Exciting News – FDA Grants Emergency Use Authorization for First COVID Monoclonal Antibody for Pre-Exposure Prevention of COVID for CLL/SLL Patients and Others at Risk!

Tixagevimab and cilgavimab are neutralizing IgG1 monoclonal antibodies (mAbs) that bind to distinct, non-overlapping epitomes (the specific site where an antibody binds) within the receptor-binding domain (RBD) of the spike “s” protein of the SARs-CoV-2 virus. EVUSHELD™ remains an investigational drug as it has not received full FDA approval.

EVUSHELD™ is the first product to receive a EUA for pre-exposure prophylaxis (prevention) of COVID-19 who have moderate to severe compromised immune systems due to a medical condition or the receipt of an immune-suppressive drug. EVUSHELD™ has currently not authorized for post-exposure prevention or treatment of COVID-19 at this time.

Before the approval of the Astra Zeneca product, the FDA had granted EUA status to three monoclonal antibodies for the treatment or prevention (in high-risk patients) of COVID-19.

Bamlanivimab plus etesevimab are neutralizing antibodies that bind to different but overlapping epitopes on the spike protein RBD of SARS-CoV-2. Eli Lilly and Company, an American pharmaceutical company, headquartered in Indianapolis, developed Bamlanivimab plus etesevimab. The US paused the distribution of this product because it had decreased efficacy against the Beta and Gamma variants. However, distribution has resumed to areas with a low incidence of these two variants.

The FDA based its EUA on the review of data from the PROVENT clinical trial (NCT04625725), a phase III, randomized, double-blind (neither the patient nor provider know if the patient receives EVUSHELD™ or placebo). The FDA EUA Approval Letter States, “ it is reasonable to believe that EVUSHELD™ may be effective for use for pre-exposure prophylaxis of COVID-19 in certain adults and pediatric individuals (12 years of age or older and weighing at least 40 kg) as described in the scope of authorization (see below) and when under the conditions described in this authorization the known and potential benefits of EVUSHELD™ outweigh the known or potential risks of such product.”

Distribution of the authorized EVUSHELD™ will be controlled by the United States (US) Government for use consistent with the terms and conditions of this EUA. Astra-Zeneca will supply EVUSHELD™ to authorized distributors who will distribute to healthcare facilities or healthcare providers as directed by the US Government, in collaboration with state and local government authorities as needed;

EVUSHELD™ may only be used in patients who meet the specified age and weight requirements, who are not currently infected with SARS-CoV-2, and who have not had a known recent exposure to an infected person and;

Who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and may not mount an adequate response to COVID-19 vaccination, or

For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine(s) and/or COVID-19 vaccine components.

When I spoke to an Astra-Zeneca Medical Affairs representative during the American Society of Hematology Annual Meeting (ASH2021) this week, they indicated that EVUSHIELD would likely go to larger institutions such as major cancer and organ transplant centers first. This distribution arrangement may be another reason you should have a CLL Specialist on your team.

Based on the current data from the PROVENT study, the duration of response (DoR) is six months. As the study follow-up matures, this DoR may increase, and patients may be re-dosed at six months until an updated DoR time is released.

Unlike the Lilly and Regeneron, COVID-19 mAbs is given intramuscularly (IM) as two injections of 1.5ml each. Because this is a relatively large volume for an IM injection, EVUSHELD™ is injected into the gluteal muscle (buttocks).

EVUSHELD™ is not authorized for post-exposure prevention or treatment because it did not meet the primary endpoint in the STORMCHASER clinical trial. Stormchaser allowed an interval of up to 8 days after exposure, and this appears to be too late for effectiveness. Researchers plan to modify the study design to reduce the maximum number of days after exposure as original data showed promising results in patients who received EVUSHELD™ closer to exposure.

The most common adverse events (AEs) seen in patients who received EVUSHELD™ were headache, cough, pain at the injection site, and fatigue.

This EUA is very important to the CLL/SLL community as it will allow us to receive EVUSHELD™ before being exposed to SARS-CoV-2, the virus that causes COVID-19. CLL/SLL patients with immune compromise due to their disease or treatment have had a much higher incidence of hospitalization and death than the general population, especially before advances in COVID-19 therapies and the availability of vaccines.

Several studies have shown that large numbers of CLL/SLL patients have not made antibodies after two or even three doses of the mRNA vaccines made by Pfizer and Moderna. Many CLL/SLL patients who received the Janssen/Johnson&Johnson vaccine also did not make antibodies after a single dose. The authorization to allow a booster with J&J is too recent for data to be available.
The Leukemia and Lymphoma Society (LLS) study of the effectiveness (seropositive rate) of COVID-19 vaccines among blood cancer patients showed that overall, only 64% of CLL/SLL patients mounted an antibody response after the full initial vaccination schedule. However, the seronegative rates were even higher in CLL patients treated within the last two years with drugs that impair B-cells, including:

- BTK inhibitors such as ibrutinib or acalabrutinib,
- anti-CD20 antibodies such as rituximab, obinutuzumab or ublituximab, or CD-20 containing combinations
- or venetoclax, a BCL2 inhibitor.

You may want to contact your CLL team to get your name added to their list so you can receive this potentially life-saving product when it becomes available.

Since I received the REGEN-COV mAb, I know I feel much less at risk as I had not produced antibodies after four Pfizer and one J&J vaccine. This protection may ease your mind in addition to affording another potential layer of protection.