Regeneron recently announced that the US Food and Drug Administration (FDA) has accepted REGN-EB3 for a new biologics license application (BLA) and will conduct a priority review. REGN-EB3 is an investigational triple antibody cocktail therapy for the treatment of Ebola virus infection. The FDA has designated a target action date of October 25, 2020.
REGN-EB3 is a mixture of 3 fully human IgG1 monoclonal antibodies, developed by regenerative using proprietary VelociSuite® rapid response technology, which is currently being applied to the development of a new type of new coronavirus pneumonia (COVID-19) Antibody therapy. Ebola virus is the culprit of Ebola hemorrhagic fever (EHF), an acute viral infectious disease. Symptoms include fever, headache, joint and muscle pain, fatigue, diarrhea, vomiting, stomach pain, loss of appetite and Abnormal bleeding. In the United States and the European Union, REGN-EB3 has been granted orphan drug qualifications and has been granted Breakthrough Drug Qualifications (BTD) in the United States. In addition to REGN-EB3, a monoclonal antibody mAb114 from Ridgeback Biotherapeutics to treat Ebola virus infection has also been granted orphan drug qualification, BTD, and priority drug qualification (PRIME) in the United States and the European Union.
REGN-EB3 BLA is based on data from a randomized controlled PALM clinical trial in the Democratic Republic of Congo. The trial tested 4 therapies, including 3 antibody therapies (antibody cocktail therapy ZMapp, triple antibody cocktail therapy REGN-EB3, therapeutic monoclonal antibody mAb114) and an antiviral drug remdesvir (redcivir), of which ZMapp Used as a control. In August 2019, the trial was terminated early, and preliminary results showed that compared with the control group ZMapp, REGN-EB3 and mAb exceeded the pre-defined death prevention advantage threshold and showed higher efficacy in many ways, including reduction Mortality and the time when the Ebola virus is no longer detected in the blood is shorter.
Preliminary evaluation results from 499 subjects confirmed that subjects receiving REGN-EB3 and mAb114 had a greater chance of survival than the other two groups of subjects. The specific data are: (1) mortalities of remdesvir, ZMapp, mAb114, and REGN-EB3 are 53%, 49%, 34%, and 29%, respectively; (2) Early treatment after infection and low blood virus Among the patients, the data is stronger, and the mortality rates are: 33%, 24%, 11%, and 6%, respectively. Currently, the mortality rate for the entire Ebola outbreak is 67%. Based on the above data, the PALM study was terminated early, and REGN-EB3 and mAb114 were selected as drugs for the randomized treatment of all future patients in the extension phase to further evaluate the safety of evaluation until the final clinical trial results are obtained.
Dr. George D. Yancopoulos, co-founder, president and chief scientific officer of Regener said: "REGN-EB3, developed using Regener ’s proprietary VelociSuite® rapid response technology, has been shown to save lives in the PALM trial. The standard of care has evaluated multiple therapies. Regener is now using the same method to develop an antibody drug that may prevent and treat new coronavirus pneumonia (COVID-19), and preliminary clinical trials are expected to begin in June. "
The regenerative VelociSuite technology can effectively create and select fully human antibodies against specific biological targets, which is especially important for solving new and / or rapidly spreading pathogens (such as Ebola and COVID-19). These technologies facilitate the rapid cloning and production of optimized fully human antibodies from VelocImmune® mice (with genetically modified humanized immune systems) and human volunteers in the recovery phase, and allow the rapid upgrade of fully human antibodies to manufacture high Quality cell line production and large-scale bioreactor manufacturing. Once strong therapeutic antibody candidates are identified, the company's in-house pre-clinical, clinical, and commercial-scale production capabilities allow rapid expansion of scale and flexibility to meet current needs.
Ebola is the culprit of EHF. It is an acute viral hemorrhagic infectious disease. Symptoms include: fever, headache, joint and muscle pain, fatigue, diarrhea, vomiting , Stomach pain, loss of appetite and abnormal bleeding. These symptoms can appear within 2-21 days after the virus infection, but most commonly within 8-10 days. Ebola virus is not a water-borne or food-borne disease, nor is it transmitted by air. The disease is transmitted by direct contact with the body fluids of infected persons or by equipment (such as needles) that have been contaminated by the virus.
In November 2019, the Merck vaccine product Ervebo (V920) was first approved in the European Union, in the United States in December 2019, and in the first batch of four African countries in February 2020. It was used for the initiative of people aged 18 and over Immunization to prevent Ebola virus disease (EVD) caused by Ebola Zaire.
Ervebo is the world's first Ebola vaccine to receive regulatory approval, marking a historic milestone. Ervebo (V920) uses a defective vesicular stomatitis virus that can infect domestic animals, replacing a gene of the virus with the Ebola virus gene.
In addition to Ervebo, Johnson & Johnson's Ebola preventive vaccine program, the 2-vaccination program (Ad26.ZEBOV, MVA-BN-Filo), entered an accelerated evaluation in the EU in early November 2019. The vaccine plan is: (1) Ad26.ZEBOV as the first injection vaccine, which was developed based on Jansen ’s AdVac technology; (2) After about 8 weeks, MVA-BN-Filo as the second injection vaccine, The vaccine is based on Bavarian Nordic's MVA-BN technology. Currently, Johnson & Johnson is cooperating with WHO to register the above vaccine plan in African countries.