Phase II data on combination therapy with two investigational antibodies for COVID-19, LY-CoV555 and LY-CoV016, showed significant decreases in viral load by day 11 versus placebo, manufacturer Eli Lilly said on Wednesday.
Yet the company said it has applied for emergency use authorization (EUA) for only one of the antibodies, for which the reported efficacy data were equivocal.
Interim analysis of data from the found a dose of 2,800 mg of LY-CoV555 and 2,800 mg of LY-CoV016, in ambulatory or recently diagnosed patients with mild-to-moderate symptoms, reduced viral load by day 11 by 5.6-fold relative to placebo (P=0.011).
The combination therapy also met secondary endpoints of reduced viral load on day 3 (-0.54 log10, P=0.016) and day 7 (-1.18 log10, P<0.001), the topline results indicated. Area under the curve for change in viral load versus time also showed a significant difference relative to placebo over the 11 days (-6.50, P<0.001).
As well, only one of 112 patients receiving the combination was hospitalized or visited an emergency department (ED) in the 4 weeks after dosing, compared with nine of 156 in the placebo group (0.9% vs 5.8%, P=0.049). In a presumed high-risk subgroup (age ≥65 or BMI ≥35), hospitalization/ED visits were recorded for 0% in the combo therapy group vs 13.5% with placebo (P not reported).
However, pooled data for LY-CoV555 monotherapy at different doses did not reach significance (0.03 log10, P=0.87) at day 11, and trended towards significance on day 3 (-0.32 log10, P=0.065) and day 7 (-0.33 log10, P=0.063).
Yet, Lilly submitted an EUA only for the LY-CoV555 monotherapy for use in "higher risk patients." Four patients (4.0%) experienced hospitalization/ED visits among 101 high-risk patients in the monotherapy groups. Lilly said it's waiting until November to request EUA for the combination therapy while it accumulates more safety data and develops manufacturing capacity.
Mean change in symptom score from day-11 was statistically significant, though numerically modest (approximately -4.6 vs -5.3 points), when comparing monotherapy or combination therapy to placebo.
LY-CoV555 was developed in collaboration with AbCellera and the National Institute of Allergy and Infectious Diseases, while LY-CoV016 (etesevimab) was developed in collaboration with the Chinese Academy of Science.
BLAZE-1 enrolled patients positive for SARS-CoV-2 with mild to moderate COVID-19 symptoms in an ambulatory setting. More than 850 participants in BLAZE-1 have been dosed with LY-CoV555, alone or in combination with LY-CoV016. For the latter, 112 patients received the dual therapy and 156 were included in a placebo group. Enrollment is continuing, the company said.
Over half of patients in all groups were women, with a median age of 44 to 46, and about 38% to 44% were Hispanic or Latino. Over three-quarters of all groups reported "mild" COVID-19 with about 5 day symptom duration, and a median symptom score of 6-7.
Examining safety, there were no clinically meaningful differences observed between groups. Rates of treatment-related adverse events were comparable between LY-CoV555 (26% and 23%, respectively), but lower in the combination therapy group (about 13%). Nausea, diarrhea, and vomiting were treatment-related adverse events occurring in at least 1% of all patients.
On a call with investors, Lilly's chief scientific officer, Dan Skovronsky, said Lilly planned to keep exploring a minimally effective dose, noting they were prepared to supply 1 million doses of monotherapy and 50,000 doses of combination therapy in Q4 of 2020. The company is also planning a "pragmatic, open-label study" with monotherapy and the combination focusing on clinical outcomes including death.
A phase III trial, , is now in progress with LY-CoV555 monotherapy in nursing home residents and staff.
Lilly said it will submit interim BLAZE-1 data to a peer-reviewed publication.
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