Clinical and economic benefits of lenzilumab plus standard of care compared with standard of care alone for the treatment of hospitalized patients with COVID-19 in the United States from the hospital perspective

Figures & data

Figure 1. Calculator structure. Abbreviations. N/A, not applicable; SOC, standard of care. *It was assumed that the use of SOC drugs would not be affected by the concomitant use of lenzilumab, resulting in no cost differences for SOC drugs between both groups. This assumption was supported by the balanced use of remdesivir and corticosteroids in both treatment arms of the LIVE-AIR trial¹⁵. **Rehospitalization costs are optional in the calculator. They were not included in the base case analysis but were included for scenario analysis #5.

Table 1. Treatment efficacy inputs from LIVE-AIR trial data^34a.

	Failure to achieve SWOV^b	Mortality^b	Time in ICU (days)^c	Time on IMV (days)^c
Base case: aged <85 years with CRP < 150 mg/L, receiving remdesivir
Lenzilumab plus SOC (n = 123)	9.2%	7.5%	3.79	2.12
	(5.2–15.9)	(4.0–13.9)	(8.2)	(20.7)
SOC alone (n = 131)	24.8%	17.3%	6.76	6.02
	(18.2–33.2)	(11.7–25.1)	(11.2)	(16.9)
Scenario #1: aged <85 years with CRP < 150 mg/L
Lenzilumab plus SOC (n = 159)	8.4%	6.5%	3.48	1.92
	(5.0–14.0)	(3.5–11.7)	(7.8)	(21.1)
SOC alone (n = 178)	21.2%	13.9%	6.21	5.25
	(15.9–28.1)	(9.6–20.9)	(10.6)	(17.5)
Scenario #2: full LIVE-AIR mITT population
Lenzilumab plus SOC (n = 236)	15.6%	9.5%	5.40	3.53
	(11.5–20.9)	(6.4–14.1)	(9.6)	(19.2)
SOC alone (n = 243)	22.1%	13.9%	6.61	5.38
	(17.4–27.9)	(10.1–19.0)	(10.7)	(17.5)
Scenario #3: Black and African American with CRP < 150 mg/L
Lenzilumab plus SOC (n = 25)	4.0%	4.0%	1.48	1.12
	(0.6–25.2)	(0.6–25.6)	(5.7)	(22.4)
SOC alone (n = 26)	29.3%	17.1%	6.54	6.62
	(15.1–51.9)	(6.8–39.4)	(11.1)	(16.6)
Scenario #4: Black and African American
Lenzilumab plus SOC (n = 38)	13.2%	7.9%	4.68	3.11
	(5.7–28.8)	(2.6–22.5)	(9.8)	(19.7)
SOC alone (n = 33)	29.1%	16.5%	7.06	6.48
	(16.3–48.5)	(7.2–35.2)	(10.9)	(16.8)

Abbreviations. CRP, C-reactive protein; ICU, intensive care unit; IMV, invasive mechanical ventilation; mITT, modified intent-to-treat; SOC, standard of care; SWOV, survival without ventilation.

^a All data were censored at 28 days following trial enrollment. Data are presented for the mITT population.

^b These values were derived from Kaplan-Meier analysis. 95% confidence intervals are reported in brackets.

^c Values reported are means with standard deviations.

Table 2. Hospital resource costs and use inputs from LIVE-AIR trial data^a.

	No ICU, no IMV	ICU, but no IMV	IMV, but no ICU^b	Both ICU and IMV
Hospital resource costs^10
Cost per day	$2,348	$2,676	$3,452	$4,207
Patient distributions^34
Base case: aged <85 years with CRP < 150 mg/L, receiving remdesivir
Lenzilumab plus SOC (n = 123)	72.4%	18.7%	0.0%	8.9%
SOC alone (n = 131)	62.6%	13.0%	0.8%	23.7%
Scenario #1: aged <85 years with CRP < 150 mg/L
Lenzilumab plus SOC (n = 159)	72.3%	19.5%	0.0%	8.2%
SOC alone (n = 178)	60.1%	19.1%	0.6%	20.2%
Scenario #2: full LIVE-AIR mITT population
Lenzilumab plus SOC (n = 236)	64.4%	20.3%	0.0%	15.3%
SOC alone (n = 243)	58.0%	20.2%	0.4%	21.4%
Scenario #3: Black and African American with CRP < 150 mg/L
Lenzilumab plus SOC (n = 25)	84.0%	12.0%	0.0%	4.0%
SOC alone (n = 26)	57.7%	11.5%	3.9%	26.9%
Scenario #4: Black and African American
Lenzilumab plus SOC (n = 38)	71.1%	15.8%	0.0%	13.2%
SOC alone (n = 33)	54.6%	15.2%	3.0%	27.3%
Time to recovery (days)^34
Base case: aged <85 years with CRP < 150 mg/L, receiving remdesivir
Lenzilumab plus SOC (n = 123)	7.09	13.68	16.32	25.09
SOC alone (n = 131)	7.04	9.94	17.88	27.48
Scenario #1: aged <85 years with CRP < 150 mg/L
Lenzilumab plus SOC (n = 159)	6.49	12.43	16.61	25.54
SOC alone (n = 178)	7.07	8.82	17.93	27.56
Scenario #2: full LIVE-AIR mITT population
Lenzilumab plus SOC (n = 236)	6.85	12.87	17.29	26.58
SOC alone (n = 243)	7.47	10.00	17.19	26.43
Scenario #3: Black and African American with CRP < 150 mg/L
Lenzilumab plus SOC (n = 25)	6.57	14.00	18.22	28.00
SOC alone (n = 26)	7.47	10.00	17.19	26.43
Scenario #4: Black and African American
Lenzilumab plus SOC (n = 38)	6.85	14.67	18.22	28.00
SOC alone (n = 33)	7.00	13.40	16.91	26.00

Abbreviations. CRP, C-reactive protein; ICU, intensive care unit; IMV, invasive mechanical ventilation; mITT, modified intent-to-treat; SOC, standard of care.

^a All data were censored at 28 days following trial enrollment. Data are presented for the mITT population.

^b In the absence of time to recovery data for the “IMV, but no ICU” group from the LIVE-AIR trial, this was calculated as the time to recovery for the “both ICU and IMV” group multipled by (12.1/18.6), the ratio for mean length of stay between “IMV, but no ICU” and “both ICU and IMV”, respectively from Di Fusco and colleagues¹⁰.

Table 3. Estimated clinical benefits of lenzilumab plus SOC over SOC alone per treated patient.

	Base case: aged < 85 years with CRP < 150 mg/L, receiving remdesivir	Scenario #1: aged < 85 years with CRP < 150 mg/L	Scenario #2: full LIVE-AIR mITT population	Scenario #3: Black and African American with CRP < 150 mg/L	Scenario #4: Black and African American
Failure to achieve SWOV^a
Lenzilumab plus SOC	9.2%	8.4%	15.6%	4.0%	13.2%
SOC alone	24.8%	21.2%	22.1%	29.3%	29.1%
NNT for one patient to achieve SWOV	6	8	15	4	6
Ventilator use
Lenzilumab plus SOC	8.9%	8.2%	15.3%	4.0%	13.2%
SOC alone	24.4%	20.8%	21.8%	30.8%	30.3%
Reduced IMV use	15.5%	12.6%	6.5%	26.8%	17.1%
Mortality^a
Lenzilumab plus SOC	7.5%	6.5%	9.5%	4.0%	7.9%
SOC alone	17.3%	13.9%	13.9%	17.1%	16.5%
NNT for one life saved	10	14	23	8	12
Time to recovery (days)
Lenzilumab plus SOC	9.93	9.21	11.09	8.32	10.87
SOC alone	12.33	11.61	12.08	13.24	13.45
Bed days saved	2.40	2.40	0.99	4.92	2.58
Time in ICU (days)
Lenzilumab plus SOC	3.79	3.48	5.40	1.48	4.68
SOC alone	6.76	6.21	6.61	6.54	7.06
ICU days saved	2.97	2.73	1.21	5.06	2.38
Time on IMV (days)
Lenzilumab plus SOC	2.12	1.92	3.53	1.12	3.11
SOC alone	6.02	5.25	5.38	6.62	6.48
IMV days saved	3.90	3.33	1.85	5.50	3.37

Abbreviations. CRP, C-reactive protein; ICU, intensive care unit; IMV, invasive mechanical ventilation; mITT, modified intent-to-treat; NNT, number needed to treat; SOC, standard of care; SWOV, survival without ventilation.

^a These values were derived from Kaplan-Meier analysis.

Table 4. The estimated economic impact of lenzilumab plus SOC versus SOC alone per treated patient.

	Drug acquisition costs	Drug administration costs	Hospital resource use costs	Rehospitalization costs	Total treatment costs	Cost difference^a
Base case: aged <85 years with CRP < 150 mg/L, receiving remdesivir
Lenzilumab plus SOC	$10,000	$105	$28,328	–	$38,433	−$3,190
SOC alone	$0	$0	$41,622	–	$41,622
Scenario #1: aged <85 years with CRP < 150 mg/L
Lenzilumab plus SOC	$10,000	$105	$26,314	–	$36,419	−$1,858
SOC alone	$0	$0	$38,277	–	$38,277
Scenario #2: full LIVE-AIR mITT population
Lenzilumab plus SOC	$10,000	$105	$34,458	–	$44,563	$4,952
SOC alone	$0	$0	$39,611	–	$39,611
Scenario #3: Black and African American with CRP < 150 mg/L
Lenzilumab plus SOC	$10,000	$105	$22,166	–	$32,270	−$13,154
SOC alone	$0	$0	$45,424	–	$45,424
Scenario #4: Black and African American
Lenzilumab plus SOC	$10,000	$105	$33,128	–	$43,233	−$2,763
SOC alone	$0	$0	$45,996	–	$45,996
Scenario #5: base case including rehospitalization costs
Lenzilumab plus SOC	$10,000	$105	$28,328	$3,188	$41,621	−$5,154
SOC alone	$0	$0	$41,622	$5,152	$46,774

Abbreviations. CRP, C-reactive protein; mITT, modified intent-to-treat; SOC, standard of care.

^aNegative numbers indicate net cost savings with lenzilumab, whereas positive numbers indicate a net increase in per-patient costs with lenzilumab.

Table 5. Sensitivity analyses.

	Base case values	Sensitivity values	Sensitivity analysis results^a	Difference from base case
Hospital resource costs: +25%
No ICU, no IMV	$2,348	$2,935	−$6,513	104.2% increase in cost savings
ICU, but no IMV	$2,676	$3,345
IMV, but no ICU	$3,452	$4,315
Both ICU and IMV	$4,207	$5,259
Hospital resource costs: −25%
No ICU, no IMV	$2,348	$1,761	$134	104.2% decrease in cost savings
ICU, but no IMV	$2,676	$2,007
IMV, but no ICU	$3,452	$2,589
Both ICU and IMV	$4,207	$3,155
Patient distributions: +25% (IMV and ICU)^b
No ICU, no IMV	72.4%	70.6%	−$1,294	59.4% decrease in cost savings
ICU, but no IMV	18.7%	18.2%
IMV, but no ICU	0.0%	0.0%
Both ICU and IMV	8.9%	11.2%
Patient distributions: −25% (IMV and ICU)^b
No ICU, no IMV	72.4%	74.1%	−$5,085	59.4% increase in cost savings
ICU, but no IMV	18.7%	19.2%
IMV, but no ICU	0.0%	0.0%
Both ICU and IMV	8.9%	6.7%
Lenzilumab drug costs: +10%^b	$10,000	$11,000	−$2,190	31.4% decrease in cost savings
Lenzilumab drug costs: −30%^b	$10,000	$7,000	−$6,190	94.1% increase in cost savings
Time to recovery based on Di Fusco et al.^10^c
No ICU, no IMV	7.09/7.04	6.14/6.10	$2,409	175.5% decrease in cost savings
ICU, but no IMV	13.68/9.94	13.21/9.60
IMV, but no ICU	16.32/17.88	11.04/12.10
Both ICU and IMV	25.09/27.48	16.98/18.60

Abbreviations. ICU, intensive care unit; IMV, invasive mechanical ventilation.

^aNegative numbers indicate net cost savings with lenzilumab, whereas positive numbers indicate a net increase in per-patient costs with lenzilumab.

^bInput values changed only for the lenzilumab plus SOC group.

^cValues adjusted based on the mean length of stay for each level of care reported in Di Fusco and colleagues¹⁰. For each level of care, the risk ratio between the time to recovery for lenzilumab plus SOC arm and the SOC alone arm was calculated from the LIVE-AIR trial. The risk ratio was then multiplied by the respective mean length of stay for SOC alone reported by Di Fusco and colleagues¹⁰ to calculate the adjusted input for time to recovery in the lenzilumab plus SOC arm. Values are shown for lenzilumab plus SOC/SOC alone.

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Data availability statement

The data that support the findings of this study are available through the link below: https://doi.org/10.1101/2021.05.01.21256470