Analysis

Statements in Support of a Limited-Population Antibacterial Drug Pathway

Developing new antibiotics for seriously ill patients with unmet medical needs is essential in the fight against superbugs. The Generating Antibiotic Incentives Now (GAIN) Act, which grants an additional five years of exclusivity (without generic competition) to new antibiotics that treat serious or life-threatening infections, was signed into law in July 2012 to help address the financial disincentives to antibiotic innovation.

Additional legislative efforts to facilitate antibiotic development for unmet medical needs are underway. The U.S. House of Representatives approved the Antibiotic Development to Advance Patient Treatment (ADAPT) Act in July 2015 as part of the 21st Century Cures Act; the Senate is considering companion legislation in the Promise for Antibiotics and Therapeutics for Health (PATH) Act. This legislation would create an approval pathway for limited-population antibacterial drugs (LPAD) to address the medical needs of patients with serious and life-threatening bacterial infections that are resistant to current treatments.

Below are statements from government officials, members of Congress, public health groups and other stakeholder organizations, doctors and pharmaceutical companies in support of LPAD.

Administration - Food and Drug Administration

Janet Woodcock, M.D.

Director, Center for Drug Evaluation and Research

“We would expect for the drugs to meet the usual standard of substantial evidence. However, substantial evidence as we interpret it for rare, life-threatening diseases is accompanied perhaps with more uncertainty than where we’d be treating headaches or diarrhea or diabetes or something like that, where there are millions of patients. So of course, there would be clinical trials. There’d be pharmacokinetics. There would be various studies. There would definitely be human studies of various sorts.” (Pew LPAD briefing, July 28, 2015)

“It’s our understanding that drugs approved using an LPAD pathway would be intended for that limited population that has the resistant organism. So that’s very different than the kind of broad approvals that we usually give in the antimicrobial space. And these would be serious or life-threatening [illnesses].

 “So people ask, is this lowering the standards? Well, actually, we approve many drugs on streamlined development programs all the time. We approve drugs for rare diseases that are serious or life-threatening. And here it’s been very well-documented that we use a streamlined development program, because number one, there are not that many patients with that disease [such as carbapenem-resistant Enterobacteriaceae], and number two, they have that unmet need that is very severe. And so those are the trade-offs between certainty—they’re not going to be able to wait 20 years until we accumulate enough people with that disease to do the kind of trials…[which], as you hear, aren't really that feasible.

“But to reiterate, this would not lower the standard. We’d still be using the standard of substantial evidence. And we would have evidence of safety from the development program. And there are different ways to do that. ... This is more like the approvals we do all the time for rare, life-threatening illnesses. And we’re seeing more and more of these [types of approvals], say, in the cancer area as we are doing precision medicine or personalized medicine targeted therapy.” (Pew LPAD briefing, July 28, 2015)

“FDA shares the Committee’s goal of advancing the development of new antibiotics through a new approval pathway focused on drugs intended for limited populations of patients with few or no available treatment alternatives and streamlining the process for updating antibiotic breakpoints. We look forward to continuing to work with the Committee on issues, including the inclusion of a branding element within the labeling of such products that will alert the health care community that these products are special, and should be treated as such, and provisions related to meetings and agreements.” (Testimony at legislative hearing on 21st Century Cures Act, House Energy and Commerce Subcommittee on Health, April 30, 2015)

Edward M. Cox, M.D., M.Ph.

Director, Office of Antimicrobial Products

“Clinical trials would be part of the [LPAD] package, and in fact the proposals that are out there describe that the efficacy standard is the same and recognizes that this is a means of balancing benefit and risk in the setting of unmet need for patients with serious infections, folks that don’t have treatment options. So, yes, clinical trials would be the basis for approval.” (Inaugural meeting of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, video, Sept. 29, 2015)

Margaret A. Hamburg, M.D.

Former Commissioner

“This pathway … is an attempt to fine-tune this difficult challenge that FDA grapples with every day of balancing risks and benefits in order to provide the best possible treatment to patients. … This is an effort to sort of reflect the realities of expanded disease that are burdening patients today. … FDA believes that having a legislative framework—[one] that enables really much more accountability in terms of stewardship on behalf of hospitals and clinics and pharmacists about this narrower use, and will add on some new labeling requirements that currently are not in the FDA arsenal—will better assure appropriate use.” (Aspen Institute, video, June 27, 2015)

President’s Council of Advisors on Science and Technology

“This would be an optional pathway under which sponsors could propose, early in the development process, to study a drug for a narrow population. Such drugs would be approved under a designation of Special Medical Use, signaling strongly to payors and prescribers the limited population that should be prescribed a drug.” (Report to the President on Propelling Innovation in Drug Discovery, Development, and Evaluation, September 2012)

“We recommended the development of a new pathway for initial drug approval by the FDA (which we called ‘Special Medical Use’) when a candidate drug had been shown to be safe and effective in limited, defined group of patients. A ‘Special Medical Use’ (SMU) pathway would provide a more rapid solution for patients and companies with a potentially more rapid, albeit more limited, path to market. In particular, PCAST [the President’s Council of Advisors on Science and Technology] cited the case of drugs against antibiotic‐resistant bacteria, where such drugs might be initially tested in the limited population of patients known or highly suspected to be infected with the relevant resistant pathogen.” (Report to the President on Combating Antibiotic Resistance, September 2014)

Congress

Senator Michael Bennet (D-CO)

“Senator [Orrin] Hatch and I are also working on the PATH Act, which will provide more certainty to patients and companies in the approval of the antibiotics. The CDC has estimated that 2 million Americans become sick every year from antibiotic-related infections, and at least 23,000 of them die. It’s particularly difficult for wounded warriors, who sometimes become infected with deadly pathogens for which there are no treatments. Under our bill, FDA would be able to approve antibiotics for the most deadly infections under the same standards of safety and effectiveness, but for a limited population of people that need it the most.” (Bipartisan Policy Center, keynote address, July 27, 2015)

“We need new drugs to fight antibiotic-resistant bacteria that are posing serious and unique challenges to health care professionals. This bill will encourage investment in new drugs that could save the lives of thousands of Americans each year.” (“Hatch, Bennet Reintroduce Path Act to Streamline Approval of Antibiotics,” news release, Jan. 16, 2015)

Representative Diana DeGette (D-CO)

“With respect to the antibiotics—we have people in hospitals who are getting terrible, terrible [infections] that cannot be treated right now. We don’t have the antibiotics. So we put some very narrow language in the bill to allow development for some antibiotics that could treat that very narrow group of patients, [under] strict controls that the FDA agrees with.” (“The Diane Rehm Show,” July 30, 2015, at 15:04)

Representative Eliot Engel (D-NY)

“Antibiotic resistance is a serious and growing threat in the United States and across the world. This important legislation gives the Food and Drug Administration the ability to quickly approve medications specifically designed to treat drug-resistant bacteria. Having actively worked for years to stop the spread of drug-resistant tuberculosis and having seen its tremendously damaging impact, it is important to give the FDA another tool in the fight to treat Americans stricken by these dangerous ‘superbugs.’” (“Green, Gingrey Introduce ADAPT Act to Safeguard Public Health,” news release, Dec. 12, 2013)

Former Senate Majority Leader Bill Frist (R-TN)

“And then lastly, let me just say another area I’m going to call some attention to is the need to accelerate the development of something. Again, it affects everybody in the room, and that is the use of antibiotics. And we see a lot in the press today, we know superbugs are an issue. But how can we—we know there’s a problem out there, we know people are dying from it, and it’s created by, in large part, by our use of other antibiotics. We need to accelerate innovation to cure it, to treat it … and the FDA needs to give a special attention to the approval of antibiotics for use in these limited populations, [to treat] the superbugs.” (Bipartisan Policy Center, panel, July 27, 2015)

Former Representative Phil Gingrey (R-GA)

“As a physician for more than 30 years, I understand the critical need for life-saving medical treatments. The ADAPT Act provides incentives for investment and innovation and is another step forward in developing treatments for patients with antibiotic-resistant infections.” (“Green, Gingrey Introduce ADAPT Act to Safeguard Public Health,” news release, Dec. 12, 2013)

Representative  Gene Green (D-TX)

“For decades, antibiotics have been taken for granted, but their effectiveness is waning and the pipeline for new drugs is running dry. We need to invest in new, effective antibiotic therapies in order to combat serious and life-threatening drug-resistant infections. The ADAPT Act, will build on the success of the GAIN Act, and serve as the next important step in advancing the development of new antibiotics.”  (“Green, Gingrey Introduce ADAPT Act to Safeguard Public Health,” news release, Dec. 12, 2013)

“We have the tools and authority to create a path for rapid development of safe and efficient new drugs. Drug resistance can be slowed, but it cannot be stopped. We have to act now.” (“President Calls for New Actions to Combat the Growing Threat of Drug Resistance,” news release, Sept. 18, 2014)

Senator Orrin Hatch (R-UT)

“America has always been a beacon for innovation and discovery. The PATH Act will allow health experts to more easily develop new treatments for antibiotic-resistant bacteria, and make real progress in preventing a great number of illnesses and deaths in the United States.” (“Hatch, Bennet Reintroduce Path Act to Streamline Approval of Antibiotics,” news release, Jan. 16, 2015)

Representative John Shimkus (R-IL)

“By creating a new, streamlined pathway for the most critically needed antibiotics and antifungals, thousands of lives can be saved each year.” (21st Century Cures Act floor speech, video, July 10, 2015)

“Addressing the lack of treatments for drug-resistant infections unites us above partisan, geographic and ideological differences. Without greater investment in new treatments, we face a future that resembles a pre-antibiotic era. The 21st Century Cures Act is a testament to what we can accomplish when we work together. I’m pleased this landmark legislation includes our provision to address the growing threat posed by antibiotic-resistant infections. By also introducing the ADAPT Act as a standalone bill, our colleagues will now have the opportunity to register their explicit support for this critical provision of the 21st Century Cures Act.” (“Crucial Antibiotics Bill Reintroduced,” news release, June 4, 2015)

Organizations

Letter from four leading public health organizations

“This legislation will establish a much needed pathway to deliver antibiotics to patients that desperately need them. Without such a pathway, we fear that antibiotic research and development will continue to decline, leaving a growing number of patients with untreatable, life-threatening infections.” (Letter from the American Public Health Association, Association of State and Territorial Health Officials, National Association of County and City Health Officials, and Trust for America’s Health, June 9, 2015)

National Venture Capital Association

(Bobby Franklin, president and CEO)

“We commend Senators Bennet and Hatch for introducing this important piece of legislation [the PATH Act]. This bipartisan effort is an example of steps we need to take to ensure that the United States remains the global hub for medical innovation and to promote investment in desperately-needed antibiotics that will improve the lives of everyday Americans as well as our veterans returning from overseas deployment.” (“Bennet-Hatch PATH Act Will Promote Investment in Medical Innovation,” news release, Jan. 16, 2015)

Science in Service to Humanity Foundation

(Rear Adm. James J. Carey, chairman)

“The time is right. There is broad support for updating the antibiotics approval process from industry and the nonprofit sector. There is bipartisan support on both sides of the Hill and at the White House. For the sake of our returning troops and the millions of people worldwide at risk of untreatable infections, I hope this legislation is among the first bills to pass the new Congress.” (“Congressional Action in the Fight Against Superbugs,” op-ed, Roll Call, Jan. 15, 2015)

Trust for America’s Health

“To avoid the vast and dangerous consequences of antibiotic resistance, TFAH calls for an immediate, comprehensive and coordinated approach. To start, we recommend that Congress and the Administration take action by incentivizing Development of New Drugs: Innovation of new antibiotics has stagnated. Congress should pass a limited population drug approval pathway for new antibiotics, like what was included in the ADAPT Act.” (“TFAH Issues Statement on the Threat of Antibiotic Resistance, Recommends Government Take Additional Action,” Sept. 18, 2014)

“Congress should develop new antibiotics by passing a Limited Population Antibiotic Drug approval pathway to promote innovation of novel, life-saving antibiotics.” (“Public Policy Priorities 2015, 2016,” February 2015)

Private sector

Achaogen Inc. (Kenneth Hillan, CEO)

“Achaogen also supports passage of the ADAPT (Antibiotic Development to Advance Patient Treatment) Act and the establishment of new regulatory approval pathways for antibiotics that target specific and limited patient populations with high unmet medical needs. The ADAPT Act will provide FDA with increased flexibility, beyond what is currently available, to promptly approve those agents intended to treat serious and life-threatening infections based on evidence that may come from clinical datasets of limited size, supplemented by pharmacologic or pathophysiologic data and phase 2-type studies. …

“ADAPT is important to manufacturers of antibiotics designed specifically to treat multidrug resistant (MDR) infections because it provides an alternative regulatory mechanism that allows for more rapid access [by] patients based on limited data in that population. … Congress must enact legislation that authorizes the FDA to approve new antibiotics for limited patient populations based on limited clinical trial data but where the totality of the available scientific and clinical evidence supports the benefit/risk profile for the antibiotic, while acknowledging and reflecting the greater uncertainty associated with limited clinical testing in the product label.” (Testimony of Kenneth Hillan on 21st Century Cures Act, House Energy and Commerce Subcommittee on Health, Sept. 19, 2014)

Additional stakeholders

William Schaffner, M.D.

Professor, Vanderbilt University School of Medicine

Patty Wright, M.D.

Associate professor, Vanderbilt University School of Medicine

“New legislation in Congress could clear some of the regulatory hurdles drug makers face. Introduced by Sens. Orrin Hatch (R-Utah) and Michael Bennet (D-Colo.), the Promise for Antibiotics and Therapeutics for Health, or ‘PATH,’ Act aims to promote antibiotic development by creating a new pathway to approve these new drugs for patients who are out of options. Similar legislation is being considered in the House Energy and Commerce Committee. 

“The bills provide for more feasible clinical trials with limited numbers of patients who are battling dangerous bacterial infections like CRE [carbapenem-resistant Enterobacteriaceae]—patients with few, if any, options for treatment. They also outline safeguards to make sure the drugs are used with great care, and their approval does not contribute to the problem through overuse. 

“The latest outbreaks demonstrate the continued and growing threat of antibiotic resistance. As physicians who are deeply troubled to see more and more patients with drug-resistant infections, we are gratified to see more attention to this issue. We hope Congress continues to recognize the urgency of this problem and passes PATH soon—for the sake of every patient, and the safety of society as a whole.” (“Open a ‘PATH’ for New Antibiotics,” op-ed, The Hill, March 18, 2015)

Helen W. Boucher, M.D.,

Associate professor, Tufts University School of Medicine

“So that brings us to the PATH Act. And the hope is that this act will allow us to get antibiotics studied in a way that’s meaningful and feasible for our patients. The issues with studying patients with these infections are pretty complicated. It’s hard to find patients who can consent for trials. It’s hard to fund these kinds of trials. These patients are very sick, and it’s expensive to study them. So the idea is that this act would allow studies that are feasible to be done in a way that can show that the antibiotics are safe and effective according to the FDA standards. There is no lowering of the standards. But it’s a way to allow a path—no pun intended—forward, so that we can get the antibiotics that our patients desperately need. So I’m going to come back to the fact that antibiotics are the most precious gift we have. We all have an obligation to protect and preserve the ones that we have and help get new ones for our future patients.” (Pew LPAD briefing, July 28, 2015)

Jonathan Leff

Venture capitalist

Allan Coukell

Senior director of health programs, The Pew Charitable Trusts

“To revitalize the search for lifesaving antibiotics, the Food and Drug Administration needs a new way to approve them. Legislation proposed in both the House and the Senate would create a new regulatory pathway that would enable FDA to approve drugs specifically for patients whose serious infections can’t be treated with existing drugs, and for whom there are few or no other treatment options.

“For these patients, FDA would be empowered to approve new drugs based on fewer or smaller clinical studies than for antibiotics intended for broader use. The goal is to reduce the cost of development and accelerate the availability of new drugs for a targeted public health need.” (“How to End the Regulatory Slowdown for New Antibiotics,” op-ed, The Wall Street Journal,  July 2, 2015)

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