dm+d

Unassigned

New Medicines

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

Information

New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

None
None
Approved (Licensed)
Sep 21FDA has revised the emergency use authorization for bamlanivimab and etesevimab to include emergency use as post-exposure prophylaxis for COVID-19 in adults & children (≥12 yrs weighing ≥40kg) at high risk of progression to severe COVID-19, including hospitalisation or death [4].
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 of coronavirus disease 2019 (COVID-19) in long term care facilities (staff and residents)
Intravenous

Trial or other data

Jun 21The PIII BLAZE-2 study (n=966) found a single IV infusion of bamlanivimab reduced the incidence of COVID-19 compared with placebo (8.5% vs 15.2%; absolute risk difference,−6.6; 95% CI −10.7 to −2.6] percentage points (P
Jun 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 [2]
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].

Treatment of coronavirus disease 2019 (COVID-19) - mild to moderate infection - alone or in combination with etesevimab

Information

Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
Jun 21The EMA has identified five "most promising" COVID-19 therapeutics already in an advanced stage of development that it will prioritise, with the aim of providing more regulatory flexibility with rolling reviews, conditional marketing authorisations and flexible labelling and packaging requirements. At least three of these new products will be authorised by Oct 2021. Bamlanivimab in combination with etesevimab is one of the 5 products [10].
Jun 21National distribution of bamlanivimab and etesevimab has been paused in the US, with results from in vitro assays indicating the antibodies are not active against the gamma and beta variants. Until further notice, the FDA recommends healthcare providers use alternative antibody therapies (e.g. sotrovimab or REGEN-COV) [11].
Apr 21FDA has revoked its EUA for bamlanivimab, when administered alone, for the treatment of mild-to-moderate COVID-19 in adults and certain paediatric patients. Based on its ongoing analysis of emerging scientific data, specifically the sustained increase of SARS-CoV-2 viral variants that are resistant to bamlanivimab alone resulting in the increased risk for treatment failure, the FDA has determined that the known and potential benefits of bamlanivimab, when administered alone, no longer outweigh the known and potential risks for its authorised use. Bamlanivimab in combination with etesevimab remains authorised [9]
Apr 21Company requests FDA to revoke the Emergency Use Authorization for COVID due to the concerns with coronavirus variants [8].
Apr 21US government has stopped distributing bamlanivimab as monotherapy out of concern that it may not be effective against new coronavirus variants [7]
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 [6].
Mar 21CHMP issues positive scientific opinion for bamlanivimab alone and in combination with etesevimab for treatment of confirmed COVID-19 in patients aged ≥12 years that do not require supplemental oxygen for COVID-19 and who are at high risk of progressing to severe COVID-19 [5].
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 [4].
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% [3,4].
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 [1].

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].
Treatment of coronavirus disease 2019 (COVID-19) - mild to moderate infection - alone or in combination with etesevimab
Intravenous

Trial or other data

Jul 21BLAZE-1 RCT (n=1035) found bamlanivimab plus etesevimab led to a lower incidence of covid-19–related hospitalization and death than placebo (2.1% vs. 7.0%; p<0.001) and accelerated decline in SARS-CoV-2 viral load among high-risk ambulatory patients [12].
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 [6]
Feb 21The US EUA is based on data from the BLAZE-1 trial which demonstrated bamlanivimab and etesevimab together reduced the risk of COVID-19 hospitalizations and death by 70%. 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 hospitalisation 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 PII and PIII 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 PII 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 PIII trial with bamlanivimab 2800 mg and etesevimab 2800 mg together [4].
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 [2].