21st Century Cures Update: Ebola Hearing October 16, FDA’s LDT Draft Guidance

This past July we wrote about the 21st Century Cures initiative and its efforts to bridge the gap between medical advances and the regulatory policies that govern them. The initiative, a bipartisan collaboration between Rep. Fred Upton (R–MI), chair of the Energy and Commerce Committee, and Representative Diana DeGette (D–CO), one of the panel’s senior Democrats, aims to examine the “full arc” of the innovation process to get new treatments and cures to patients more quickly and streamline the drug and device development process. Some of the initiative’s recent activity is summarized below.

Antibiotic resistance and new drug development

In September, the Energy & Commerce Committee’s Subcommittee on Health held a hearing to review the growing threat of antibiotic resistance and discuss ways to foster new drug development. Witnesses testified as a part of the committee’s 21st Century Cures initiative, pushing for better incentives to create new drugs, streamline clinical trials for highly resistant drug development, and consider changes to exclusivity periods for new drug development.

The Energy & Commerce Committee Chairman, Fred Upton (R–MI), stressed that antibiotic resistance and the need for new drug development illustrates the kind of public health crisis 21st Century Cures is intended to combat.

Adding FDA’s perspective, Dr. Janet Woodcock, Director of the agency’s Center for Drug Evaluation and Research (CDER) stated a desire to work with stakeholders like 21st Century Cures. “It is virtually undisputed that we are facing a tremendous public health crisis because of the rise of serious antibacterial infections and the simultaneous decline in R&D in this area,” she said. “FDA is using the tools we have to begin to strengthen the antibiotic drug pipeline. However, more work is needed to improve the current climate, and FDA is looking forward to continuing to work with stakeholders to address this public health crisis.”

Dr. Adrian Thomas of Janssen Global Services stressed the need for more drug development through the mobilization of innovators in the scientific fields. “In the design of policies to meet this need of growing magnitude, focus must be fixed on the end goal, namely: more therapeutic and preventive options for patients, sooner … To achieve this, we must foster more ‘shots on goal,’ galvanizing and mobilizing the larger innovator community to apply its time, talents and resources to the challenge of antibiotic resistance.”

Additionally, the hearing addressed the topical issue of Ebola, and Boston University Law Professor Kevin Outterson added that research programs require at least a decade and often longer to deliver an effective antibiotic, so the need for innovation and more research is of paramount importance.

***On Thursday, October 16 at noon, the Subcommittee on Oversight and Investigations, chaired by Rep. Tim Murphy (R-PA), has scheduled a hearing on Ebola. Tom Frieden, Director of the Centers for Disease Control and Prevention, and Dr. Anthony Fauci, Director of the National Instutite of Allergy and Infectious Disease at NIH, will testify with additional witnesses to be announced. Committee leaders sent a letter to Health and Human Services Secretary Sylvia Burwell on September 12, 2014, seeking more information about the outbreak and the government’s preparedness and response efforts. 

Praise from The Denver Post and New Bill

Celebrating the bipartisan efforts by Colorado Democratic Rep. Diana DeGette and House Republicans, The Denver Post Editorial Board called 21st Century Cures “an ambitious effort to restructure funding and regulations around biomedical research to foster innovation and life-saving products.” The Post noted the intuitive might help accelerate biomedical breakthrough and ensure the United States retains its lead as the center of innovation.

The Post reports that Reps DeGette and Upton have spent several months seeking advice from a broad spectrum of experts associated with biomedical research, including scientists to regulators to investors. They intend to draft a bill by year’s end to introduce in the next Congress.

Specifically, Rep. DeGette pointed to several problem areas that need attention:

Reliable funding. Although funding for NIH was doubled in 2001, it has lost 25 percent of its buying power since because of budget freezes and cuts.

The obsolete structure of the federal agencies, which slows down approvals. As a result, a 21st Century white paper explains: “the timelines, size, failure rates, and costs of conducting trials [for new therapies] are at all-time highs, with administrative and regulatory burdens often contributing to such increases.” Indeed, the cost of developing a new drug now exceeds $1 billion.

Lack of a centralized registry for those engaged in biomedical research. “If you had a registry — with informed consent for patients — then you could have one pipeline to get those big studies done,” DeGette said. Large-scale genome trials could be done much more easily, she added.

Roundtable on biomedical innovation 

Also in September, the 21st Century Cures initiative held a “high-tech town hall on biomedical innovation, with tech companies, patients’ groups, drug companies, and hospital systems all reflecting on barriers to innovation—and how to overcome them.” View the roundtable here.

The initiative points out that a consistent theme thus far in Energy & Commerce hearings is that innovation must be a team sport. The hearings often note that private industry can only reach its full potential with a steady flow of new scientific discoveries that it can translate into new technologies. Support for government investment increases when basic research delivers tangible benefits in the form of better health, longer lives, and high paying jobs generated by a robust biotechnology industry.

Specifically, the hearings have generated a number of ideas to advance “team-based” innovation. Four of the biggest include:

1. Update FDA regulations to harness the full potential of modern technologies to advance targeted treatments to patients. 

Today, according to the Tufts Center for the Study of Drug Development, it costs an average of $1.3 billion and as much as 15 years to develop a single new FDA-approved medicine. Only about 1 in 3 medicines that make it to market even recoup their R&D costs. The enormous regulatory uncertainty and sunk costs facing innovators translates into lost opportunities to use cutting-edge science to advance state-of-the-art care, while resulting in higher prices for FDA approved medicines.

The initiative argues for a new development paradigm that allows the healthcare industry to deliver customized cures to patients much faster and less expensively than is currently possible. One approach is to expand the FDA’s current accelerated approval pathway, where drugs are approved earlier in the development process, based on surrogate endpoints or “biomarkers” that give an early read on whether the drugs are reasonably likely to deliver clinical benefits later. Congress could require FDA to pilot an expanded system like this for every disease with serious unmet medical need, particularly in targeted groups of patients. In fact, this exact approach was recommended by President Obama’s Council of Advisors on Science and Technology in 2012.

2. Make patients true partners in advancing medical research. 

Currently, data that could be used to advance personalized medicine is lost because health care systems cannot effectively share data, while providers are reluctant to pool data out of fear they will run afoul of federal regulations, such as HIPAA. Another research protection, the Common Rule, restricts researchers’ ability to go back and reanalyze data or tissue samples using new tools or diagnostics if they weren’t spelled out in the initial patient’s informed consent form.

The initiative states that patients must own and control their own health data, with appropriate privacy protections, while also allowing for broader informed consent forms that facilitate pooling and ongoing analysis of de-identified clinical trial, outcomes data, and even data from the emerging field of wearable diagnostics.

3. Ensure a stable, predictable source of funding for basic medical research. 

The initiative points out that if one looks at America’s most successful biotech hubs—from Boston to San Francisco—you will find that NIH driven medical research at hospitals, universities, and academic medical centers creates the knowledge base that private industry uses to launch their search for new cures. Basic science, applied technology, and the profit motive work together to drive a virtuous cycle of medical innovation.

To sustain the industry’s pipeline of new products, NIH needs a predictable, sustainable source of funding, particularly to help young researchers launch their careers. Doubling the NIH’s budget again may not be in the cards, but a predictable stream of funding would be immensely helpful. Pegging NIH funding to GDP growth would be one way of insuring steady funding, perhaps in tandem with additional reforms to ensure that NIH funded projects are, in fact, generating reproducible science.

4. Develop robust incentives for innovators working on hard to treat diseases like Alzheimer’s.

In addition to modernizing FDA’s regulatory toolkit and supporting NIH’s critical research, the initiative states that policymakers must ensure there are adequate market incentives to drive large, ongoing private investments in disease areas where the scientific hurdles are especially complex (like central nervous system disorders).

For instance, proving that a drug or vaccine prevents Alzheimer’s might require clinical trials lasting decades—exhausting any product’s effective patent life. One simple solution would be to guarantee 12 or 15 years of patent life for any product that passed FDA approval for Alzheimer’s, schizophrenia, or Parkinson’s. This would help encourage companies that have exited the CNS space—like AstraZeneca and Novartis—to get back into the fight. Innovators need to know that if they embrace the financial and scientific risks inherent in developing new treatments, their investments will be able to reap significant financial rewards when they finally do reach patients.

FDA regulations on laboratory developed tests (LDTs)

In August, we wrote about the FDA’s action notifying Congress that it intends to issue draft guidance to propose a risk-based, phased-in framework for oversight of laboratory developed tests (LDTs) and has provided the anticipated details of the LDT guidance in the notification. Stakeholders are concerned about the regulation’s potential requirements. 

“21st Century Cures: Examining the Regulation of Laboratory Tests” aimed to provide the Health Subcommittee with a better understanding of how LDTs are performed in clinical practice, what their impact has been on personalized medicine, and how we can continue to foster innovation in this space.

Rep. Joe Pitts (R-PA), chair of the Subcommittee on Health, said the FDA regulation would “fundamentally alter the regulatory landscape for the review and oversight of LDTs and the clinical labs that develop them”. He raised concerns that the regulation must consider and encourage robust investment and allow for continued innovation.

Responding to questioning from Rep. Morgan Griffith (R-VA), FDA Director of the Center for Devices and Radiological Health, Dr. Jeff Shuren testified that part of the agency’s reasoning for including a new notification option under the proposed guidance was to allow businesses an opportunity to avoid the health law’s medical device tax.

A number of other witnesses testified with varying viewpoints, although members of the Subcommittee on Health frequently sought common ground in an effort to balance innovation with the highest level of accuracy and reliability.

Andrew Fish, executive director of AdvaMed Diagnostics, explained the existing challenges surrounding the regulation of diagnostic tests: “The current diagnostics oversight paradigm results in a tremendous public health gap and highly disparate treatment of tests that are the same from the perspective of patient risk and safety, simply on the basis of whether they are developed by a manufacturer or a laboratory. This is bad public policy, provides an opportunity to use tests in clinical settings that have insufficient clinical data, and stifles investment in high quality products that are assured safe and effective for patients.”

Alan Mertz, president of the American Clinical Laboratory Association said that the documents released by FDA on July 31, 2014, go far beyond reflecting current Agency thinking, as they propose an entirely new regulatory framework that will be applied to clinical laboratories developing LDTs for the first time. If the FDA were to finalize this guidance, it would represent “nothing short of a wholesale reimagining of the regulation of laboratories, subjecting laboratories to an entirely new set of requirements that they have never faced before.”

Finally, Kathleen Wilsey, Co-Founder of Coalition for 21st Century Medicine added: “We are committed to working with FDA to strike the right balance between assuring public health and facilitating innovation in promulgating flexible regulations for all diagnostic tests—LDTs and IVDs. However, the Coalition is concerned that the proposed framework is incomplete, creates substantial uncertainty, and does not reflect a careful and important balance that recognizes the value and benefits that advanced diagnostics offer to patients, providers, and payers.”

FDA just released their Draft Guidance for Regulatory Oversight of LDTs. The Guidance indicates that FDA will rely on a “risk-based approach” to LDT oversight. The Agency will use the existing medical device classification system to evaluate the risk of the LDT and rely on input from industry experts to classify devices not previously classified by FDA.