Breakthroughs Blog: FDA

  Recently, there has been a surge of interest in evaluating progress made on the 2012 President’s Council of Advisors on Science and Technology’s (PCAST) recommendations that aim to accelerate research and development (R&D) of new therapeutics. Numerous policymakers and stakeholders have weighed in including contributors to the PCAST report and Dr. Janet Woodcock—director of the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER). PCAST’s recommendations—outlined in the Report to the President on Propelling Innovation in Drug Discovery, Development, and Evaluation—support an ambitious goal to double the output of new therapies for patients with unmet needs over the next 10-15 years.PCAST believes this goal can be achieved through several approaches and mechanisms including supporting federal funding for R&D, expanding use of public-private partnerships (PPPs), introducing new regulatory pathways, and improving capacity within the FDA to conduct post-marketing surveillance. The House Energy & Commerce Subcommittee on Health recently held a hearing to solicit expert testimony on PCAST’s recommendations and is seeking additional feedback on how PCAST’s recommendations have been implemented and can advance its 21st Century Cures Initiative. Launched in April, the 21st Century Cures Initiative is a bipartisan effort to bolster biomedical innovation and support the discovery, development, and delivery of new treatments. During the hearing, experts recognized Congress and the FDA’s expansion of expedited approval pathways for products that demonstrate health benefits early in their clinical development.   PCAST’s recommendations—outlined in the Report to the President on Propelling Innovation in Drug Discovery, Development, and Evaluation—support an ambitious goal to double the output of new therapies for patients with unmet needs over the next 10-15 years. Photo: PATH/Patrick McKern On the FDA Voice blog, Dr. Woodcock also outlined initiatives the FDA and Congress have undertaken that are aligned with PCAST’s recommendations. She notes that CDER is involved with many PPPs—which were funded by the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA)—which include collaborative efforts to advance knowledge of diseases and develop more efficient research tools and resources. The PCAST report specifically highlights the value of PPPs in R&D, noting the instrumental role they play in accelerating global health product development. By leveraging diverse expertise—including commercial knowledge and experience navigating regulatory pathways—PPPs facilitate the development of global health innovations. In addition to funding new PPPs, FDASIA also provided the groundwork for the Breakthrough Therapy designation—an expedited regulatory pathway for new drugs and biologics that demonstrate promising preliminary clinical evidence. Eligible products must treat serious or life-threatening diseases with unmet need. Products that receive Breakthrough Therapy designation benefit from a shortened development time period and intensive guidance from the FDA to guide them through the approval process. So far the FDA has granted Breakthrough Therapy designation to 44 products—including tafenoquine—an investigational medicine for the treatment and relapse prevention of Plasmodium vivax malaria. Tafenoquine was developed by GlaxoSmithKline and GHTC member Medicines for Malaria Venture. The expedited clinical development and review times for tafenoquine have the potential to accelerate downstream access to a much needed malaria drug. Breakthrough Therapy designation has been a welcome addition to the three other accelerated FDA pathways that existed when PCAST issued its recommendations. It is evident that PCAST’s recommendations have resulted in substantial initiatives that have enhanced R&D and global health innovation. Despite this progress, there are additional opportunities to strengthen US commitment to R&D and advance the discovery, development, and delivery of new therapeutics.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Yesterday, Senator Patty Murray (D-WA) introduced in the US Senate a significant piece of global health legislation that would strengthen global health research programming within the US Agency for International Development and improve coordination of global health research and development across the US government. The legislation—known as the 21st Century Global Health Technology Act—is companion legislation to the House version of the bill, HR 1515, which was introduced by Representatives Albio Sires (D-NJ) and Mario Diaz-Balart (R-FL) in April 2013. Knight Therapeutics—the developer of a new treatment for the parasitic disease leishmaniasis—is looking to be the first company to auction off the priority review voucher it received from the Food and Drug Administration (FDA). The company received this voucher—which it can redeem to have any drug moved to the front of FDA’s line for product review—following the approval of its leishmaniasis drug Impavido in late March. A Guardian article on the vaccine cold chain discusses the logistical challenges for the global health community in delivering and administering vaccines—which require constant refrigeration for efficacy—in environments with unreliable electricity and infrastructure. It calls for the next generation of vaccines to be developed with the goal of eliminating a burdensome cold chain and notes the success of the MenAfriVac™ vaccine for meningitis which can be used for up to four days outside the cold chain. During the World Health Assembly, UNITAID, the Drugs for Neglected Diseases initiative, and the Medicines Patent Pool launched a new initiative to develop and deliver improved treatments for children suffering from HIV and AIDS. The initiative–known as the Paediatric HIV Treatment Initiative (PHTI)–will focus on three areas: (1) research and development; (2) intellectual property; and (3) market-shaping to ensure availability of treatment regiments for children living with HIV and AIDS. The World Health Organization released a new document on its efforts to find innovative financing for neglected diseases. The documents states there is a $50 million budget line for demonstration projects and the Global Health R&D Observatory over four years, but did not make clear where the observatory would be situated.

As more detailed information about the President’s fiscal year (FY) 2015 budget requests to Congress is released, the results continue to be a mixed bag for global health research and development (R&D). The Congressional Budget Justifications—annual presentations to Congress to justify requests for funding—help shed a light into the administration’s priorities for FY 2015. National Institutes of Health (NIH) While the President made a modest request for overall NIH funding, the release of the NIH congressional budget justifications gives us a better sense of how the President hopes to fund specific institutes and programs at the agency. The National Institute of Infectious Diseases (NIAID) did include increases of $5.76 million for Biodefense and Emerging Infectious Diseases, $6.95 million for infectious and immunologic diseases, and $23.4 million for HIV and AIDS research compared with funding for FY 2014. The President’s request for the Office of AIDS Research—which covers all HIV and AIDS activities within all of the centers at NIH—was $3.004 billion. While this is nearly a $20 million increase from 2014 enacted levels, this number is still below enacted numbers for 2011 and 2012. Within this request was a decrease of 0.4 percent from 2014 funding for microbicides, an increase of 0.8 percent for vaccine research and a decrease of 1.4 percent for therapeutics research. Centers for Disease Control and Prevention (CDC) Historically, research at the CDC has led to major advances against devastating diseases, including the eradication of smallpox and advances in AIDS research. With a disappointing funding request for NIH, we were glad to see a much stronger request for the global health budget within the CDC. The President’s request included $445.29 million for Emerging and Zoonotic Infectious diseases, a $54.85 million increase from FY 2014 levels. Included in this was the $30 million requested for the Advanced Molecular Detection Initiative. The $30 million will go towards investments in advanced molecular detection technologies to help speed up outbreak detection and increase response efficacy. We’re glad to see the Administration acknowledging the need for the CDC to be cutting-edge in an increasingly global arena. US Food and Drug Administration (FDA) Amongst the government agencies involved in various stages of the development pipeline, the FDA has a vital role to play in accelerating the review of new global health products and strengthening the global regulatory system. Despite the tough budgetary times we currently face, Congress has been asking the FDA to do more with less. That said, we were pleased to see the President acknowledge that increased authority should also mean increased funding, with a robust request of $4.7 billion for the FDA, an 8.1 percent increase from Congress’ appropriation for 2014. The FDA’s Congressional Budget Justification acknowledged the unique role of the agency as an important international collaborator for global health through research and information sharing. The language specifically highlights the Biologics Program and its work to promote research and information sharing to facilitate access to vaccines and other products, harmonize regulatory standards, and establish and maintain standards for biologics. Another highlight is the news that FDA is in the process of drafting a proposed rule to add to their current list of neglected diseases for which they can allow accelerated reviews, and is specifically considering adding Chagas disease. US Agency for International Development (USAID) As we reported in our first blog post, while funding for global health at USAID and the Department of State was fairly disappointing, we were pleased to see an increase in the President’s request for malaria. Notable in this request was acknowledgement of the need for continued funding for R&D to support “the development of new malaria vaccine candidates, antimalarial drugs, new insecticides, and other malaria related research with multilateral donors.” Also in the USAID request was $153 million in central funding to accelerate science, technology innovation, and partnership. USAID describes this aim to “develop and scale breakthrough solutions and accelerate the transformation of the United States’ development enterprise by leveraging outside resources and improving the sustainability of development programs by attracting private-sector, market driven resources.” Department of Defense (DoD) DoD is the only US agency that funds global health research and product development from discovery to introduction. While we’re still sifting through all of the details in the Defense budget justifications, R&D at the agency—including health R&D—increased overall by 1.7 percent over FY 2014 enacted levels. Much of the global health research at DoD is funded through the Army’s Research, Development Testing and Evaluation (RDT&E) division as well as the Defense Health Program—including research on HIV and AIDS, malaria, and leishmaniasis. While we’re grateful the administration is continuing to recognize the need for sustained, robust support for global health R&D across several agencies, the decline of global health research funding in some key accounts remains concerning. We’ll look to Congress to equip these agencies with the necessary resources to carry out their essential role in developing new global health tools.

Yesterday, the White House released President Obama’s much-anticipated budget request for fiscal year (FY) 2015. After hearing that the budget would be released in two phases, we weren’t sure what level of detail or clarity to expect from the top-line numbers. As it turns out, the message is murky—for now. Below are some initial takeaways on the budget proposal’s impact on global health research and development (R&D). State and USAID Global Health Programs While funding for the overall 150 international affairs account remained fairly stagnant compared with FY 2014, funding for the State Department’s global health programs—which fund most global health R&D at the US Agency for International Development (USAID) and the State Department—took a concerning downward shift, falling by 4.6 percent overall. The Maternal & Child Health, Tuberculosis, and Global HIV and AIDS programs that fund research for many new global health tools all saw decreases to varying degrees when compared with the levels that Congress just approved for them in its FY 2014 budget agreement. There were a few ‘winners’—a relative term only; USAID’s Malaria and Family Planning programs saw small increases, and GAVI—which works to scale up currently available vaccines—saw its request increased by $25 million over FY 2014. As many in the community have voiced, the flat-funding of the President’s Emergency Plan for AIDS Relief—coupled with a possible $300 million decrease in the US’s contribution to the Global Fund to Fight AIDS, Tuberculosis, and Malaria—is disappointing, if not unexpected. Funding for the State Department’s global health programs—which fund most global health R&D at the US Agency for International Development (USAID) and the State Department—took a concerning downward shift, falling by 4.6 percent overall. Although these cuts are concerning, the President’s budget request did indicate that the administration is aware of the need for sustained global health R&D programming and recognized the important role that USAID plays in fostering innovation. The President requested $146.3 million for the new Global Development Lab at USAID, which “will consolidate and expand USAID's efforts in science, technology, innovation and partnerships, creating a world-class capability to discover, incubate, test, and scale transformational solutions to the greatest development challenges that we face today.” However, according to the budget justification text, only about $5 million of this funding will go to global health programs.   Global Health R&D at NIH, CDC and FDA The President requested $30.2 billion for funding at the National Institutes of Health (NIH), a slight increase from 2014 appropriations levels of $29.9 billion, but still lower than the President’s request for FY 2014—continuing a troubling decline. It is estimated that NIH’s funding has decreased 15 percent since FY 2004. Within the NIH, the National Institute of Allergy and Infectious Diseases was funded at $4.423 billion, a 3.4 percent decrease from the President’s request for 2014, but a slight increase from the 2014 appropriated budget of $4.359 billion. The National Center for Advancing Translational Science saw a slight cut from FY 2014 appropriations and previous requests, while the National Institute of Child Health and Human Development and the Fogarty International Center were essentially flat-funded. There was potentially better news for global health R&D funding at the Centers for Disease Control and Prevention (CDC). The President requested a total of $464 million for CDC’s Center for Global Health—a significant increase over FY 2014. CDC’s Center for Emerging Zoonotic and Infectious Diseases also received a welcome increase. Both of these CDC centers are involved in the new Global Health Security Agenda programming. While the budget text says that the President requested $45 million for the new initiative, it’s not yet clear where this funding will come from. In more positive news, the President also requested just over $4.7 billion for the US Food and Drug Administration (FDA), allaying fears that the strong FY 2014 funding ($4.3 billion) would not be continued. The funding also assumes $2.612 billion in user fee income. Opportunity, Growth and Security Initiative Adding to the opaque nature of several parts of the global health and science accounts within the President’s budget request is the new $56 billion Opportunity, Growth and Security Initiative. Funds in this category include the $300 million that would go to the Global Fund if other nations are able to increase their own commitments, as well as other funding that would go to NIH and the Science, Technology, Innovation and Partnerships (STIP) in Development program via the new Global Development Lab at USAID. It’s still unclear whether this money will be allocated as stated, and many in the global health community are concerned that it would draw funds away from other health-related programs that have already been flat-funded or seen cuts. While we’re still waiting for more figures for NIH and the Department of Defense’s global health R&D programs, and details from additional budget justification documents—it’s clear that Congress has its work cut out for it in protecting global health R&D programming across the US government. When the appropriations committees from the House and Senate develop their own proposals later this spring, they should work to sustain and protect global health research and product development at USAID, CDC, NIH, FDA and the Defense Department in order to keep up the fight against global health diseases.