Breakthroughs Blog: Pandemic preparedness

Congressional negotiations are moving fast and furious as policymakers seek to reach an agreement to reauthorize must-pass legislation, known as the Pandemic and All-Hazards Preparedness Act (PAHPA), governing how the United States prepares for health threats. The latest 2019 reauthorization of the original 2006 law will expire on September 30, leaving legislators with a rapidly closing window to determine how national preparedness infrastructure should be reformed in the wake of the COVID-19 pandemic.Though this legislation has far-reaching implications for America’s entire preparedness architecture, most notably for global health research advocates, it authorizes the work of the Biomedical Advanced Research and Development Authority (BARDA), an agency charged with advancing the research and development (R&D) of medical countermeasures (MCMs) against health threats. BARDA was created via PAHPA in response to the 2001 anthrax attacks in the United States and in recognition of the need for the government to play a role in spurring R&D of tools for chemical, biological, radiological, and nuclear threats for which there is no commercial market. While historically, the agency has focused foremost on man-made bioterror threats, in the past decade, it has increasingly played a role in advancing vaccines, drugs, diagnostics, and other tools against naturally occurring global threats like Ebola, Zika, antimicrobial resistance (AMR), and COVID-19—for the latter, as one of the leaders of the US government’s Operation Warp Speed.While the COVID-19 pandemic underscored the unique value of BARDA’s R&D capabilities, it also brought the United States to a point of intense partisanship on issues of pandemic preparation and public health. These splits have plunged PAHPA—which has historically enjoyed an uncontroversial and bipartisan policymaking process—into a tense 2023 reauthorization cycle.Below we look at where negotiations stand in each chamber and where things could go from here.A bipartisan SenateOn the Senate side, the deliberations for a mostly clean reauthorization have gone relatively smoothly in the Health, Education, Labor, and Pensions (HELP) Committee. While an initial discussion draft released on July 3 reflected areas of disagreement between Chairman Bernie Sanders (I-VT)—who wanted to see the bill tackle drug pricing and supply chain challenges—and Ranking Member Bill Cassidy (R-LA) —who proposed changes to the priority review voucher (PRV) for MCMs—by the July 20 markup, the senators had worked out a bipartisan deal in the form of a managers amendment.The bill, which last week was approved to be reported out of committee, includes a comprise that would require drugmakers to alert the government of disruptions in the supply of drugs and pharmaceutical ingredients and a new government-directed study on policy solutions to delink drug prices from R&D costs in exchange for a straight five-year extension of the MCM PRV program. Importantly for global health research advocates, the bill also includes more expansive and explicit language directing BARDA to conduct R&D for known and as-yet-unknown pathogens with pandemic potential, as well as an amendment introduced by Sen. Hickenlooper (D-CO) to authorize the creation of a new US Food and Drug Administration (FDA) team tasked with reviewing MCMs for emerging pathogens—as was requested by FDA in their fiscal year 2024 priority letter. It is worth noting that the compromise forged between Sens. Sanders and Cassidy included new authorities for FDA that have been the cause of derision across the chamber on the House side.A partisan HouseIn the House, leading up to the Energy and Commerce (E&C) Committee’s July 19 markups, tensions remained heightened as Democrats and Republicans were still unable to reach bipartisan consensus on the two PAHPA bills introduced by Representative Richard Hudson (R-NC): H.R. 4421, the Preparing for All Hazards and Pathogens Reauthorization Act, which covers BARDA and its parent agency the Administration for Strategic Preparedness and Response (ASPR), and H.R. 4420, the Preparedness and Response Reauthorization Act, which proposes changes to the US Centers for Disease Control and Prevention (CDC). Rep. Hudson reportedly decided to split the House version of PAHPA into two bills to disentangle the more politicized portions of the bill, housed in H.R. 4420, from the ones with more consensus, housed in H.R. 4421.Both bills were approved last week to go to the floor of the House.Since the House’s preliminary June hearing on PAHPA at which Rep. Anna Eshoo (D-CA) announced that she had pulled her name from the legislation, Rep. Hudson’s PAHPA bills have advanced through the chamber on a purely partisan basis. Other vocal representatives, like E&C Committee Ranking Member Frank Pallone, Jr. (D-NJ), hammered Republicans for not including FDA authorities to address drug shortages in the scope of PAHPA. Unsatisfied with the Republicans’ response to their demands, House Democrats on the committee released their own version of PAHPA immediately before the July 19 markups. The Democrats’ draft bill includes provisions to strengthen CDC, increase funding for programs like the Strategic National Stockpile (SNS), and give FDA new authorities to mitigate drug shortages.This tension culminated in almost exclusively party-line votes approving 15 health policy-related bills that, among other provisions, would hamper CDC’s powers and, according to experts, underfund CDC, BARDA, SNS, and ASPR. In one small glimmer of good news, the Republican-led H.R. 4421 PAHPA bill, like its Senate counterpart, also included more expansive language directing BARDA’s research on emerging infectious diseases (EIDs).What now?For the first time, the House E&C Committee has sent PAHPA to the House floor on a partisan basis in striking contrast to the Senate HELP Committee’s mostly bipartisan process. Notably, House E&C Committee Chair Cathy McMorris Rodgers (R-WA) alluded to considering the Senate’s “more tailored approach to more FDA authorities” as a workable compromise, but only time will tell as the bills advance to the next stage in the process. If the current House and Senate versions of the bill receive the requisite votes to pass in each chamber, they will then be sent to the Conference Committee, where the differences must be reconciled, and the resulting bill will be sent back to the House and Senate floors for final votes.But with the partisan nature of the PAHPA bills in the House, the slim majority Republicans hold, and the difficult procedural hurdles in the Senate that have been used to hold up anything COVID-related, it could prove challenging for policymakers to reconcile around a bill capable of being passed in both chambers. The only sure thing is that this reauthorization process is unpredictable and at the whim of the current political climate.What is GHTC’s take?Earlier this year, GHTC put out a set of policy recommendations for the House and Senate to consider as they reauthorized PAHPA. Even though the process is not over, there are indications that some of our coalition’s priorities are represented in the draft bills from both the House and the Senate. As discussed, both bills contain explicit language highlighting the need for “advanced development and manufacturing of MCMs for viral families which have significant potential to cause a pandemic” and call out “emerging infectious diseases.” It is welcome news to see the bills specifically highlight the need for R&D for both known and as-yet-known, or Disease X, infectious disease threats.Additionally, the Hickenlooper amendment is also supported by GHTC since it would bolster FDA “activities to advance scientific research related to the development of tools, standards, and approaches to assess the safety, efficacy, quality, and performance of countermeasures.” The inclusion of both EID callouts and FDA’s fiscal year 2024 priorities are notable wins in a year marked by proposed funding cuts to global health programs.Of course, there are still areas of much-needed attention not fully addressed by the bills. The lack of boldness of either chambers’ bills can be attributed to the difficult fiscal environment Congress finds itself in—exemplified by the far more contentious appropriations bills that many believe are sending the United States on the path to a potential government shutdown. GHTC’s recommendations for Congress to create a dedicated EID funding line and authorize more money for AMR research at BARDA are not included in the bills—nor is there discussion on advancing the low-resource settings utility of BARDA products, inclusion of the Pioneering Antimicrobial Subscriptions To End Up surging Resistance (PASTEUR) Act to incentivize AMR research, or provisions to give BARDA loan authorities.However, through our staff-level conversations on the Hill, the dial seems to be turning in a positive direction for these priorities. Especially in discussions on EID funding and AMR priorities (including PASTEUR), there is growing bipartisan agreement that these issues are important enough for standalone funding—just not in this specific PAHPA during this particularly difficult fiscal year. Whether or not PAHPA is the vehicle, we see tremendous strides in the Hill’s recognition of the issues central to GHTC and our future advocacy.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Last week, the World Health Organization (WHO) prequalified the first conjugate vaccine to protect against the five dominant causes of meningococcal meningitis in Africa. The vaccine, MenFive, which was developed through a collaboration between the Serum Institute of India Private Limited and PATH, with financial support from the UK’s Foreign, Commonwealth, and Development Office, demonstrated a high level of safety and immunogenicity in extensive clinical studies in The Gambia, India, and Mali. WHO’s prequalification will allow MenFive to be procured by United Nations agencies and Gavi, offering a promising tool that could avert the annual outbreaks and epidemics in the African countries with the most meningitis cases and deaths.A multisite phase 1 HIV vaccine clinical trial carried out by the Globally Relevant AIDS Vaccine Europe-Africa Trials Partnership concluded with preliminary analysis demonstrating strong results. The novel mosaic HIV vaccine candidate, HIVconsvX, demonstrated the ability to trigger a strong and specific immune response that targets a broad range of HIV-1 variants, making it potentially applicable for HIV strains around the world. Researchers say it also represents an innovative approach within a pipeline of vaccine candidates that needs to be diverse to maximize the chances of success. The full reporting of the primary findings from the trial is expected later this year followed by further in-depth analysis.Last week, a joint statement from the United Nations Food and Agriculture Organization, WHO, and the World Organization for Animal Health warned that the H5N1 avian flu virus could adapt to more easily infect humans and urged multisector, international partnership and cooperation to protect both animal and human populations. The current H5N1 clade 2.3.4.4b has been circulating since 2020, causing unprecedented deaths around the world across different animal populations, especially in wild birds and increasingly, mammals. Although human cases have been only sporadic, maintaining and strengthening surveillance capability to be able to detect viral changes and human cases, as well as testing the currently circulating viruses for resistance to available antiviral drugs, will be essential to avoid further devastation.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Gavi, the World Health Organization (WHO), and UNICEF have announced that an initial 18 million doses of the world’s first malaria vaccine, RTS,S/AS01, will be rolled out in 12 African countries, where the risk of child illness and deaths from malaria is highest. The vaccine, which will be produced by GlaxoSmithKline and Bharat Biotech, is expected to arrive in the initial countries in late 2023. A further 16 countries have also asked for access and are expected to receive it once production has scaled up. Another malaria vaccine, R21, developed by Oxford University is currently awaiting WHO prequalification. In the coming years, both vaccines are expected to play a key role in the fight against malaria alongside other tools.A study published last week found that injections of broadly neutralizing antibodies in children living with HIV can improve the protective effects of antiretroviral drugs, marking the first time broadly neutralizing antibodies have been tested in combination with antiretroviral drugs in a pediatric population. The treatment suppressed cells that contained the virus and were capable of reactivating, paving the path to further research that could confirm the use of this method as a supplemental or alternative treatment for HIV in children. The publication of these findings follows recent research, which has focused on testing broadly neutralizing antibodies as a treatment for adults with HIV. Worldwide, about 1.7 million infants and children are living with HIV.Last week, Gavi confirmed that some of the $2.6 billion remaining in COVAX, the COVID-19 vaccine delivery initiative, could be redirected towards furthering investigational vaccine candidates for Marburg and Ebola Sudan, as well as a hexavalent vaccine that would offer protection against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and the inactivated polio vaccine. The investments for Marburg and Ebola Sudan will hopefully contribute to ensuring clinical trials in future outbreaks, especially after the scrapped trials during the recent Marburg and Ebola Sudan outbreaks.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Last week, the Bill & Melinda Gates Foundation and Wellcome Trust announced that they will jointly invest more than $500 million in phase 3 trials for the GSK-developed M72/AS01E tuberculosis (TB) vaccine, which could become the first new tuberculosis vaccine in 100 years. 2018 phase 2b trials showed that the vaccine was 50 percent effective, but after GSK pulled out because they did not see a commercial market for the vaccine, the company passed the license to the Bill & Melinda Gates Medical Research Institute in 2020. The phase 3 trials will involve 26,000 people in Africa and Southeast Asia, hopefully confirming the vaccine’s viability as TB cases and deaths rise around the world.A new initiative led by Gavi, the World Health Organization, and the Coalition for Epidemic Preparedness Innovations will work to stockpile experimental vaccines for infectious diseases with epidemic potential to improve preparedness for future outbreaks. This global virtual pooled inventory will initially focus on Marburg and the Sudan strain of Ebola, for which there are no existing vaccines or proven treatments. Last year’s outbreaks in Africa of these two hemorrhagic fevers saw aborted attempts to move forward clinical trials for vaccines, losing crucial opportunities to gather essential data on potential tools and highlighting the need for this kind of stockpiling, preparation, and partnership.The Medicines Patent Pool recently announced sublicensing agreements with seven manufacturers to produce and distribute generic versions of Shionogi’s COVID-19 antiviral treatment in low- and middle-income countries, improving availability and equitable access in these countries, even after the end of the Public Health Emergency of International Concern. The oral antiviral, Ensitrelvir, is currently only approved in Japan, although it is being considered in the United States and all 117 countries in the agreements. Medicines Patent Pool previously signed sublicensing agreements with Pfizer in 2021 to manufacture and distribute its treatment, Paxlovid, in 95 low- and middle-income countries.