Bamlanivimab

Unassigned

New Medicines

Prevention in long term care facilities (staff and residents) of coronavirus disease 2019 (COVID-19) - monotherapy

Information

New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
Mar 21EMA CHMP starts started a rolling review of data on bamlanivimab for the treatment of COVID-19. The review will also look at bamlanivimab used in combination with etesevimab. The EMA CHMP positive scientific opinion, issued earlier in the month, was undertaken to provide a harmonised scientific opinion at EU level to support national decision making on the possible use of the antibodies prior to marketing authorisation [9].
Nov 20Granted emergency use by FDA for use in patients, 12 years and over, who aren´t hospitalised but are at high risk of developing severe illness, including elderly patients and those with certain underlying conditions. Lilly advises infusion within 10 days of symptom onset [6].
Aug 20PIII trials in US long term care facilities starts [1].

Category

IgG1 monoclonal antibody directed at spike protein of COVID virus
COVID-19 is an infectious disease caused by coronavirus SARS-CoV-2. Most people infected experience mild to moderate respiratory illness and recover without requiring special treatment. Older people, and those with underlying medical problems are more likely to develop serious illness [2]. Those in long term care are particularly at risk [1].
Prevention in long term care facilities (staff and residents) of coronavirus disease 2019 (COVID-19) - monotherapy
Intravenous

Trial or other data

Jan 21Eli-Lilly report PIII BLAZE-1 trial meets primary endpoint of reduced hospitalisations and deaths from COVID-19; 2.1% of patients given treatment required hospitalisation vs 7% for control. It also reduced viral load and sped up symptom resolution, although data has not been released [8].
Jan 21In PIII BLAZE-2 trial bamlanivimab significantly reduced the risk of contracting symptomatic COVID-19 among residents and staff of long-term care facilities. Symptomatic COVID-19 (the primary endpoint) was reduced in the bamlanivimab treatment arm versus placebo (odds ratio 0.43, p=0.00021). Results for all key secondary endpoints also reached statistical significance [7].
Oct 20Enrollment into the LY-CoV555 sub-study of ACTIV-3 has closed (n=326) and investigators are to be unblinded to the data following a recommendation from the independent Data and Safety Monitoring board. This recommendation was based on a low likelihood that the intervention would be of clinical value in this hospitalised patient population [5].
Oct 20Eli Lilly pause PIII Activ-3 covid-19 antibody (bamlanivimab) trial (n=326) for safety reasons after 5 days of treatment, and a week after application was made for a US emergency use authorisation. Lilly said study had “reached a predefined boundary for safety at day 5”; no further details have been released [4].
Sep 20Interim proof-of-concept data from PII BLAZE-1 trial shows that LY-CoV555 has a direct antiviral effect and may reduce COVID-related hospitalizations. The study enrolled mild-to-moderate COVID-19 pts (outpatients recently diagnosed) who received either placebo, 700 mg, 2800 mg and 7000 mg of the antibody. The primary endpoint of change from baseline in viral load at day 11 was 1.7% for all doses of the antibody vs. 6% in the placebo cohort. That comes to a 72% risk reduction in this particular limited population. No pts progressed to mechanical ventilation or died and pts receiving the antibody had a faster improvement in symptoms vs. placebo. It was well-tolerated with no serious adverse events reported.[3]
Aug 20PIII trial BLAZE-2 starts investigating prevention of SARS-CoV-2 infection and COVID-19 in residents and staff at long-term care facilities in the U.S. who have been exposed to the virus (n=2400). It will test whether a single dose reduces the rate of SARS-CoV-2 infection through 4 weeks, as well as complications of COVID-19 through 8 weeks [1].

Mild to moderate coronavirus disease 2019 (COVID-19) - in combination with etesevimab

Information

Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
Mar 21EMA CHMP starts started a rolling review of data on bamlanivimab and etesevimab for the treatment of COVID-19. The review will also look at bamlanivimab used alone. The previously issued positive scientific opinion was undertaken to provide a harmonised scientific opinion at EU level to support national decision making on the possible use of the antibodies prior to marketing authorisation [4].
Mar 21who are at high risk of progressing to severe COVID-19 [3].
Feb 21Bamlanivimab alone is authorised for emergency use in numerous countries, while bamlanivimab and etesevimab together is currently authorised in the US and Italy. Lilly plans to continue to supply bamlanivimab alone under the authorisations granted in various countries while continuing to accelerate manufacturing of etesevimab for use around the world. Lilly, in collaboration with Amgen, plans to manufacture up to 1 million doses of etesevimab for administration with bamlanivimab by mid-2021. There are 100,000 doses ready immediately and an additional 150,000 doses will be available throughout Q1 21 [2].
Feb 21FDA grants Emergency Use Authorization (EUA) covering patients aged 12 years and over for bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016) 1400 mg, taken together. The FDA made its decision based on phase 3 data from the BLAZE-1 trial showing bamlanivimab and etesevimab together reduced the risk of COVID-19 hospitalisations and death by 70% [1,2].

Category

IgG1 monoclonal antibody directed at spike protein of COVID virus (bamlanivimab) given by infusion over 16 minutes, at the same time as etesevimab (a recombinant fully human monoclonal neutralizing antibody) given over 21 minutes
COVID-19 is an infectious disease caused by coronavirus SARS-CoV-2. Most people infected experience mild to moderate respiratory illness and recover without requiring special treatment. Older people, and those with underlying medical problems are more likely to develop serious illness [2]. Those in long term care are particularly at risk [1].
Mild to moderate coronavirus disease 2019 (COVID-19) - in combination with etesevimab
Intravenous

Trial or other data

Mar 21New data from PIII BLAZE-1 trial (n=769 aged >12 years) showed that bamlanivimab 700mg and etesevimab 1400mg significantly reduced the risk of hospitalisation and death vs. placebo in high-risk pts with newly diagnosed mild-to-moderate COVID-19. Treatment was given in the outpatient setting and early in the course of the disease. By day 29, there were 4 deaths in the bamlanivimab and etesevimab arm vs. 15 with placebo; an 87% reduction in the risk of hospitalisation or death (p<0.0001). Viral load, time to sustained symptom resolution, COVID-19-related hospitalisation, and emergency room (ER) visit or death from any cause – were also improved with the combination. [4]
Feb 21Lilly has completed a PI study of bamlanivimab in hospitalized patients with COVID-19 (NCT04411628). A PII/III study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is ongoing studying bamlanivimab and etesivimab. A PIII study of bamlanivimab for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987) is also ongoing. In addition, bamlanivimab is being tested in the National Institutes of Health-led ACTIV-2 study in ambulatory COVID-19 patients. A PI study (NCT04441931) of etesevimab in healthy US volunteers to evaluate the safety, tolerability, pharmacokinetics and immunogenicity has completed [2].
Feb 21The US EUA is based on Phase 3 data from the BLAZE-1 trial which demonstrated bamlanivimab and etesevimab together reduced the risk of COVID-19 hospitalizations and death by 70 percent. These data replicate earlier results, published in The Journal of the American Medical Association, in a much larger group of patients. Additionally, the outcomes seen with bamlanivimab and etesevimab together are consistent with the reduction in risk of hospitalization or ER visits seen with bamlanivimab alone. The most common adverse event more often reported for patients receiving bamlanivimab and etesevimab together versus placebo was nausea on the day of infusion. While Phase 2 and Phase 3 trials evaluated a range of doses of bamlanivimab alone and bamlanivimab and etesevimab together, data demonstrated consistent and similar clinical effects among all doses studied. Additionally, initial results from an ongoing Phase 2 study provide viral load and pharmacodynamic/pharmacokinetic data which demonstrated bamlanivimab 700 mg and etesevimab 1400 mg together produced similar effects to those observed in the Phase 3 trial with bamlanivimab 2800 mg and etesevimab 2800 mg together [2].