FDA, Sponsors Seek New Models for Drug Development in the Year Ahead

The shift to personalized medicine has begun to account for a greater portion of new therapies in pharmaceutical pipelines, and the biomedical research community is watching to see if this trend continues in the coming months. Access to genomic data and more effective diagnostics support development of treatments for specific patient populations with serious conditions. Orphan drugs now account for a significant portion of new drugs approved by the Food and Drug Administration, with Big Pharma joining small biotechs in exploring these new markets.

FDA is encouraging these innovations with special programs to speed development and approval of  “breakthrough” therapies that offer a significant improvement over existing treatments. “Breakthroughs are breaking out,” commented John Jenkins, director of the Office of New Drugs in the Center for Drug Evaluation and Research (CDER), at the FDA/CMS Summit in December. He noted the unanticipated success of the program, with 34 breakthrough designations granted (of 113 requests) during the past year. That has led to approval of three new breakthrough drugs in the program’s first year.

Despite these gains, overall new drug approvals declined in 2013 from the near-record 39 new molecular entities (NMEs) of the previous year. FDA had approved only 26 NMEs as of early December 2013, Jenkins reported. He insisted that there is no slow-down in the review process, but that fewer new drug applications were filed. Approvals for NMEs “plateaued out” this year, Jenkins said, explaining that 39 new drugs is not the “new normal.” FDA has averaged around 33-35 new drug approvals per year for the past decade, and he expects that range to hold.

Another sign that CDER is not more risk averse, said Jenkins, is that it has achieved a high first-cycle approval rate, a main goal of the current user fee program, which extended review timeframes by two months for this purpose. Moreover, FDA is meeting goals for timely review of all priority applications, and almost three-fourths of novel drugs are first approved in the U.S., Jenkins noted.

A more transparent NDA review program, he added, helps sponsors remedy shortcomings and rescue troubled applications more quickly. Through meetings and more regular communications with company staffs, FDA is able to provide information on the status of an application and apparent gaps in submitted data, enabling sponsors to start planning for additional clinical trials even before they get a complete response letter. At the same time, Jenkins noted a decrease in the number of applications that are resubmitted, a development that he believes reflects changing company business decisions.

While the shift to more targeted drugs is exciting, it also raises concerns about reduced investment in new medicines to treat major diseases, such as diabetes and cardiovascular conditions that affect millions. “Having more choice is good,” Jenkins commented, urging another look at “me-too” drugs. He noted that the first-in-class drug is not always the best and that the focus on patient sub-groups may drive investment away from important innovation.  If more new members of a drug class are not developed, he noted, some “real innovation” is in danger of being left by the wayside.

More resources needed
A large cloud hanging over these gains in drug development and approval is the continued squeeze on FDA funding. While the breakthrough drug program has been a notable success, Congress provided no additional resources to support all the time-consuming advisory functions and accelerated review for the promising new therapies that are emerging, Jenkins noted. He expressed frustration over budget cuts and sequestration, which has siphoned off a portion of already-paid user fees.

FDA commissioner Margaret Hamburg made similar comments at the December summit. While praising Congress for providing added authorities needed by FDA to tackle serious drug safety issues -- namely drug compounding, supply chain security and drug shortages -- Hamburg  urged Congress to provide “the kind of real resources” that are needed for FDA to meet these greater challenges.

One strategy for bolstering biopharma R&D involves forming new partnerships to fill resource gaps. The drop in federal funding for FDA and for the National Institutes of Health, along with declining revenues at industry leaders, is spurring more collaboration across the biomedical research enterprise. Three top cancer research institutes recently formed an innovative joint venture. Pharma companies are negotiating research agreements with biotech firms, instead of just buying them. Public-private partnership seek to establish standards, harmonize electronic data systems and utilize new models for protocol design.

These initiatives speak to the need to streamline research operations and testing requirements. Debate continues over appropriate use of biomarkers and endpoints in clinical trials and more innovative analytical methods and study designs. Progress in these areas promises to establish a more efficient and effective clinical research system, which is key to producing less costly new medicines that are more accessible to patients. Yet concerns about patient privacy and safety continue to complicate changes in research rules and policies. A number of federal panels and commissions are examining opportunities for achieving efficiencies, generating some optimism that positive gains may gain traction in coming months.