The first data from a descriptive analysis of a seamless phase 1/2/3 trial of the investigational antibody cocktail REGN-COV2 has reduced viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19.
REGN-COV2 has also shown positive trends in reducing medical visits.
The ongoing, randomized, double-blind trial measures the effect of adding REGN-COV2 to usual standard-of-care, compared to adding placebo to standard-of-care. This trial is part of a larger program that also includes studies of REGN-COV2 for the treatment of hospitalized patients, and for prevention of infection in people who have been exposed to COVID-19 patients.
The descriptive analysis included the first 275 patients enrolled in the trial and was designed to evaluate antiviral activity with REGN-COV2 and identify patients most likely to benefit from treatment; the next cohort, which could be used to rapidly and prospectively confirm these results, has already been enrolled.
Patients in the trial were randomized 1:1:1 to receive a one-time infusion of 8 grams of REGN-COV2 ( high dose ), 2.4 grams of REGN-COV2 ( low dose ) or placebo.
All patients entering the trial had laboratory-confirmed COVID-19 that was being treated in the outpatient setting.
Patients were prospectively characterized prior to treatment by serology tests to see if they had already generated antiviral antibodies on their own and were classified as seronegative ( no measurable antiviral antibodies ) or seropositive ( measurable antiviral antibodies ). Approximately 45% of patients were seropositive, 41% were seronegative and 14% were categorized as other due to unclear or unknown serology status.
As hypothesized, patients in the study consisted of two different populations: those who had already mounted an effective immune response, and those whose immune response was not yet adequate. These populations could be identified serologically by the presence ( seropositive ) or absence ( seronegative ) of SARS-CoV-2 antibodies, and/or by high viral loads at baseline.
Serological status was highly correlated with baseline viral load ( p less than 0.0001 ). Seropositive patients had much lower levels of virus at baseline, and rapidly achieved viral loads approaching lowest levels quantifiable ( LLQ ), even without treatment.
In contrast, seronegative patients had substantially higher viral levels at baseline, and cleared virus more slowly in the absence of treatment.
Serological status at baseline also predicted how rapidly patients had alleviation of their COVID-19 clinical symptoms.
In the untreated ( placebo ) patients, seropositive patients had a median time to alleviation of symptoms of 7 days, compared to seronegative patients who had a median time to alleviation of symptoms of 13 days.
REGN-COV2 rapidly reduced viral load through day 7 in seronegative patients ( key virologic endpoint ). The mean time-weighted-average change from baseline nasopharyngeal viral load through day 7 in the seronegative group was a 0.60 log10 copies/mL greater reduction ( p=0.03 ) in patients treated with high dose, and a 0.51 log10 copies/mL greater reduction ( p=0.06 ) in patients treated with low dose, compared to placebo.
In the overall population, there was a 0.51 log10 copies/mL greater reduction ( p=0.0049 ) in patients treated with high dose, and a 0.23 log10 copies/mL greater reduction ( p= 0.20 ) in patients treated with low dose, compared to placebo.
Patients with increasingly higher baseline viral levels had correspondingly greater reductions in viral load at day 7 with REGN-COV2 treatment. The mean log10 copies/mL reduction in viral load compared to placebo were as follows: viral load higher than 105 copies/mL: approximately 50-60% reduction compared to placebo; viral load higher than 106 copies/mL: approximately 95% reduction compared to placebo; viral load higher than 107 copies/mL: approximately 99% reduction compared to placebo.
Patients who were seronegative and/or had higher baseline viral levels also had greater benefits in terms of symptom alleviation. Among seronegative patients, median time to symptom alleviation ( defined as symptoms becoming mild or absent ) was 13 days in placebo, 8 days in high dose ( p=0.22 ), and 6 days in low dose ( p=0.09 ).
Patients with increasing viral loads at baseline had correspondingly increasing benefit in time to symptom alleviation.
Both doses were well-tolerated. Infusion reactions were seen in 4 patients ( 2 on placebo and 2 on REGN-COV2 ). Serious adverse events occurred in 2 placebo patients, 1 low dose patient and no high dose patients. There were no deaths in the trial.
Among the first 275 patients, approximately 56% were Hispanic, 13% were African American and 64% had one or more underlying risk factors for severe COVID-19, including obesity ( more than 40% ). On average, patients were 44 years of age. In total, 49% of participants were male and 51% were female. ( Xagena )
Source: Regeneron Pharmaceuticals, 2020