minimal-risk studies
- An FDA-NIH harmonized template for NIH-funded late-phase trial protocols
- Grants for clinical trials developing treatments for rare diseases
- Recognition of inspection regimes of international drug regulatory authorities
This year also marked the launch of a program realignment in the FDA. Trials will now interact with the newly created FDA Office of Bioresearch Monitoring Operation, or OBIMO, and expertise is product-based instead of geographically determined. According to an email from the agency’s Office of Regulatory Affairs, the impact of the initiative on directly the conduct or design of clinical trials will be indirect: The product centers review the applications and data submitted. The difference that industry will see when interacting with investigators is that they will develop more specialized expertise, meaning they conduct only bioresearch monitoring inspections. “The outcome will be that investigators will be more knowledgeable, experienced, effective and efficient than they had been when working across multiple programs.” That’s good for the safety of products but may mean that sponsors and CROs need to anticipate inspectors with more detailed questions when they get to the trial or the manufacturing site.
Breakthroughs past and future
The FDA has been emphasizing easing the process for drugs and devices aimed at rare diseases. But striking progress has also been made in neurological treatments. The volume of treatments in the clinical trials phase is growing and patients are expecting results from a number of potentially breakthrough trials underway. In the meantime, new treatments have been rolling out, including Spinraza, Ocrevus and Crenezumab. The SPRINT-MS Phase IIb biomarker study of ibudilast (MN-166) reported achieving its endpoints. In addition, recent progress using adult mesenchymal stem cells has prompted optimism among patients with ASL, Parkinson’s and Huntington’s diseases that neurological research is ready to progress into critical-stage clinical trials.
The industry, trying to find a payoff in novel therapies, is showing enthusiasm as well.
- Approval of the first ingestible sensor-embedded drug, Abilify Mycite
- Novartis moved the industry into gene therapies with the first FDA-approved chimeric antigen receptor T cell (CAR-T) therapy, called Kymriah
- Merck’s breakthrough immuno-oncology treatment Keytruda received the FDA’s first approval of a therapy that treats tumors with a biomarker. The drug has since returned disappointing results but Merck is pushing forward with subsequent trials.
- Gene Editing — including CRISPR/Cas9 gene-editing technology — is attracting major investments from Big Pharma: just four deals between 2012 and 2017 were worth $1 billion and the first human trials.
A South San Francisco neurodegenerative disease developer, Denali Therapeutics, raised $250 million and captured the attention of analysts with the biggest biotech IPO of the year. Results from trials involving everything from Alzheimer’s to MS are expected to post in 2018. So it is not hard to imagine VC cash looking for a good home, or tech entrepreneurs searching for new start-up territory in therapeutics. In fact, Facebook co-founder Sean Parker invested $250 million in a cancer immunotherapy institute, a sector awash in takeover rumors.
Taken as a whole, it would not be an exaggeration to say that innovation on every front — new policies, new treatments and new ways of thinking about clinical trials — made an appearance in 2017. The direction is unlikely to shift in the coming year: Confirmed as FDA commissioner in 2017, Scott Gottlieb pledged continued efforts to speed approvals of therapies and devices in the coming months and announced a new “policy approach” for developing regenerative medicine products. The last big hurdle will be understanding how the federal tax plan will play out for CROs, their clients and the industry as a whole.
PRC is celebrating its 15th year anniversary in 2018 with conferences and events, starting with the Outsourcing in Clinical Trials West Coast Conference in Burlingame, California. We’ll also be publishing special reports and offering giveaways. In the meantime, you can keep up with PRC blogs and ClinPulse events here.