Patients on Enjaymo show immune response to COVID-19 vaccines

The vaccines were well tolerated, with no safety concerns identified: Study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with cold agglutinin disease (CAD) who were on Enjaymo (sutimlimab-jome) during clinical trials produced antibodies in response to COVID-19 vaccination, suggesting their ability to mount an immune response was not impaired, a recent study reports.

In patients with a waning immune response, a booster dose was enough to restore protection back to levels even higher than those achieved just after the primary two-dose vaccination schedule, researchers found.

The study, “COVID-19 vaccine safety and immunogenicity in patients with cold agglutinin disease receiving concomitant sutimlimab,” was published as correspondence in the American Journal of Hematology.

CAD occurs when the immune system mistakenly identifies red blood cells as foreign and attacks them with the help of immune proteins, causing their destruction.

Treating CAD often involves the use of medications that weaken the immune system to keep it from attacking red blood cells. This may make patients “more vulnerable to infectious agents such as viruses and bacteria,” the researchers wrote.

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Enjaymo blocks C1s immune protein involved in attack against red blood cells

Given as an infusion directly into the bloodstream, Enjaymo is an antibody that blocks C1s, an immune protein involved in the attack against red blood cells. Thus, blocking C1s is expected to prevent excess red blood cell destruction and ease CAD symptoms.

Enjaymo was approved in the U.S. in 2022 to reduce the need for blood transfusions due to red blood cell destruction in adults with CAD, becoming the first therapy to earn approval for the condition in the country.

It was tested in two Phase 3 clinical trials, CARDINAL (NCT03347396) and CADENZA (NCT03347422), which ran before and during the COVID-19 pandemic. Both were sponsored by Bioverativ, now part of Sanofi, which continues to develop and market Enjaymo.

Patients were encouraged to get vaccinated against COVID-19 while continuing their treatment with Enjaymo. While “interactions with vaccinations are unlikely and antibody production in response to vaccination is not likely to be directly impacted,” if and how Enjaymo interfered with immune responses to COVID-19 vaccination was unknown.

To know more, researchers from Sanofi worked in collaboration with investigators in Italy, Germany, and the U.S. to test the safety and immune response to COVID-19 vaccination in an open-label extension to the CARDINAL and CADENZA trials.

Of the 61 patients who completed both trials, 47 received at least one dose of a COVID-19 vaccine, mostly of the mRNA type, while 14 were not vaccinated, and 11 had an additional booster.

The mean age of vaccinated patients was 68.5 years, and most were female (77%). About half (51%) had received rituximab in the previous five years. A mean of 212 weeks (roughly four years) had elapsed between their last dose of rituximab and their vaccination.

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Patients developed immune response to COVID-19 vaccination

All 27 patients with available data on immunoglobulin G (IgG), the most abundant type of antibody in the blood, developed an immune response to COVID-19 vaccination. The immune response was consistent regardless of previous treatment with rituximab, which may lower the levels of IgG.

The levels of antibodies against spike, a protein found on the surface of the COVID-19-causing virus, were significantly lower in patients whose IgG levels were equal to or less than 8 g/L versus those whose IgG levels were greater than 8 g/L before vaccination (2.9 vs. 3.4).

The median time from the second dose of a COVID-19 vaccine and a booster dose was 183 days, or about six months. In six patients who had a waning immune response after the second dose, the booster restored the antibodies to levels higher than those achieved just after the primary vaccination.

Ten side effects were reported in the seven days following any vaccine dose, and none were deemed serious. Despite reports that COVID-19 or COVID-19 vaccination may trigger CAD, there was no evidence of excess breakdown of red blood cells.

“In conclusion, COVID-19 vaccines were well tolerated, and no safety concerns were identified,” the researchers wrote, noting that despite treatment with Enjaymo, “COVID-19 vaccination response was not impaired.”

These findings “may offer insight into the response to other vaccinations; however, further studies and analyses will be required,” the researchers wrote, adding “solid conclusions cannot be made” from a small sample size.