Regeneron Pharmaceuticals said its two-antibody “cocktail” REGN-COV2 met its primary endpoint of significantly reducing viral load and medical visits in ambulatory adults with COVID-19 in a Phase II/III trial—but the company is reviewing a possible change to dosages in the study after finding no significant difference in efficacy between the high and low doses of the treatment.

Regeneron yesterday released data from a second group of 524 patients in the Phase II/III portion (NCT04425629) of an adaptive Phase I/II/III trial evaluating the safety, tolerability, and efficacy of Regeneron’s antibody cocktail in ambulatory adult patients with COVID-19.

The latest results confirm earlier positive data on viral load and medical visits announced by the company in September from the first 275 patients dosed in the randomized, double-blind trial, which has an estimated enrollment of 2,104 participants.

The new data showed that the average daily reduction in viral load through day 7 in patients with “high” viral load (defined as greater than107 copies/mL) was 0.68 log10 copies/mL greater with REGN-COV2 compared to placebo. That reduction increased to 1.08 log greater with REGN-COV2 treatment by day 5—an outcome that Regeneron said corresponded to REGN-COV2 patients having on average a greater than 10-fold reduction in viral load vs. placebo.

In the overall patient group that began the study with detectable virus, the average daily reduction in viral load through day 7 was 0.36 log10 copies/mL greater with REGN-COV2 compared to placebo.

“We continue to see the strongest effects in patients who are most at risk for poor outcomes due to high viral load, ineffective antibody immune response at baseline, or pre-existing risk factors,” George D. Yancopoulos, MD, PhD, Regeneron’s president and chief scientific officer, said in a statement.

Investors reacted to Regeneron’s latest data by sending the company’s shares up 2.3%, to $580 a share from $567.04 a share in after-hours trading last night as of 6:52 pm.

57% Fewer medical visits 

REGN-COV2 also met the trial’s key clinical endpoint by leading to a 57% reduction through day 29 of reducing related medical visits—defined as hospitalizations, emergency room, urgent care visits and/or physician office/telemedicine visits.

The antibody cocktail also reduced COVID-19 related medical visits by 72% in patients with one or more risk factors that included being over 50 years of age; a body mass index greater than 30; cardiovascular, metabolic, lung, liver or kidney disease; or immunocompromised status.

Regeneron in its release focuses first on the reduction of viral load (for obvious reasons), but the real beauty that every person out there can understand is the 57% reduction in follow-on medical visits. That’s real world benefit, and I hope this message is amplified,” tweeted Brad Loncar, CEO of Loncar Investments, which tracks developments in cancer immunotherapy and the broader biopharma industry.

Yancopoulos said Regeneron has shared its latest results with the FDA, which is reviewing the company’s request to authorize the low dose of REGN-COV2 in adults with mild-to-moderate COVID-19 who are at high risk for poor outcomes.

The trial’s Phase III portion is ongoing.

Reviewing potential dosing changes 

Regeneron also disclosed that is reviewing potential changes to dosing in the ongoing outpatient trial “given the current limited supply of REGN-COV2,” and in response to a study finding that showed no significant difference in virologic or clinical efficacy between REGN-COV2’s low dose of 2.4 g, and its high dose of 8 g.

That finding differs with initial data from the trial’s first 275 patients released by Regeneron on September 29, which showed that the 8 g dose showed better results than the 2.4 g low dose and placebo. Patients taking the 8 g dose showed a viral load reduction compared to placebo of 0.51 log10 copies/mL, vs. 0.23 log10 copies/mL for 2.4 g dose patients.

That variance of results may reflect differences in demographics between the 275-patient population and the entire population studied to date of 799 patients.

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%,” Regeneron said). On average, patients were 44 years of age. In total, 49% of participants were male and 51% were female.

Approximately 45% of patients were seropositive, 41% were seronegative, and 14% were categorized as “other” due to unclear or unknown serology status.

Among the overall 799-patient population, approximately 38% of patients were seropositive, 51% were seronegative, and 11% were “other.”

Approximately 50% of patients were Hispanic, 9% were African American, and 60.5% had one or more underlying risk factors for severe COVID-19, including obesity (37%). The average age of patients was 42.2 years old. In total, 47% of participants were male and 53% were female.

Trump treatment 

The high dose of REGN-COV2 was among the treatments taken by President Donald Trump during his hospitalization for COVID-19 earlier this month.

REGN-COV2 is a combination of two monoclonal antibodies, REGN10933 and REGN10987, that are designed to both treat people with COVID-19 and to prevent SARS-CoV-2 infection. Both were produced through Regeneron’s monoclonal antibody discovery platform VelocImmune®, part of the company’s VelociSuite™ technologies.  Both antibodies are designed to bind non-competitively to different sides of the receptor-binding domain (RBD) of SARS-CoV-2’s spike protein.

REGN-COV2 is one of 19 “front runners” among more than 300 COVID-19 drug and vaccine candidates on GEN’s COVID-19 Drug & Vaccine Tracker.

REGN-COV2 advanced to Phase III trials in July. The trial in ambulatory adults is one of four late-stage clinical trials in which REGN-COV2 is under study, with an estimated combined recruitment of at least 11,074 participants. The other three trials are:

  • The Phase II/III portion (NCT04426695) of an adaptive Phase I/II/III trial assessing the safety, tolerability, and efficacy of Regeneron’s antibody cocktail in hospitalized adult patients with COVID-19, with an estimated enrollment of 2,970 participants.
  • A portion of the 15,000-patient open-label, Phase III RECOVERY (Randomized Evaluation of COVid-19 thERapY) trial (NCT04381936) that is examining the effectiveness of the cocktail plus standard of care in at least 2,000 hospitalized COVID-19 patients to be chosen at random in the U.K., and comparing that to another 2,000 patients who already receive standard of care alone.
  • A Phase III trial (NCT04452318) designed to assess REGN-COV2’s ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient, such as a patient’s housemate. The trial has an estimated enrollment of 2,000 participants.
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