Vaccines aren’t enough: COVID R&D’s adaptive platform trial aims to fill the need for new therapies
Pharma peers joined forces to create an adaptive platform study for COVID-19
The need for therapies for hospitalized patients will persist for years, and the COVID R&D Alliance’s COMMUNITY study is designed to address it.
The COVID R&D Alliance is looking beyond the imminent rollout of vaccines, anticipating an ongoing need for effective therapies in hospitalized COVID-19 patients. Last week, it launched the COMMUNITY adaptive platform trial to foster their development.
The COVID R&D group came together early in the pandemic as a precompetitive group of pharmas, biotechs and VCs, and announced last week one achievement of the year-long effort with the COMMUNITY trial, designed to evaluate multiple therapies in parallel across the spectrum of hospitalized COVID-19 patients.
In addition to breaking boundaries of competitors working together, the COMMUNITY study represents a rare example of pharma companies sponsoring a large adaptive platform study — a step toward accelerating drug development that BioCentury called for in this year’s Back to School essay.
Amgen Inc. (NASDAQ:AMGN) is sponsoring the study, which is kicking off with three immunomodulators from consortia members — Otezla apremilast from Amgen, Takhzyro lanadelumab from Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK), and zilucoplan from UCB Group.
The consortium plans to continue adding new therapies including antivirals and vascular agents.
Otezla entered the study last week, and the other two therapies are expected to enter in the coming weeks.
At least 13 master platform trials for COVID-19 are in progress, and they have produced some of the most actionable data on therapeutics to date.
Adaptive platform trials test multiple therapies under the same overarching structure with a shared control arm. The benefits include fewer patients receiving placebo or standard of care, and the potential for faster answers on efficacy due to the use of Bayesian statistics to allocate patients to treatment arms.
COVID R&D has worked closely with other adaptive platform trials this year including the I-SPY COVID-19 study and NIH’s ACTIV trials.
Andy Plump, president of R&D at Takeda, said in this case, more was better.
“This wasn’t a mutually exclusive decision to create our own platform trial. The group worked closely with a number of platform studies, but we realized there was still a gap, and having another study to complement those was a necessity,” Plump told BioCentury.
The group aims to address the lack of treatments for hospitalized patients with disease ranging from moderate to severe.
“There’s not enough substrate to study all of the repurposed and novel drugs that meet the bar. We just couldn’t fit all the drugs into existing studies,” Plump added.
Elliott Levy, SVP of global development at Amgen, added: “In the alliance, we believe there’s a need for more than one adaptive platform trial. There’s a need for a network of these trials to support the rapid development of evidence around as broad a range of therapeutics as possible.”
He told BioCentury that COMMUNITY is differentiated from the other studies because it’s designed to enroll a broad range of hospitalized patients, evaluate a large number of therapies in parallel and will do so in a fully blinded and placebo-controlled structure.
“There’s not enough substrate to study all of the repurposed and novel drugs that meet the bar. We just couldn’t fit all the drugs into existing studies.”
Although the COMMUNITY trial is later to the game than the other platforms, Levy said the drug development priorities haven’t shifted since the beginning of the pandemic. He also said the trial is designed to identify treatments for unmet needs that will persist even after vaccines and mAbs are more widely available.
“Efficacy of the first vaccines is really more than I think anyone had dreamed of, and clearly if those vaccines were to be administered to essentially every person in the world, COVID-19 would probably cease to be a clinical problem, but unfortunately that’s not likely,” he said.
Levy added that data for the mAbs is more compelling when used early in the course of disease, and “there will continue to be a need for therapy for patients who become sick enough for hospitalization.”
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and the partners Eli Lilly and Co. (NYSE:LLY) and AbCellera Biologics Inc. received emergency use authorization for their respective mAb cocktails in November.
The COMMUNITY study is starting with immunomodulators that impact the vasculature, and is pursuing mechanisms that haven’t been tested in randomized controlled studies in COVID-19 patients before.
“We will capitalize on those lessons learned and would do what we’ve done through the alliance in the next pandemic, but faster and better.”
Plump told BioCentury that Takhzyro affects the kallikrein system, a sequence of proteases that lead to the development of bradykinin peptides. Bradykinins have been shown to cause vascular leakage and inflammation.
“We believe this virus has created an exaggerated response of this system that leads to a number of adverse effects. We’re not talking about testing a steroid or a TNF or an IL-6. We’re talking about a unique biological pathway that has never been tested in this disease,” he added.
UCB’s zilucoplan is a macrocyclic peptide that disrupts the complement cascade.
Although the first three therapies were contributed by consortium members, Plump said future molecules can come from anywhere.
The COMMUNITY study isn’t designed to continue after it meets its requirements for this pandemic, but Levy and Plump agree the concept and learnings from organizing the study can be applied to future pandemics and other diseases. The consortium does not have plans to do that yet.
The focus needs to be on collaborating around adaptive platform studies, they agree, which saw very little uptake outside cancer prior to the pandemic.
“This is 100% a paradigm we need to figure out. We’re fierce competitors, but first and foremost, we want to do the right thing and I believe across the board we have an incredible group of individuals. Now we have to start dissecting what truly drives competition in business and what’s really precompetitive,” Plump said.
“Is running a trial with multiple active arms competitive? I think so, we just don’t like doing that. We don’t like putting faith in another company to run the trial. We don’t like to go head-to-head,” he said.
But Plump added that the competitors need to find a way to come together to organize these types of trials, to both prepare for future pandemics and identify more efficient ways to conduct drug development in general.
“We don’t have any plans yet for a future pandemic, but there have been important learnings from the COVID R&D Alliance and the COMMUNITY trial that apply. We’ve learned the value of collaboration between industry peers in solving difficult public health problems, we’ve been successful in promoting data sharing of both real-world and clinical evidence and in pooling analytical resources to derive insights from evidence,” Levy added.
“My expectation is that we will capitalize on those lessons learned and would do what we’ve done through the alliance in the next pandemic, but faster and better,” he added.
Levy noted that members of the alliance are questioning whether industry should consider “standing up a trial that could be kept warm during interpandemic periods and repurposed when needed,” much like REMAP-CAP.
Plump added that beyond pandemics, the collaborative adaptive trial structure could be applied to any disease. Alzheimer’s disease is a priority due to the length of the trials and small effect sizes, he said.
PDE-4 – Phosphodiesterase-4