Countdown to Cures

Since The Medicine Maker first launched in September 2014, we’ve covered many ‘next generation’ developments – from personalized medicine to nanotechnology to new manufacturing techniques – that have the potential to advance the pharma industry and healthcare. But harnessing the latest scientific breakthroughs for the benefit of humankind takes time... Too much time, apparently. Indeed, there are those who argue that regulatory hoops are unnecessarily delaying innovative new therapies; they say, “medicine has changed, and regulation must change with it.”

Admitting that the current law has not kept pace with innovation, US legislators are developing a new bill: the 21st Century Cures Act. Its main purpose? To modernize approval processes for new medicines, particularly for conditions where other treatment options are lacking.

The (Highly Abridged) 21st Century Cures Act

Discovery

• NIH funding
• NIH planning and administration
• Supporting young emerging scientists
• Facilitating collaborative research

Development

• Patient-focused drug development
• Qualification and use of drug development tools
• FDA advancement of precision medicine
• Modern trial design and evidence development
• Incentives of certain products for limited populations
• Enhancing combination products review
• Domestic manufacturing and export efficiencies
• Sensible oversight for technology which advances regulatory efficiency

Delivery

• Interoperability
• Telehealth
• Disposable medical technologies
• Medicare pharmaceutical and technology ombudsman

The latest draft of the Act (which has been in development since April 2014 and revised twice in 2015 already) is over 300 pages long and includes dozens of sections, covering discovery, development (the most extensive area in the draft) and the delivery of new medicines to patients (1, 2). If the Act becomes law, it could have a significant impact on drug development; for example, requiring the FDA to provide guidance on topics such as precision drugs, biomarker development, and incorporating adaptive designs and Bayesian statistical modelling into clinical protocols. For some examples of sections included in the latest draft that companies should begin to look at if they want to stay ahead of the game, see “The (Highly Abridged) 21st Century Cures Act”.

“When the Affordable Care Act was implemented several years ago (which also led to the Sunshine Act coming into play) some companies were behind the times and unprepared for aspects such as electronic health care records,” says Garrett Davis, a research associate at Best Practices LLC, and author of a white paper released in March (3). “It’s important to get ahead of the curve, to understand the rules and legislation that will be coming down with the 21st Century Cures Act, and to plan for what is there now with the understanding that there will probably be more changes.”

So, you need to be prepared for change, but there’s also the question of what impact the draft – and further amends – will have on the FDA. In particular, can the FDA keep up? Dale Cooke from PhillyCooke Consulting comments, “I’m excited at the increased funding for the National Institutes of Health (NIH). NIH has been underfunded for a long time, but I’m also concerned that the 21st Century Cures Act includes massive changes for the FDA, and the funding being discussed doesn’t seem commensurate with the changes. The FDA keeps getting expanded responsibilities and not quite enough funding to meet those responsibilities. FDA employees only have so many hours in the day and if you require that they spend time drafting certain specific guidances, then by definition they won’t be working on other topics, unless you give them enough resources to cover the expanded workload.”

According to Rachel Sachs, an academic fellow at the Petrie-Flom Center at Harvard Law School who has been following the Act with interest, 21st Century Cures has the potential to completely overhaul the existing system for bringing new treatments to the public. “The titles of the three main parts of the Act say it all. Often, a statute will address a single one of these goals. For instance, the ‘Doc Fix’ legislation passed in April 2015 addressed the Medicare delivery system, and every five years a new version of the Prescription Drug User Fee Act presents an opportunity to alter the FDA’s review process. An opportunity to address all three important areas – discovery, development and delivery – at once is potentially very exciting.”

The politics of change

It was over a year ago that the US Energy & Commerce Committee, headed by Fred Upton, first announced its intent to work on a new Act concerning medicine development, and a number of roundtables were held in 2014 followed by a series of white papers. But it was all hearsay until a draft for discussion finally appeared in January 2015. “It was a huge 393-page document, covering all of the different issues that they wanted to include in 21st Century Cures,” explains Davis. “Many of the elements in the draft came from little bills and acts concerning drug discovery and development that never made it to final approval. The discussion draft also contained open fillers – parts they wanted to add in but had no idea what to write at the time. These topics have been discussed with trade associations, bio/pharma companies and patient advocacy groups.”

The first draft was met with both praise and criticism – but also politics. Davis says, “Chairman Upton (Republican-Michigan) partnered with Representative Diana Degette (Democrat-Colorado) to make this a bi-partisan act. However, the initial draft document was not publically endorsed by Degette. Since the draft was subject to change it has gone though two different updates. Now, it has been unanimously approved by the Energy and Commerce Committee, which is a rarity.”

But the changes to the drafts have been significant. “The first version was nearly 400 pages long, even with several sections listed as ‘to be supplied’. The second version was much shorter, at just 200 pages, but the third is back up to 300,” says Sachs. “There are many major additions and deletions. For example, the second version of the Act added provisions creating a separate NIH Innovation Fund, which would increase the agency’s budget by $2 billion a year for five years. Total NIH funding has been stagnant or decreasing for many years now, with sequestration and budget cuts, and these funding increases are hugely important.” The first version of the Act also contained a provision that would have given drugs intended for “unmet medical needs” fifteen years of FDA exclusivity. “This was one of the most controversial parts of the Act, and it’s not present in the second or third version of the document,” Sachs continues. “The argument in favour of the provision is that it would promote more investment into drugs for ‘unmet medical needs’. In my view, the proposal would likely have encouraged some research that wouldn’t otherwise have occurred, but the much greater effect would be to replace the five, seven, or twelve years of exclusivity given to most drugs at present with a fifteen-year period, increasing costs for both consumers and the government. Even now, most drugs are approved to treat ‘unmet medical needs’. The provision wasn’t narrowly tailored enough to avoid the effects on consumers that we often worry about in this context.”

Cooke also noted that sections concerning social media have been omitted from the later drafts: “The first draft included a provision that would have required FDA to revise existing regulations and guidance to accommodate so-called ‘one-click’. Because FDA has never endorsed any one-click provision, there are several different versions of the idea floating around,” he says. The basic concept of one-click is that it allows prescription product marketers to provide ‘some’ information about risks a single click away from the initial message on benefits. “FDA has repeatedly taken actions that demonstrate it does not endorse such a view, but the first draft of the Act would have mandated FDA to change its position. However, the ‘one-click’ provision was removed at FDA’s request and has become a piece of stand-alone legislation sponsored by Congressman Billy Long,” says Cooke.

And despite the significant revisions  already made, aspects of the latest draft remain hotly contested. An article written by two doctors raised concerns that the Act would lower the standards for approving new uses of existing medicines. The latest draft, if implemented, would encourage FDA to approve drugs on biomarker information rather than clinical trials (4).

“However, all of the discussions we’re having about the Act are fairly speculative, and it might be that the FDA is able to circumvent the intent of Congress in various ways,” says Sachs. “For instance, the Act instructs the FDA to issue guidance regarding the development of biomarkers. The intent is clearly to encourage the FDA to rely more on biomarkers and less on true endpoints in evaluating drugs for approval; the question is whether the FDA would take advantage of that discretion. It might feel pressured to do so, but it’s not clear that it necessarily has to relax its standards in a harmful way.”

Be prepared to keep up

The Act has passed a unanimous vote from the US House Committee on Energy and Commerce and will now pass to the full House of Representatives. That said, full implementation is still some way off; even after the Act has been passed, the rollout will be staggered. “The Senate will still have to pass its own bill on the subject. Although the Senate Health, Education, Labor, and Pensions Committee has released a report suggesting that it is largely in support of the House’s efforts, there is no draft bill in the Senate just yet, and most observers think it is likely to be months before they move on the subject,” says Sachs.

Davis agrees that it will take time. “I can almost guarantee that a lot of this stuff will not make it to the final version. The initial expectation was that the 21st Century Cures Act would be in the President’s office for final sign off by the end of this year, which would be fantastic, but I’m not sure it will happen. That said, the people involved want to move this forward as fast as possible. In 2016, the House, the Senate, and political and advocacy groups will all be focusing on the next Presidential Election, which would put 21st Century Cures on the back burner.”

There is clearly a great deal of uncertainty on the timing and content of the Act – and that could leave you feeling reluctant to consider its implications. But Davis says, “Even if just 10 percent of the current draft is implemented, it will drastically change how things work in the industry. And that’s why in these early stages, companies should be following it closely. As it gets closer and closer to becoming a reality, I can see a lot of people scrambling to figure out exactly what’s going on.”