expanded access application

FDA struggles to react to ‘right to try’ laws

GAO report notes FDA’s 99% acceptance rate for ‘expanded access’, but legislators press on

Now in place in 37 states, so-called ‘right to try’ laws seek to remove any federal obstacle for desperately ill patients to obtain experimental drugs that have passed Phase I (the safety step). Now, a GAO report finds that FDA continues to impose few hurdles to physicians or their patients in approving the request (or, at least, not threatening to impose sanctions on manufacturers who would provide the non-approved drug). For the fiscal years 2012-2015 inclusive, FDA allowed 5,697 of 5,753 requests to proceed. GAO’s report, “FDA has taken steps to improve the expanded access program but should further clarify how adverse events data are used,” summarizes the pharma industry’s perspective as “[some] manufacturers noted that the lack of clear information can influence their decision whether to give patients access to their drugs because of their concerns that an adverse event will result in FDA placing a clinical hold on their drug, which could delay its development.”

Expanded access, aka “compassionate use,” also exists in the EU as “named patient” programs. In the US, this dispute has been going on for years; FDA’s own policies were revamped in 2009 and again in 2016, when the current streamlined application form (FDA 3296) was issued. Since around 2014, however, the Goldwater Institute, a libertarian-leaning advocacy group, has been pushing state by state for right-to-try laws. And now it has the ear of Vice President Mike Pence, who met with the Institute early this year; President Trump is also said to be in favor of the laws. Legislation similar to the state laws has been proposed multiple times in the US Congress; however, the FDA Reauthorization Act of 2017 (HR 2430, which passed the House by voice vote on July 12) only included a request for a public hearing on clinical trial access and expanded use, and Senator Ron Wyden (R-WI) has threatened to hold up the legislation in the Senate unless right-to-try language is included. The 21st Century Cures Act, one of the last laws signed by President Obama in December, includes an obligation for manufacturers to publish their expanded access policies, in addition to streamlining aspects of the clinical trials approval process that could make drugs more quickly available. In early July, FDA Commissioner Scott Gottlieb (who has written extensively on a risk-averse culture at FDA prior to taking its reins) issued a long list of FDA actions to be taken in light of the 21st Century Cures Act, including streamlining trial procedures.

It’s not clear, at this point, whether the right-to-try laws in place in many states has resulted in any change to patient access. None of the laws require a manufacturer to provide an investigations drug; nor is there any requirement for commercial or public insurance to pay for expanded access drugs. There is something of a track record, going back to the AIDS activist era in the 1980s, of mobilized groups essentially shaming a drug company into providing investigational drugs. Under current FDA guidance, a drug manufacturer can prepare, in a fashion, for multiple expanded access requests by including an expanded-access protocol in its FDA regulatory filings. (In this case, the manufacturer itself becomes the requester of expanded access.)

Another action that FDA had taken in 2016 was to authorize the Reagan Udall Foundation, a nonprofit public group set up by Congress to backstop a variety of FDA initiatives, to design an Expanded Access Navigator to help patients and their physicians in preparing applications. That site has already been “soft launched” according to a Foundation spokesperson. It includes a list of the 31 pharma companies who have already written (and informed FDA) of their expanded access selection criteria.

All this legislating and advocacy work, by the Goldwater Institute and other right-to-try advocates, sounds like real progress has been made to assist terminally ill patients, but the end result is still a question mark. On its website, the Goldwater Institute states that “While millions of Americans will be diagnosed with or die of terminal illnesses each year, compassionate use exceptions are only granted to about 1,000 patients a year”—which gives an indication of how overwhelming expanded access could be for companies with limited stocks of a drug that is being produced for trials. The right-to-try laws usually specify that FDA not take into account adverse or other events the occur when a patient is given expanded access treatment; but researchers rightly point out that it is absurd for scientists not to look at pertinent evidence wherever it can be found.

And while there is earlier regulatory action on how an expanded-access drug is to be priced, economics factors into the equation. At one academic blog, a leader in stem cell research is quoted that “There are scores of companies in the United States who want to sell unproven and scientifically implausible stem cell therapies to patients, some of whom are among the main supporters of right-to-try legislation.” Coming at the subject from a very different direction, at least one company, Inceptua, was recently founded to make a business from connecting patients with expanded access drugs.

In abstract, right-to-try laws are an assault on the very essence of FDA: keeping scientifically unproven drugs off the market, to protect patients and steer healthcare dollars (no matter who pays them) to useful purposes. Shutting down FDA’s drug approval process nearly completely (except, perhaps, for some Phase I safety studies) has been an idea kicked around in libertarian and far-right circles for years; even now, the accelerated approval mechanisms FDA currently employs are being watched for signs that the review process is being short-circuited. It could be that if Commissioner Gottlieb’s goal to speed up reviews and approvals pay off, the right-to-try movement will be mollified.