Alyssa Chang, Contributing Photographer

On March 22, the U.S. Food and Drug Administration, or FDA, issued an emergency use authorization for Pemgarda — a new drug that prevents COVID-19 infection — for certain adults and adolescents, potentially offering a new line of defense for millions of immunocompromised individuals. 

The FDA’s decision now allows authorized healthcare professionals to administer the drug to immunocompromised persons over 12 years old who are unlikely to mount an effective immune response to COVID-19 vaccination. According to Shiv Gandhi, an infectious diseases clinical fellow at the School of Medicine, Pemgarda may help immunocompromised patients avoid suffering from any severe symptoms or infection.

“There is a subset of patients that, despite a number of vaccines, still failed to mount a meaningful immune response,” Gandhi told the News. “For those patients, products like this could be useful.” 

Pemgarda is a monoclonal antibody infusion, meaning that doctors administer lab-made clones of an antibody found in the immune system to the body via an IV tube. These proteins then act like the cloned antibody, defending the body against foreign invaders. The infusion, Gandhi said, maintains a protective antibody level for about three months, providing immunocompromised patients with the antibody for COVID-19 they can’t produce on their own. 

However, after those three months, antibody levels wane, and patients are again at risk for infection. Due to this dip in antibodies, the FDA declared that patients may receive Pemgarda infusions every three months.

How does Pemgarda work?

After Pemgarda is administered into the body, antibodies latch onto the SARS-CoV-2 — the name of the virus that causes COVID-19 — receptor binding domain on the virus’ exterior. Normally, the virus receptor tries to bind to a receptor on the outside of a human cell to grant the virus entry. To prevent this, the infused antibody binds to the spike protein of the virus that binds to the human cell receptor, acting as a buffer to prevent the virus binding domain from properly connecting and entering the cell. 

According to Akiko Iwasaki, an immunobiology professor at the School of Medicine, these monoclonal antibody measures have been effective against COVID-19, but they still have limitations.

“Previous monoclonal antibodies were excellent in preventing and treating COVID-19 at the time they were developed,” Iwasaki wrote in an email to the News. “However, variants of concern keep emerging with spike proteins that have undergone significant mutations, enabling them to evade detection by such antibodies.”

SARS-CoV-2 is constantly evolving, and it continues to mutate and change the morphology of its spike protein. While antibodies can recognize these spike proteins and neutralize the virus, if the spike proteins change following a mutation, the virus can evade detection and enter cells.

For Gandhi, these high mutation rates have rendered previous monoclonal antibody treatments ineffective. 

“There was a product that was designed similarly to this that was used for pre-exposure prophylaxis in immunocompromised patients called ‘Evusheld,’ and these preventative measures were all pulled from the market because SARS-CoV-2 evolved and developed mutations in the spike protein that preempted their activity,” Gandhi said.

Though this limitation is inherent to all monoclonal antibody treatments, Gandhi said Pemgarda is still effective against all previous SARS-CoV-2 variants.

Still, Pemgarda produces certain side effects, including redness and swelling at the infusion site, feelings of illness after the infusion and a risk of a severe — even life-threatening — allergic reaction.

“I think for those reasons, the patient population that this will be useful for is quite limited to the most severe immunocompromised patients where the benefits would outweigh the risks,” Gandhi said.

Gandhi noted that patients born with hereditary mutations in their immune system and those who develop conditions — such as blood cancers — or are receiving treatment that suppresses their immune system could all benefit from Pemgarda. 

According to Albert Ko, professor of public health at the School of Public Health, the development of monoclonal antibodies infusions for COVID-19 like Pemgarda will help inform how future viruses are handled, despite the limitations of the infusions.

“What we’ve learned over the pandemic, [such as] how we could make monoclonal antibodies to a pandemic threat really gave us new insights,” Ko told the News. “The knowledge we’ve made from COVID is really going to be able to help us think about how we can use that advice not only to treat patients but also with prophylaxis to protect vulnerable populations, such as the immunocompromised.”

Pemgarda was developed by Invivyd, a biopharmaceutical company founded in 2020. 

Carlos Salcerio covers the Yale School of Medicine and the Yale School of Nursing for the SciTech desk. Originally from Cuba, he is a prospective pre-medical student majoring in Molecular Biophysics and Biochemistry in Jonathan Edwards College.