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Warp Speed accelerating mAbs, bullish on convalescent plasma for COVID-19

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The U.S. government is accelerating the development of two forms of passive immunity for COVID-19 -- mAbs and convalescent plasma -- as well as antiviral, immune-modulating and anticoagulation agents, Janet Woodcock and a senior government official said Monday.

Although Operation Warp Speed is accelerating vaccine development, it is also prioritizing therapeutics because they could be ready for deployment more quickly, and because they will be needed to fill gaps caused by vaccines that are not 100% protective and from incomplete vaccination levels.

“While we think it is fair to say that vaccine progress is occurring at warp speed, a pace faster than any vaccines have been developed in history, therapeutics are even faster and we believe we will have new options for saving American lives as soon as the early fall,” a senior administration official who declined to be identified, said.

Agents that provide passive immunity may be among the first wave of new therapies, said Woodcock, who has temporarily stepped away from her position as director of FDA’s Center for Drug Evaluation and Research to head Operation Warp Speed’s therapeutics team.

The Trump administration is gearing up a publicity campaign to persuade recovered COVID-19 patients to donate convalescent plasma. Enthusiasm for the therapy, however, is based on anecdotal evidence, not robust clinical data.

In contrast, mAbs are being developed rigorously in randomized trials.

Master protocols for mAbs

Operation Warp Speed is supporting two master protocols for mAbs and is preparing a public campaign to solicit plasma donations from individuals who have recently recovered from COVID-19.

Phase II to III Bayesian master protocols of outpatient and hospitalized COVID-19 could start this month, Woodcock said. The protocols have been developed in collaboration with Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership led by NIH, Woodcock said. They will test single antibodies, cocktails and polyclonal antibodies, and could potentially also include antiviral agents, she said.

The master protocols will include several doses but will not be set up to do full dose-ranging comparisons. Sponsors will be expected to conduct Phase I and early Phase II dose-ranging trials prior to enrollment of their candidate therapies in the master protocols, Woodcock said.

“The readouts from these will depend on the speed of enrollment, and of course the size of the treatment effect,” she added. “We hope to have some info by early fall.”

Antibody therapies are “very promising across the many of the stages of the disease, particularly the earlier stage,” Woodcock said.

Warp Speed is aware of about 50 mAb programs for COVID-19, she said.

If they are demonstrated to be safe and effective, limitations on manufacturing capacity will mean that supplies of mAbs are unlikely to come close to meeting demand (see “The Critical Path to COVID-19 Therapies”).

Convalescent plasma

Woodcock expressed enthusiasm for convalescent plasma, although she acknowledged that “we still don’t know for sure if it works” for COVID-19.

Although the Trump administration has expressed optimism about convalescent plasma, there is little data to support use of the therapy.

While there are no data from randomized, controlled trials, there is a “strong possibility” convalescent plasma is effective based on the presence of antibodies, Woodcock said.

Americans have received about 40,000 units of convalescent plasma under an expanded access program sponsored by Biomedical Advanced Research and Development Authority (BARDA) and run by the Mayo Clinic.

“In the absence of randomized controlled trials, a very large treatment effect would be required to detect benefits of convalescent plasma,” Luciana Borio, former acting FDA chief scientist, told BioCentury. “There is no evidence thus far of benefit, other than anecdotal reports which are inherently unreliable.”

A recent randomized trial in Denmark was halted prematurely when investigators realized that most patients already had high levels of neutralizing antibodies at baseline.

To be beneficial, convalescent plasma would “likely have to be administered very early, perhaps as post-exposure prophylaxis,” Borio said. “In that case, the safety-benefit profile needs to be established through randomized, controlled trials. Even then, mAbs that are highly potent and standardized would likely be a better option.”

Despite the lack of firm evidence supporting its use, the Trump administration is gearing up for to dramatically increase collection and use of convalescent plasma. Woodcock urged reporters to help with the initiative by informing recovered COVID-19 patients that they can donate plasma.

“There are blood drives ongoing, and the U.S. government will be trying to accelerate these drives for convalescent plasma,” she said. “Donors need to be able to identify that they’re eligible and that they can help someone else.”

Because antibody levels decline quickly, donations must be provided within about a month of a patient’s recovery from COVID-19, Woodcock said.

Antiviral, immune-modulation, anticoagulation

In addition to passive immunity, Warp Speed is working with ACTIV and NIH to accelerate the development of antivirals, immune-modulators and anticoagulants. Some of the trials which were slated to begin in late June will start this month (see “ACTIV Coming Into Focus”).

Because it aims to develop therapeutic options that can authorized and manufactured at scale this year, the initiative is focusing on repurposed antivirals and those that have undergone extremely rapid preclinical development, Woodcock said.

Warp Speed is also accelerating the development of immune-modulators that can address ADRS and the cytokine storm that characterize late-stage COVID-19 in hospitalize patients, she said.

In addition, it is working with NIH’s National Heart, Lung, and Blood Institute on trials of therapies to address coagulation that causes strokes and deaths in COVID-19 patients.

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