Although vaccine efforts against COVID-19 are moving at breakneck speed, experts caution that the 12- to 18-month time frame suggested by government officials is "overly optimistic." Therapeutics from antivirals and antibody cocktails to drugs focused on specific symptoms will act as a “bridge” while the world waits for a vaccine.
One of those approaches is well-known: convalescent plasma, or using the plasma of recovered patients to give others antibodies against a virus. It’s been used in various epidemics from measles and mumps to influenza. Today, Takeda, CSL Behring and an alliance of plasma specialists are working on a hyperimmune globulin, a purified version of this treatment, for COVID-19 infection.
“We know that passive immunotherapies work from historical experience,” said Chris Morabito, Ph.D., head of R&D for Takeda’s Plasma-Derived Therapies unit. “With coronaviruses, there is experience with SARS and MERS that hyperimmune approaches are effective, though none was developed for either disease because the disease stopped having pandemic potential before development could be completed.”
Hyperimmune globulins work by giving patients a mix of antibodies produced by different kinds of immune cells, so they have multiple different antibodies against multiple different antigens on the virus. Morabito called it a “shotgun approach” that could help patients fight off SARS-CoV-2, the virus that causes COVID-19, while researchers are still learning about the disease and how the virus interacts with the body.
The treatments are made by purifying antibodies from donated plasma, giving them some advantages over plain old convalescent plasma.
“[They are] a standard product, a drug produced from pooled plasma,” said Morabito, who authored a paper on the promise of plasma-based treatments against COVID-19. “We will know what the batch-to-batch consistency , what the neutralizing titer [of antibodies] is like. It’s a stable, homogeneous mixture, so we can give specific dosing instructions.”
Having worked on hyperimmune globulins against the H1N1 influenza pandemic in 2009, Takeda is confident it can quickly develop a treatment for COVID-19. Although vaccines are moving “very, very quickly,” Morabito reckons a hyperimmune treatment could come faster.
“It’s really accessible. In the pandemic, we are seeing the number of convalescent patients is increasing exponentially, as transmission was increasing exponentially,” he said. “With proper campaigning—which we have initiated—we should be able to get convalescent patients in to donate plasma and use that plasma for the production of the hyperimmune treatment.”
That’s part of why Takeda has teamed up with other plasma players as well as companies like Uber and Microsoft. It initially started work on its own program, TAK-888, but quickly realized it would need all the help it could get.
“We came to the conclusion quickly that at every step of the way we would need some help to mitigate the risks of developing this thing … The scale needed to do it quickly would require multiple partnerships. We abandoned the ghost and signed up with this coalition for plasma collection,” Morabito said..
The group, dubbed the CoVIg-19 Plasma Alliance, is pooling know-how and resources to develop a single, unbranded medicine. That includes collecting plasma, manufacturing the treatment and conducting clinical trials.
One potential hurdle is a “dearth of plasma” from which to produce the treatment. Over time, recovered patients will have fewer antibodies circulating in their blood as they’re no longer fighting infection.
“There will be a time coming in the next year—maybe sooner—at which collecting plasma from those particular convalescent patients will not produce a robust hyperimmune,” Morabito said.
“There is a limited period of time to work quickly to collect enough plasma to make this drug,” he added.
That said, Morabito thinks the group is working quickly enough that it won’t be an issue: “We do anticipate we will have the drug available before the end of the calendar year based on how well things are going with collections, manufacturing and the anticipated start of the clinical trial this summer,” he said.
The alliance will work with the National Institute of Allergy and Infectious Diseases to test the safety and efficacy of the treatment in adults with COVID-19. The global study will lay the groundwork for a regulatory submission for the treatment.