Virus World

– First smallpox antiviral approved for all age groups, including infants, and patients who have difficulty swallowing -

DURHAM, N.C., June 04, 2021 (GLOBE NEWSWIRE) -- Chimerix (NASDAQ:CMRX), a biopharmaceutical company focused on accelerating the development of medicines to treat cancer and other serious diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted TEMBEXA® (brincidofovir) tablets and oral suspension approval for the treatment of smallpox. TEMBEXA is approved for adult and pediatric patients, including neonates. “We are delighted to report our first FDA approved products for the treatment of smallpox, particularly as the importance of pandemic preparedness has been put into focus over the last year. With this approval in hand, we now look forward to advancing our discussions with the Biomedical Advanced Research and Development Authority (BARDA) toward a procurement contract to support national preparedness,” said Mike Sherman, Chief Executive Officer of Chimerix. Chimerix developed the TEMBEXA oral formulations as medical countermeasures for the treatment of smallpox under an ongoing collaboration with BARDA, part of the office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, under contract number HHSO100201100013C. TEMBEXA’s approval is based on efficacy data in two lethal orthopoxvirus animal models of human smallpox disease, the rabbitpox model (New Zealand White rabbits infected with rabbitpox virus) and the mousepox model (BALB/c mice infected with ectromelia virus). In the pivotal studies in each model, TEMBEXA treatment resulted in statistically significant survival benefit versus placebo following delayed treatment after animals were infected with a lethal viral dose. The FDA’s ‘Animal Rule’ allows for testing of investigational drugs in animal models to support effectiveness in diseases which are not ethical or feasible to study in humans. The TEMBEXA U.S. Prescribing Information has a BOXED WARNING for increased risk for mortality when used for longer duration; see below for Important Safety Information.

About Chimerix

Chimerix is a development-stage biopharmaceutical company dedicated to accelerating the advancement of innovative medicines that make a meaningful impact in the lives of patients living with cancer and other serious diseases. Most recently, the Company obtained FDA approval for brincidofovir as a medical countermeasure for the treatment of smallpox. The Company has two other advanced clinical-stage development programs, ONC201 and dociparstat sodium (DSTAT). ONC201 is currently in a registrational clinical program for recurrent H3 K27M-mutant glioma and a blinded independent central review is expected later in 2021. DSTAT is in development as a potential first-line therapy in acute myeloid leukemia.

About Smallpox

Smallpox is a highly contagious disease caused by the variola virus. Historically, smallpox was one of the deadliest diseases in history with a case fatality rate of approximately 30%. Despite successful eradication of smallpox in the 1970s, there is considerable concern that variola virus could reappear, either through accidental release or as a weapon of bioterrorism. According to the U.S. Centers for Disease Control and Prevention (CDC), variola virus is ranked in the highest risk category for bioterrorism agents (Category A) due to its ease of transmission, high mortality rate, and potential to cause public panic and social disruption.

About TEMBEXA

TEMBEXA is an oral antiviral formulated as 100 mg tablets and 10 mg/mL oral suspension dosed once weekly for two weeks. TEMBEXA is indicated for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates. TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease. The effectiveness of TEMBEXA for the treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible and inducing smallpox disease in humans to study the drug’s efficacy is not ethical. TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals. TEMBEXA (brincidofovir) is a nucleotide analog lipid-conjugate designed to mimic a natural monoacyl phospholipid to achieve effective intracellular concentrations of the active antiviral metabolite, cidofovir diphosphate. Cidofovir diphosphate exerts its orthopoxvirus antiviral effects by acting as an alternate substrate inhibitor for viral DNA synthesis mediated by viral DNA polymerase.

FDA Press Release (June 4, 2021):

https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-drug-treat-smallpox 

A gas explosion has sparked a fire at a Russian bioweapons facility which stores viruses including Ebola Smallpox and Anthrax. The blast occurred on Monday after a gas cylinder exploded during scheduled repair work on the fifth floor of the six-story Russian State Centre for Research on Virology and Biotechnology, commonly known as Vector, the facility said in a statement. No biological material was held in the sanitary inspection room where the explosion occurred, and no structural damage was caused to the concrete laboratory building, the center added.

One worker was taken to hospital and is being treated in intensive care for burns, Russia's TASS news agency reported. A fire, covering 30 square meters was later extinguished by fire fighters. The bioweapons facility, located in Koltosvo, in the Novosibirsk region of Siberia, is known for being one of two centers in the world housing samples of smallpox. The US Center for Disease Control and Protection is the only other center in the world known to hold live samples of the disease.

Originally, the center was used to develop biological weapons research during the Cold War Soviet era. Now it is one of the largest scientific virological and biotechnological centers in Russia.

HIV patients lose immunity to smallpox even though they were vaccinated against the disease as children and have had much of their immune system restored with antiretroviral therapy, according to a study published in the Journal of Infectious Diseases. Called HIV-associated immune amnesia, the finding could explain why people living with HIV still tend to have shorter lives on average than their HIV-negative counterparts despite being on antiretroviral therapy. The study follows other research recently published in the journals Science and Science Immunology that found the immune systems of children who contracted measles similarly "forgot" their immunity against other illnesses such as influenza.

Mark K. Slifka, Ph.D., a professor of molecular microbiology and immunology at the Oregon Health & Science University School of Medicine and Oregon National Primate Research Center, led the study. Slifka and his colleagues compared the T-cell and antibody responses of a total of 100 HIV-positive and HIV-negative women who were vaccinated against smallpox in their youth. The research team chose smallpox because its last known U.S. case was in 1949, meaning study subjects haven't recently been exposed to its virus, which would have triggered new T-cell and antibody responses. They found the immune systems of HIV-positive women who were on antiretroviral therapy had a limited response when their blood was exposed to the vaccina virus, which is used in the smallpox vaccine. Normally, those vaccinated against smallpox have CD4 T cells that remember the virus and respond in large numbers when they're exposed again. Previous research has shown smallpox virus-specific CD4 T cells are maintained for up to 75 years after vaccination. This finding happened despite the fact that antiretroviral therapy works by boosting CD4 T cell counts in HIV-positive patients. This indicates that while antiretroviral therapy may boost total T cell counts overall, it can't recover virus-specific T cells generated from prior childhood vaccinations. Slifka and his colleagues plan to evaluate whether the same phenomenon occurs in HIV-infected men, and if people living with HIV also lose immune memory to other diseases.

Published in J. Infectious Diseases(23 December 2019):

https://doi.org/10.1093/infdis/jiz678