CME INDIA Presentation by Admin.
Long-Term Single Dose Protection from Covid-19
“Today’s (8/11/21) new data demonstrate how a single dose of REGEN-COV can help protect people from COVID-19 for many months after administration. These results demonstrate that REGEN-COV has the potential to provide long-lasting immunity from SARS-CoV-2 infection, a result particularly important to those who do not respond to COVID-19 vaccines including people who are immunocompromised.” – Myron S. Cohen, MD, Lead researcher in the monoclonal antibody efforts for the NIH-sponsored COVID Prevention Network (CoVPN).
What has been found in Indian Study? (1)
By Dr. Rajeev Jayadeven.
- Non randomised study on monoclonal antibody cocktail VS. regular care on 285 high risk patients in India.
- No one in the study progressed to severe disease, whether they received monoclonal antibody or regular care.
- There were 78 patients in the control group.
- Antibody group showed faster symptom resolution and viral clearance.
- In the absence of severe outcomes in the study, the NNT cannot be estimated (the number of people who need to be treated to create one different outcome. NNT in real life especially in the post vaccination era is likely going to be large).
- This study gives a feel for what it would be like to not receive monoclonal antibodies, although it is non-randomised. No bad outcomes in 78 people who did not receive it.
CME INDIA Learning Points
- REGEN-COV, a neutralizing antibody cocktail of casirivimab plus imdevimab.
- It has been shown to reduce viral load and prevent symptomatic disease in household contacts of infected people.
- At present the effectiveness of this cocktail against the currently surging and highly infectious delta variant SARS-CoV-2 is not well known in India. This study was done at Hyderabad. (Fever clinics if AIG Hospitals)
- The present study assessed the effectiveness of cocktail antibody therapy in high-risk SARS-CoV-2-positive cases. (1)
- It was single-center prospective observational cohort study.
- Material-A total of 285 high-risk, RT-PCR-positive SARS-CoV-2 patients presenting within 7 days from the onset of symptoms between July 15 and 29, 2021.
- Casirivimab and imdevimab was given 600 mg each/100 ml saline, other group received standard-of-care (SOC; n = 78) group, which received remdesivir (200 mg on Day 1 and 100 mg/day from Days 2–5.
- Patients treated with mAb did not receive remdesivir.
- The primary aim: to assess the amount of time taken for resolution of symptoms and change in viral load from baseline through Day 7 (interpreted by Ct values).
- Viral genome sequencing was performed in 115 mAb and 25 SOC patients (COVIDseq; Illumina, USA).
- Neutralizing activity of the cocktail against the delta variant was assessed by a pseudovirus neutralization assay in vitro.
What was found?
- Assessing all the symptoms, the number of symptomatic individuals on Day 7 was significantly lower in the cocktail group than in the SOC group (23/108 [21.30%] vs. 39/78 [50.0%]; p = 0.0001).
- Uniquely the remaining patients in placebo group too recovered completely.
- Fewer patients tested positive by RT-PCR on Day 7 in the cocktail group than in the SOC group. (28/108 [25.0%] vs. 26/50 [52.0%]; p = 0.0001.
- The neutralizing activity of the cocktail against the delta variant was comparable to its activity against the original Wuhan-Hu-1 strain.
|Criteria for Use of Monoclonals (FDA)|
|A revised FDA EUA expanded the criteria that may place an individual at higher risk for severe COVID-19 and thus become eligible for anti-SARS-CoV-2 monoclonal antibodies, stating that health care providers should consider the use of monoclonals in individuals with the following characteristics:|
|BMI >25 kg/m2, or if under 18 years, with BMI ≥85th percentile for their age and sex;|
|History of solid organ or BMT transplant, or cardiovascular disease, cancer, CKD or COPD;|
|Older age (for example, age ≥65 years of age);|
|Chronic kidney disease;|
|Immunosuppressive disease or immunosuppressive treatment;|
|Cardiovascular disease (including congenital heart disease) or hypertension;|
|Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate –to severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension);|
|Sickle cell disease;|
|Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies);|
|Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID 19]).|
What is the message of the study?
- Faster resolution of symptoms by Day 3 in the cocktail group indicates an enhanced benefit against worsening in high-risk patients receiving the cocktail early in the disease course.
- The neutralizing efficacy of the antibody cocktail against pseudoviral variants confirms its ability to block the entry of the delta variant.
- Thus REGEN-COV antibody cocktail-treated high-risk SARS-CoV-2 patients infected with the delta variant showed faster resolution of symptoms along with reduced viral loads.
- REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19).
What other study says? (2)
- In another important study, researchers randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection.
- This was to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection.
- Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001).
- In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%).
- Message: REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).
- Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively).
- No dose-limiting toxic effects of REGEN-COV were noted.
- Thus, subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons.
Most exciting news on 8/11/21
“In this trial, a single dose of REGEN-COV provided long-term protection against COVID-19, including times of particularly high risk from household exposure, and in the longer-term during ongoing broader exposure,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. “These data add to the increasing body of evidence supporting use of REGEN-COV to prevent COVID-19 in uninfected individuals, which may be especially useful for the many immunocompromised people who do not respond adequately to vaccines and remain ‘prisoners of the pandemic.’ With infections still occurring despite widespread vaccination, the immunocompromised face an ongoing risk of encountering the virus during their daily lives. We intend to rapidly share these additional data with regulatory authorities to help those in most need of protection from COVID-19.”(3)
- Kumar V, J, Banu, S, Sasikala, M, Parsa, KVL, Sowpati, DT, Yadav, R, et al. Effectiveness of REGEN-COV antibody cocktail against the B.1.617.2 (delta) variant of SARS-CoV-2: A cohort study. J Intern Med. 2021; 00: 1- 4. https://doi.org/10.1111/joim.13408
- O’Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan K-C, Sarkar N, et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021;385:1184–95. https://doi.org/10.1056/NEJMoa2109682
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