The goal is to tamp down an out-of-control immune response that seems to cause many deaths
Researchers are investigating whether a common blood-plasma product used in treating immune-system disorders could also be effective in coronavirus patients and potentially shape future trials of new treatments specific to Covid-19.
Already, some industry experts have raised concerns that new demand for the product, intravenous immunoglobulin, or IVIG, for experimental treatment of Covid-19 patients could lead to shortages for patients with conditions for whom the benefit is proven.
The immunoglobulin the researchers are focused on is made from antibodies taken from the blood plasma of donors in the general population. These antibodies aren’t expected to specifically target the coronavirus, because there isn’t yet widespread immunity to it.
The antibodies are believed to help regulate the immune system overall, though, and researchers hope they can tamp down the out-of-control immune response that appears to be the cause of death in many coronavirus patients.
Some physicians and researchers have given IVIG to Covid-19 patients experimentally, but it doesn’t appear to be in widespread use for that purpose.
Studies of how Covid-19 patients respond to IVIG could eventually help inform drug companies’ efforts to develop a new product using the plasma of recently recovered patients, which would contain antibodies specific to the coronavirus.
If proved effective, standard IVIG could offer an immediate new treatment option, because it is already in stock in many hospitals.
“We want to help now and see what we could do with the product that is readily available,” said Flemming Nielsen, president of the U.S. subsidiary of Switzerland-based Octapharma AG, which is studying whether IVIG can help Covid-19 patients. The company is also working with other manufacturers to make coronavirus-specific immunoglobulin.
One theory is that antibodies regulate immune response by binding to immune cells and stopping them from releasing cytokines, proteins that help fight infection but that in excess can lead to organ failure and death.
There is no guarantee off-the-shelf IVIG will be effective for treating Covid-19. Experts caution that it isn’t always clear how the therapy works, even in some diseases for which it is routinely used.
Immunoglobulin is a versatile medicine used for patients with certain autoimmune disorders as well as rare diseases such as primary immunodeficiency, for whom the antibodies help fight everyday infections.
Last year, some hospitals and clinics had difficulties getting immunoglobulin due to increased demand and manufacturing issues. The supply of regular plasma is expected to fall because donors are staying at home to stop the spread of the coronavirus.
“We are just starting to recover from the shortage and this hit,” said Michelle Vogel, vice president of patient advocacy for CSI Pharmacy, a specialty pharmacy.
Similar concerns arose last month when interest surged in the malaria drugs hydroxychloroquine and chloroquine as possible Covid-19 treatments. That led to hoarding and shortages for patients who rely on the drugs for conditions including lupus and rheumatoid arthritis. The Food and Drug Administration has since warned against their use for coronavirus patients outside of clinical trials.
Chris Goodnow, an immunologist and executive director at the Garvan Institute of Medical Research in Australia, said the idea that IVIG could help Covid-19 patients is still very hypothetical. “The fundamental Hippocratic oath is do no harm,” he said. “Creating a scarcity for a drug does harm.”
Australia-based CSL Ltd., one of the biggest plasma companies globally, is focusing on developing a Covid-specific product, Chief Medical Officer Charmaine Gittleson said. At this point, CSL’s preference is that off-the-shelf immunoglobulin be given to patients who need it to treat chronic illness, she said. “For many of these patients, there aren’t any alternatives.”
Stanley Jordan, director of nephrology and transplant immunology at Cedars-Sinai Medical Center in Los Angeles, said IVIG is “a bread-and-butter medicine” in treating many conditions.
“There are a lot of potential ways IVIG can work to block inflammation. I don’t know if that is solid enough to be something you want to pull off the shelf for Covid patients,” he said.
It makes more sense to create and test a product from recovered patients instead, he said.
Early reports of the use of IVIG to treat Covid-19 patients in China sparked interest in further studies. Researchers at Peking Union Medical College Hospital, in Beijing, reported successfully using high-dose IVIG in three severely ill patients.
A randomized controlled clinical trial evaluating whether high-dose IVIG is effective in severely ill Covid-19 patients is under way, they added.
A larger study looking at electronic medical records of patients at eight treatment centers in China showed benefit only in a small group of critically ill Covid-19 patients who got a high dose soon after their admission to the hospital. The studies haven’t been peer-reviewed, and researchers in them couldn’t be reached for comment.
Other research is planned in the U.S. and Europe. Octapharma is supporting a study of 20 patients at Sharp HealthCare hospitals in the San Diego area after being approached by a doctor there, George Sakoulas.
The study would include patients who require significant oxygen but don’t yet need a ventilator. Half the patients, randomly selected, would receive immunoglobulin; the other half would receive the typical standard of care but not immunoglobulin. Investigators will know which patients are in each group.
The study could quickly generate data that could then be used to construct larger studies, said Huub Kreuwel, vice president of medical affairs at Octapharma’s U.S. unit. He said the company is organizing a future study of about 60 patients that would be randomized, controlled and double-blind, meaning investigators wouldn’t know which patients were in each group.
Dr. Sakoulas said he wanted to investigate IVIG further after treating a 62-year-old Covid-19 patient who had hypertension and diabetes and had previously received chemotherapy. She was getting oxygen but wasn’t on a ventilator. Within 72 hours of the immunoglobulin treatment, her fever had broken and she was breathing normally without oxygen.
Dr. Sakoulas said he has previously given IVIG to patients with complications from the flu, who recovered.
At Grifols SA, a large Spain-based maker of pharmaceuticals and chemicals, preliminary data show that antibodies in the company’s IVIG products could bind to the coronavirus, suggesting its existing products might help people with Covid-19. The data wasn’t published in a peer-reviewed journal, and the company hopes to study the idea further in a pilot trial in Spain.
Doctors at Sainte-Anne Hospital in Paris are organizing a randomized, controlled, double-blind study to investigate if IVIG can help Covid-19 patients. They initially planned to recruit about 140 patients already on mechanical ventilation, though the final number could be smaller.
The study will measure how many days patients didn’t need mechanical ventilation over a 28-day period. French pharmaceutical company LFB SA is providing the immunoglobulin but otherwise won’t be involved, Tarek Sharshar, one of the investigators, said.
Studying IVIG “will tell you what it can do in the absence of having Covid-specific antibodies,” Octapharma’s Dr. Kreuwel said.