Breakthroughs Blog: Pandemic preparedness

The health ministers of G20 nations concluded their annual meeting last weekend with the adoption of an “outcome document” that includes welcome commitments to advance the research and development (R&D) of health products. While normally such a ministerial-level meeting would end with the release of a formal consensus communique, broader geopolitics derailed this process, with Russia and China opposing the inclusion of language condemning the Russian war of aggression against Ukraine. Below we break down what R&D commitments are included in the outcome document, why it matters, and where conversations are expected to go from here. What’s in the declaration? At the highest level, G20 nations made commitments to strengthen the global health architecture and “build more resilient, equitable, sustainable and inclusive health systems equipped to address ongoing global health challenges and future public health emergencies with equitable access to safe, effective, quality-assured and affordable vaccines, therapeutics, diagnostics, and other medical countermeasures.” They also reaffirmed their commitment to ending the epidemics of AIDS, tuberculosis, and malaria; achieving polio eradication; advancing universal health coverage (UHC) and the Sustainable Development Goals (SDGs); and tackling antimicrobial resistance (AMR). On the latter issue of AMR, the ministers vowed to strengthen R&D for AMR and further the development of novel antimicrobials. They welcomed the work of various international initiatives and GHTC members including the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and the Global Antibiotic Research and Development Partnership (GARDP) and voiced continued support for the Global AMR R&D Hub, which was established under the German G20 presidency to promote AMR R&D coordination. On the broader issue of R&D for pandemic prevention, preparedness, and response (PPPR), G20 leaders agreed to support a World Health Organization (WHO)-led consultative process to develop an interim (and potentially later permanent) medical countermeasures (MCMs) mechanism to coordinate the end-to-end R&D, manufacturing, procurement, and equitable delivery of MCMs during health emergencies. They advised that such a mechanism should consider a “network of networks” approach, building off existing international and regional partnerships, and should be coherent with the outcomes of ongoing efforts to amend the International Health Regulations (IHR) and advance a binding pandemic instrument. Additionally, the ministers underscored the need to strengthen local and regional R&D networks and manufacturing capabilities, especially in low- and middle-income countries, as well as voiced support for what many call the “100 Days Mission” to develop and make available safe and effective vaccines, therapeutics, and diagnostics within 100 days of the identification of a pandemic or epidemic threat. They also noted the importance of public-private R&D partnerships—calling out the contributions of GHTC members the Coalition for Epidemic Preparedness Innovations (CEPI), Medicines Patent Pool (MPP), and FIND—and technology transfer and knowledge sharing “on voluntary and mutually agreed terms.”Why it matters?  G20 nations currently conduct and fund the majority of the world’s health R&D. Thus, it is great to see G20 leaders reaffirm the importance of R&D to achieving UHC, SDGs, and PPPR and demonstrate political will to accelerate R&D efforts. However, the outcome document is short on specifics as to how G20 countries intend to operationalize their many promises, and it disappointingly includes no new funding targets or commitments.  Additionally, going into this year’s G20 cycle, many observers and health advocates also expected that the G20 under the Indian presidency would play a more active role in envisioning and detailing a specific proposal for the creation of an end-to-end MCMs mechanism or platform to succeed and build upon the Access to COVID-19 Tools Accelerator. Instead, the G20 simply promised to support a WHO-led consultative process to design an interim mechanism and punted it to the International Negotiating Body (INB) process for a pandemic instrument to determine the prospects for a permanent MCMs platform. What’s next? With G20 nations offering few specifics on a vision to reimagine the global health architecture and advance an MCMs platform, the focal point for change is now squarely within the separate but interrelated processes now underway to amend the IHR, advance a pandemic accord that will create a more comprehensive framework for how countries will prevent and respond to outbreaks, and design an interim MCMs platform. While these processes have been ongoing, the deliberations have been stymied as countries struggle to reach consensus around thorny R&D topics like access and benefit sharing, with some pushing for more aggressive legally binding commitments for transparency, conditions on public R&D funding, patent waivers, and new supply chain mechanisms for ensuring low- and middle-income countries access to medical countermeasures. Questions remain on the full scope of some of the processes, and how they will delineate which issues will be tackled where and with the target date of May 2024 for the adoption of an instrument rapidly approaching and the INB and IHR processes largely behind schedule, it remains to be seen what tangible changes for R&D can be realized. While it is impossible to know what exactly what the future of these negotiations hold, GHTC promises to continue to watch, weigh in, and report back in the months ahead as these interrelated processes unfold. Stay tuned! 

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. As COVID-19 infections and hospitalizations rise across the United States, last week Moderna reported initial data that showed the efficacy of their updated COVID-19 vaccine, which was originally aimed at protecting against the XBB.1.5 subvariant, against the increasingly dominant Eris (EG.5) and Fornax (FL 1.5.1) subvariants. The updated vaccine is expected to be available in the fall, pending approvals from US Food and Drug Administration (FDA) and other national regulators. Novavax, as well as Pfizer and partner BioNTech, are also advancing updated shots.The United Kingdom’s Fleming Fund last week announced that it will provide up to $267.5 million for strengthening antimicrobial resistance (AMR) surveillance capacity in low- and middle-income countries in Africa and Asia, where the threat and burden of AMR is the highest. Specifically, the funding will go to upgrading laboratories, introducing new genome sequencing technology, and supporting training sessions. This announcement, which came ahead of this past weekend’s G20 Health Minister’s Meeting, where AMR was an important topic, marks a significant investment in a data-driven approach to fighting the rising threat of AMR.A new antibiotic combination drug that could significantly improve the treatment of complicated urinary tract infections and potentially serious infectious caused by highly resistant bacteria is now on track to receive a final review by FDA. Cefepime-taniborbactam, developed by Venatorx Pharmaceuticals and the Global Antibiotic Research & Development Partnership (GARDP), could be approved as early as next February. If successful, the treatment would be the first new treatment in GARDP’s clinical development portfolio to gain regulatory approval and would be a boon to global equitable access to new antibiotic treatments due to GARDP’s exclusive rights to distribute and sub-distribute the treatment in 64 low- and middle-income countries.

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. Duke University researchers have developed a synthetic antibiotic, LPC-233, that could be effective against drug-resistant superbugs and bacteria. LPC-233 was found to be effective in protecting mice from fatal doses of multidrug-resistant bacteria by disrupting the synthesis of the outer membrane of the bacteria. LPC-233, which is a synthetic compound of the LpxC inhibitor, was developed after the first human trial of LpxC inhibitors failed because of cardiovascular toxicity. Hopefully, future studies will confirm the new antibiotic as a potential tool to address drug-resistant superbugs.Last week, the Project to Accelerate New Treatments for Tuberculosis (PAN-TB) collaboration announced the start of a phase 2b/c clinical trial to evaluate novel treatment regimens for drug-sensitive tuberculosis (TB). The trial, which is sponsored by the Bill & Melinda Gates Foundation, will evaluate two novel drug regimens made up of different combinations of five antibacterial agents—including the TB Alliance-developed pretomanid and the Janssen-developed bedaquiline— and will take place in high-burden countries starting with South Africa. The results will hopefully lead to a new, shorter pan-TB treatment regimen for patients.The Coalition for Epidemic Preparedness Innovations (CEPI) and Gennova Biopharmaceuticals last week announced a new agreement to advance the development of Gennova’s self-amplifying mRNA platform to create vaccine candidates against unknown pathogenic threats with pandemic potential. The funding will support the optimization and production of the platform technology and then the production of a vaccine candidate for preclinical studies against a known virus, rabies, to assess the new technology. This will hopefully lead to the development of novel RNA vaccines, which could offer significant advantages over existing mRNA vaccine platform technologies.

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.