INO-4500 DNA Vaccine Description 2022
INO-4500 is a DNA vaccine candidate. On November 17, 2022, the company discontinued the development of product candidates targeting Lassa Fever (INO-4500) following initial analyses of data from studies conducted by INOVIO and funded by CEPI.
In addition, INOVIO is leveraging its optimized plasmid design and delivery technology to develop DNA medicines to treat and prevent infectious diseases. INO-4500 is the first vaccine candidate for Lassa fever to enter human trials, says the company.
INOVIO's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using one of INOVIO's proprietary hand-held CELLECTRA smart devices. INOVIO's DNA medicines are made using a process called SynCon®. SynCon uses a proprietary computer algorithm designed to identify and optimize the DNA sequence of the target antigen, whether it is a virus or a tumor. Once this sequence has been determined, the DNA is synthesized or reorganized, and manufacturing can begin, says the company.
DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA synthesized or reorganized by computer sequencing technology and designed to produce a specific immune response in the body.
On February 23, 2021, INOVIO announced the first participant was dosed in a Phase 1B clinical trial for INO-4500 in Ghana, Africa. The Phase 1B clinical trial (LSV-002) is ongoing at the Noguchi Memorial Institute for Medical Research in Accra, Ghana. It is the first vaccine clinical trial for Lassa fever to be conducted in West Africa.
Plymouth Meeting, Pennsylvania-based INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and diseases INOVIO has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses associated with MERS and COVID-19 diseases being developed under grants from the Coalition for Epidemic Preparedness Innovations and the U.S. Department of Defense.
INO-4500 Indication
The U.S. CDC says Lassa fever is an animal-borne, or zoonotic, acute viral illness. It is endemic in West Africa, including Sierra Leone, Liberia, Guinea, and Nigeria. Neighboring countries are also at risk, as the animal vector for the Lassa virus, the "multimammate rat" (Mastomys natalensis), is distributed throughout the region.
The illness was discovered in 1969 and is named after the town in Nigeria where the first cases occurred. An estimated 100,000 to 300,000 infections of Lassa fever occur annually, with approximately 5,000 deaths, says the CDC. Unfortunately, surveillance for Lassa fever is not standardized; therefore, these estimates are crude. However, in some areas of Sierra Leone and Liberia, it is known that 10-16% of people admitted to hospitals annually have Lassa fever, demonstrating the serious impact the disease has on the region.
INO-4500 Dosage
The INO-4500 vaccine is conducting clinical tests for the prevention of Lassa Fever. Inovio's proprietary Cellectra electroporation device injects this vaccine into the muscle or skin. Injection of the DNA plasmid into a patient generates robust in vivo monoclonal antibody production. Thus, this approach can potentially generate in vivo production of therapeutic antibodies.
INOVIO's Phase 1B clinical trial, LSV-002, dosing regimen involves two vaccinations at 0 and 28 days with either 1.0 mg or 2.0 mg dosing levels. This trial will inform dose selection for subsequent Phase 2 studies in West Africa.
INO-4500 News 2018 - 2022
March 22, 2022 - The UK NHS confirmed a systematic review examining preclinical and human pharmacokinetic data and found that the clinical evidence for ribavirin as a treatment for Lassa fever was limited.
March 15, 2022 - The U.S. CC confirmed an outbreak of Lassa fever in Nigeria in Ondo, Edo, Bauchi, Ebonyi, Kogi, Taraba, Enugu, Benue, Gombe, Nasarawa, and the Delta States.
February 21, 2022 - The WHO stated 'Considering the seasonal increases of cases between December and March, countries in West Africa that have endemic Lassa fever are encouraged to strengthen their related surveillance systems to enhance early detection and treatment of cases and to reduce the case fatality rate, as well as to strengthen cross border collaboration.'
February 9, 2022 - The UK Health Security Agency press office confirmed two people had been diagnosed with Lassa fever in the East of England. Before these cases, 8 cases of Lassa fever were imported to the UK since 1980. The last 2 cases occurred in 2009. There was no evidence of onward transmission from any of these cases.
November 7, 2021 - The WHO Africa reported through October 2021 that Nigeria had confirmed 403 cases. A total of 79 individuals have died among those who had confirmed results, yielding a 19.6% CFR this year. The CFR during the same period in 2020 was 20.7%
October 26, 2021 - INOVIO announced its Phase 1B clinical trial for INO-4500, its DNA vaccine candidate for Lassa fever, and completed full enrollment of 220 participants. This trial is ongoing at the Noguchi Memorial Institute for Medical Research in Accra, Ghana. It is the first vaccine clinical trial for Lassa fever conducted in West Africa, where the viral illness is endemic.
February 23, 2021 - INOVIO announced the first participant was dosed in a Phase 1B clinical trial for INO-4500, its DNA vaccine candidate for Lassa fever, in Ghana. The Phase 1B clinical trial (LSV-002), ongoing at the Noguchi Memorial Institute for Medical Research in Accra, Ghana, is the first vaccine clinical trial for Lassa fever to be conducted in West Africa, where the infection is endemic.
October 11, 2018 - According to new research published in Nature Communications, a novel vaccine designed to protect people from Lassa fever and rabies showed promise in preclinical testing. The investigational vaccine, called LASSARAB, was developed and tested by scientists at Thomas Jefferson University in Philadelphia; the University of Minho in Braga, Portugal; the University of California, San Diego; and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
April 11, 2018 - Inovio Pharmaceuticals, Inc. (NASDAQ: INO) and the Coalition for Epidemic Preparedness Innovations announced a partnership under which Inovio will develop vaccine candidates against Lassa fever and Middle East Respiratory Syndrome.
INO-4500 Clinical Trials
Clinical Trial NCT04093076: INOVIO's Phase 1B clinical trial, LSV-002, will enroll approximately 220 adult participants 18-50 years old, with the primary endpoint of evaluating safety and immunogenicity in an African population. The dosing regimen involves two vaccinations at 0 and 28 days with either 1.0 or 2.0 mg dosing levels. In addition to providing valuable insights on the INO-4500 safety and immunogenicity profile, this trial will inform dose selection for subsequent Phase 2 studies in West Africa. Last Update Posted: February 25, 2021. Estimated study completion date: September 2022.
Clinical Trial NCT03805984: Safety, Tolerability, and Immunogenicity of INO-4500 in Healthy Volunteers. This Phase 1 trial is a randomized, double-blinded, placebo-controlled, placebo-controlled trial to evaluate the safety, tolerability, and immunological profile of INO-4500 administered by intradermal (ID) injection followed by electroporation using the CELLECTRA® 2000 device in healthy adult volunteers. Last Update Posted: November 23, 2020. Actual completion date: October 21, 2020.
