Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn) has been approved for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including newborns of mothers who have tested positive for the infection.
The approval means Regeneron will start delivering doses of Inmazeb to the US over the next six years: in a deal worth around $345m.
Regeneron: 'Decades of investment have led to this important moment'
Zaire ebolavirus, known more commonly as the Ebola virus, is one of four Ebolavirus species that can cause a potentially fatal human disease. Ebola virus is transmitted through direct contact with blood, body fluids and tissues of infected people or wild animals; as well as with surfaces and materials (such as bedding and clothing) contaminated with these fluids.
Inmazeb targets the glycoprotein on the surface of Ebola virus. The virus uses the glycoprotein to attach to the cell receptor and fuse viral and host cell membranes, allowing the virus to enter the cell. The three antibodies in Inmazeb can bind to this glycoprotein - simultaneously targeting different, non-overlapping epitopes on the glycoprotien - and thus and block attachment and entry of the virus.
George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron, said: “We are incredibly proud that the FDA has approved Inmazeb. This is the first time the FDA has approved a treatment specifically for Ebola, which has caused a number of deadly outbreaks.
“Decades of investment in our VelociSuite rapid response technologies, the dedication of world-class scientists, and the courageous contributions of healthcare providers and patients, together with remarkable cooperation between leading international health organizations and governments, have led to this important moment.
“As we apply the same sophisticated technologies and manufacturing capabilities against COVID-19, we hope this will be one of many demonstrations of how the power of science can be successfully deployed against dangerous infectious diseases.”
$345m deal with BARDA in the US
Inmazeb – also called REGN-EB3 – was developed in collaboration and with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), as the US builds national preparedness for public health emergencies.
As part of an agreement announced in July, Regeneron will deliver doses of Inmazeb over six years to BARDA, with Regeneron receiving $10m in 2021 and an average of $67m per year for the following five years (2022-2026).
Regeneron says it is also committed to making the medicine available further afield. “With BARDA support, we continue to provide Inmazeb for free in response to outbreaks in the Democratic Republic of the Congo (DRC) through the MEURI protocol for compassionate use. Regeneron is actively working with non-governmental organizations and public health agencies to ensure continued access to Inmazeb in low- and middle-income countries.”
The FDA approved Merck’s Ervebo, the first vaccine for the prevention of Ebola virus disease, in December 2019.
Inmazeb: PALM Trial in the DRC
Inmazeb is administered as a single, weight-based intravenous infusion (50mg atoltivimab, 50mg maftivimab and 50mg odesivimab per kg).
The safety and efficacy of Inmazeb was established through the PALM Trial: which was a randomized, multicenter, controlled trial of 681 patients in 2018 in the DRC. The WHO, the National Institutes of Health (NIH) and the Institut National de Recherche Biomédicale (INRB) in the DRC jointly sponsored and served as co-principal investigators of the trial.
In 2019 the trial was stopped early following a pre-specified interim analysis that showed superiority of Inmazeb to ZMapp and remdesivir with respect to mortality.
Seeking EUA: antibody combination for COVID-19
Regeneron submitted a request last week for Emergency Use Authorization (EUA) for its REGN-COV2 investigational antibody combination for COVID-19: which was given to US President Donald Trump as part of his treatment.
This COVID-19 antibody cocktail uses the same 'rapid response' technologies as its Ebola treatment: through its VelociSuite set.
Specifically, the company used VelociGene to enable rapid, automated and high-scale manipulation of mouse DNA; VelocImmune to produce fully human monoclonal antibodies and VelociMab for high-throughput screening of its therapeutic antibody candidates to identify the best options for its cocktail, among other technologies.
Another common factor between the two antibody cocktails is Regeneron's multi-antibody approach that it applies to infectious diseases. After generating all the potential antibody candidates, it then selects complementary antibodies that target the virus in different ways.