Senators Bennet, Hatch, and Burr advance legislation for breakthrough therapies

U.S. Senators Michael Bennet (D, CO), Orrin Hatch (R, UT), and Richard Burr (R, NC) introduced a smart, thoughtful bill yesterday (Advancing Breakthrough Therapies for Patients Act) designed to move innovative products to patients faster. The legislation is also supported by the cancer advocacy group Friends of Cancer Research and the National Venture Capital Association.

First, a little background. If enacted, this would be the first reform of the FDA's drug approval process for innovative new therapies since Accelerated Approval (AA) was enacted by the agency in 1992 and Fast Track created as part of the FDA Modernization Act in 1997.

So it's either been 15 or 20 years since the FDA or Congress has made any attempt to systematically expand pathways for new therapies.

How well has AA worked? For HIV/AIDS and cancer patients and some orphan indications, very well. The vast majority of drugs that have received AA have been for those indications because the agency has more confidence in surrogate markers for those diseases for other diseases. As a result, cancer and HIV therapies reach market years faster than if they had been required to complete full Phase III trials before marketing approval.

In cancer in particular AA has led to an explosion of investment, research, and clinical trials testing new medicines. But we can't recognize the value of AA for cancer and HIV and somehow say to patients with other serious and life-threatening diseases that "sorry, you'll have to wait at the back of the line until we sort things out for you."

It wasn't as if the FDA woke up one morning and just created AA out of thin air. It took smart and savvy AIDS protestors demanding that the FDA change how they evaluated new treatments - both through public protests and targeted (science-based) policy demands.

It's time - long past time - to update and expand AA for the millions of patients who could benefit from science-based reforms. As John Marangore, CEO of Anylam Pharmaceuticals, put it in recent Congressional testimony:

...there are several reasons why the Accelerated Approval pathway should be expanded and modernized. First, it is important that the ability to utilize an accelerated pathway is better understood by sponsors and more consistently applied by FDA. This is especially true when it comes to FDA accepting clinical endpoints, including those that can be measured earlier than irreversible morbidity or mortality, to demonstrate a reasonable likelihood of clinical benefit.

While the pathway, which was codified in 1997, allows for approval based upon effects on clinical endpoints that are reasonably likely to predict clinical benefit, in practice the lack of clarity surrounding such approval options has led to very limited use by sponsors and FDA.

Additionally, the Accelerated Approval pathway has been largely limited in practice to drugs that treat cancer and HIV/AIDS, along with a handful of other situations, leaving many other rare and serious conditions effectively excluded from the pathway and creating confusion among sponsors on how to apply the pathway to these indications.

The Breakthrough Therapies bill (Pharmalot links to a copy of the legislation here) would, in a nutshell:

Create a flexible pathway for the FDA to evaluate products to "treat serious or life threatening disease or conditions" when preliminary clinical evidence "indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints."

Require the FDA to take action to help facilitate the development and review of breakthrough products, including holding additional meetings, offering advice, facilitating cross-disciplinary reviews, and having a project lead "facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor."

The legislation also encourages the FDA to ensure that the design of clinical trials is as efficient as possible (and scientifically appropriate). This is particularly important since clinical trial costs and development times are skyrocketing, helping to drive up drug prices and delay access to innovative therapies. (Smaller, leaner, faster ought to be the agency's motto when it comes to helping to develop breakthrough therapies.)

The legislation also sets deadlines (always helpful for focusing regulators' attention) for draft and final guidance for sponsors on how to seek breakthrough, accelerated approval, and/or fast track designation.

The most important section of the legislation may be the clause that requires the Secretary of HHS to commission an independent entity to asses the "quality, efficiency, and predictability" of how the FDA has applied the directives in the legislation no later than four years after the bill passes.

That may the best way to ensure that we won't have to wait another 15 or 20 years to understand how well the FDA is utilizing the authority granted it by Congress.

The core ideas in this legislation are, as Senator Hatch observed, "common sense" reforms. They should only help Commissioner Hamburg and senior FDA staff institute the management and scientific reforms that they've been talking about for several years now. But the track record of the FDA is that it only innovates under pressure - from a public health crisis or at explicit Congressional direction.

Hopefully, the core elements of this legislation will be incorporated into the upcoming PDUFA reauthorization. But PDUFA is also a double edged sword, because without the legislation the FDA will have to start firing reviewers and slowing down new drug and device approvals, something no one (industry, patients' groups, Congress) wants.

PDUFA is, indeed, a "must pass" bill.

But getting a timely PDUFA bill passed is no excuse for Congress to neglect its fundamental responsibility of ensuring that the FDA is reviewing innovative new therapies as quickly and effectively as possible, using the best scientific and management tools at its disposal. Losing or neglecting this opportunity may push off critical FDA reforms for another 5 years - when we'll just have to battle another tight PDUFA deadline.

And that's how 15 or 20 years pass by without anyone driving the kinds of "common sense" FDA reforms suggested by Senators Bennet, Hatch and Burr.

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