The NIH says its month-old public-private partnership bringing together biopharmas with U.S. and international regulators has taken its first steps to accelerate development of drugs and vaccines against COVID-19.
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) has identified four priorities in its effort to develop an international strategy for quickly developing therapeutics against the virus:
- Develop a collaborative, streamlined forum to identify preclinical treatments
- Accelerate clinical testing of the most promising vaccines and treatments
- Improve clinical trial capacity and effectiveness
- Accelerate the evaluation of vaccine candidates to enable rapid authorization or approval
Each priority is the focus of a working group created to address its assigned goal.
“To address what may be the greatest public health crisis of this generation, it is imperative that all sectors of society work together in unprecedented ways, with unprecedented speed,” NIH director Francis S. Collins, MD, PhD, and Paul Stoffels, MD, vice chairman of the executive committee and CSO, Johnson & Johnson (J&J), wrote in “Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): An Unprecedented Partnership for Unprecedented Times,” a commentary published Monday in JAMA.
The main goals of ACTIV, according to Collins and Stoffels, “are to establish a collaborative framework for prioritizing vaccine and therapeutic candidates, to streamline clinical trials and tap into existing clinical trial networks, and to coordinate regulatory processes and leverage assets among all partners.”
Those partners include 18 biopharmas, up from 16 when ACTIV was first announced on April 17. Eisai and Gilead Sciences have joined a group of participating companies that included J&J and many other global biopharmas: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec, GlaxoSmithKline (GSK), KSQ Therapeutics, Merck & Co., Novartis, Pfizer, Roche and its Genentech subsidiary, Sanofi, Takeda Pharmaceutical, and Vir Biotechnology.
Also members of ACTIV are the European Medicines Agency, the NIH, and six other U.S. government agencies: the Biomedical Advanced Research and Development Authority (BARDA), Centers for Disease Control and Prevention (CDC), the Department of Defense, the Department of Veterans Affairs, and the FDA.
The regulators and companies were brought together with academic experts by NIH, coordinated by the Foundation for the National Institutes of Health (FNIH) on April 3.
“In the United States, there was no true overarching national process in either the public or private sector to prioritize candidate therapeutic agents or vaccines, and no efforts were underway to develop a clear inventory of clinical trial capacity that could be brought to bear on this public health emergency,” Collins and Stoffels wrote, explaining how ACTIV came about. “Many key factors had to change if COVID-19 was to be addressed effectively in a relatively short time frame.”
Collins and Stoffels outlined efforts by the working groups to achieve those goals.
ACTIV’s Preclinical Working Group was formed to standardize and share preclinical evaluation resources and methods and accelerate testing of candidate therapies and vaccines to support entry into clinical trials: “The aim is to increase access to validated animal models and to enhance comparison of approaches to identify informative assays,” the co-authors wrote.
Through ACTIV, the working group is expected to extend preclinical researchers’ access to high-throughput screening systems, especially those within Biosafety Level 3 (BSL3) facilities currently required for many SARS-CoV-2 studies. The group also is defining an approach for prioritizing animal use, assay selection, and staging of testing, as well as completing an inventory of animal models, assays, and BSL3 and BSL4 facilities.
The Therapeutics Clinical Working Group has the task of prioritizing and accelerating clinical evaluation of a long list of therapeutic candidates for COVID-19 with near-term potential. Priority will be given to candidates that have already entered human clinical trials—such as agents with either direct-acting or host-directed antiviral activity, including immunomodulators, severe symptom modulators, neutralizing antibodies, or vaccines. The group plans to set criteria for evaluating and ranking potential candidate therapies submitted by industry partners through a steering committee whose members possess expertise and a commitment to objectivity.
Six potential candidates
On May 6, the Therapeutics Clinical Working Group presented its first list of repurposed agents recommended for inclusion in ACTIV’s master protocol for adaptive clinical trials. Of 39 agents that underwent final review, the group identified six candidate agents—identified only as immunomodulators and supportive therapies—that it proposes to advance into one or more master protocol clinical trials, expected to begin later in May.
The Clinical Trial Capacity Working Group is charged with assembling and coordinating existing networks of clinical trials, with the objectives of increasing efficiency and building capacity. The group plans to develop an inventory of clinical trial networks supported by NIH and other public and private funders, including contract research organizations. The working group will identify for each network their specialization in different populations and disease stages, and establish a mechanism for coordinating across networks with the aims of speeding up trials, tracking incidence across sites, and projecting future capacity.
The clinical trials inventory subgroup has identified 44 networks for potential inclusion in COVID-19 trials, Collins and Stoffels said. Meanwhile, the survey subgroup has developed two surveys designed to evaluate the capabilities and capacities of those networks, while an innovation subgroup has developed a matrix to guide deployment of innovative solutions throughout the trial life cycle.
ACTIV’s Vaccines Working Group aims to accelerate evaluation of vaccine candidates to enable rapid authorization or approval. The work will include developing a harmonized master protocol for adaptive trials of multiple vaccines, as well as development of a trial network that could enroll as many as 100,000 volunteers in areas where COVID-19 is actively circulating. The group also aims to identify biomarkers to speed authorization or approval and to provide evidence to address immune enhancement and other safety concerns.
The working group plans to assess multiple vaccine candidates, with the most promising to be advanced into a Phase II/III adaptive trial platform using large geographic networks in and outside the U.S. ACTIV said it intends to have vaccine candidates ready to enter clinical trials by July 1.
According to Collins and Stoffels, ACTIV came together much faster than another public-private effort, the Accelerating Medicines Partnership (AMP), which took about two years from concept to launch.
[This report has been updated to remove Karuna Therapeutics from the group of companies that have joined ACTIV, after Karuna told GEN it was erroneously included among participating biopharmas on the program’s page within the NIH website, and had requested that the agency remove it from the page].