Focus on antivirals and vaccines as monkeypox continues

Focus on antivirals and vaccines as monkeypox continues

Since the first monkeypox case emerged on May 6, outbreaks of the disease have been reported from several countries, with the United Kingdom, Spain and Portugal at the fore, followed by Canada, Israel and Australia, among others. The United States has reported cases in Boston and New York, and presumptive cases have occurred in Utah and Florida. As of May 25, nearly 350 cases, either suspected (83) or confirmed (265), have been reported globally.

Outbreaks of monkeypox were previously confined to Central and West Africa, with the exception of an impressively large outbreak in the United States in 2003, in which 47 people were infected in six states. The epidemic was traced to the Gambian rat, cord squirrels, and flowers imported from Ghana as pets that infected prairie dogs at a large pet wholesale store.

Dr. Dennis Hrubi

“It’s amazing how many of these viruses – COVID, now monkeypox and others – [exist]. They’re out in the wild in the animal’s tank, said Dennis Hruby, PhD, executive vice president/chief scientific officer and founder of SIGA Technologies.

“When it comes to human populations, they sometimes behave in ways that we wouldn’t expect,” he said. “That’s in addition to some mutations that alter those strains and pathogens and can become epidemic.” Medscape Medical News.

Now that the virus is a pandemic, there is urgent interest in drugs and vaccines that may stop its spread.

smallpox drug ticofermat

SIGA’s drug is tecovirimat, initially known as ST-246 and now classified as TPOXX. The U.S. Food and Drug Administration (FDA) approved an oral preparation for treating smallpox in 2018. And while smallpox was eradicated by 1980, there were continuing concerns about its potential use in a bioterrorist attack.

Tecovirimat is also approved for smallpox in Canada. In Europe, approval includes treatment of monkeypox, cowpox, and complications of lactation immunization. On May 19, the U.S. Food and Drug Administration approved an IV formula of tekovirimat for those unable to tolerate oral medications.

In a press release, SIGA noted that this technology was “developed through funding and collaboration with the Biomedical Advanced Research and Development Authority (BARDA) at the US Department of Health and Human Services, as well as early development with support from the National Institutes of Health, the US Centers for Disease Control and Prevention [CDC]and the Ministry of Defense. Ticofirim is stockpiled by the US government to mitigate the impact of a potential outbreak or bioterrorist attack.”

SIGA adds that, under Project Bioshield, “the United States maintains an inventory of 1.7 million courses in the Strategic National Stockpile.” The drug is only available through government stock.

Tecovirimat works by preventing viruses from reproducing by interfering with a protein, VP37. Harubi explained that the virus cannot escape from the cell and therefore cannot infect other cells.

Tecovirimat was developed under the so-called animal rules of the Food and Drug Administration, which allow approval on the basis of animal studies when studies of human efficacy are unethical or impractical.

In the placebo-controlled human pharmacokinetic and safety study, only 2% of 359 who received TPOXX had discontinued treatment due to adverse reactions, a rate similar to placebo. The most common reactions (2%) were headache, nausea, and abdominal pain. Significant drug interactions have been found with the co-administration of repaglinide and midazolam.

It should be noted that the efficacy of tekovirimat may be reduced in immunocompromised patients. Smallpox vaccine is contraindicated for immunocompromised persons. These people should be offered the vaccine immunoglobulin.

With monkeypox, “the earlier the disease is recognized and treatment started, [the] “It’s much more effective,” Kharroba said. “In the monkey model that’s very similar to humans, if we treat early when the first lesions appear or even several days after the lesions appear, we see close to 100% protection.”

Another alternative drug for smallpox and (potentially) monkeypox is brinkidofovir chimerix (BCV, Tembexa), a lipid compound of cidofovir, an anti-CMV drug. Brincidofovir has a better safety profile than cidofovir and has also been approved under the Animal Law.

Until now It is suggested that tekovirimat is the drug of choice for monkeypox. They noted that for severely infected patients, it could be combined with brincidofovir after consultation with the CDC or state health department officials.

There are two vaccines available

Two vaccines are currently available. The oldest is ACAM2000, a replication-effective vaccine that replaced Dryvax, which was discontinued in 1977, the last year cases of smallpox occurred naturally. ACAM2000 is used to immunize military recruits. It was produced by Sanofi and is now produced by Emergent Biosolutions. Being a live vaccine, it is contraindicated for immunocompromised or pregnant persons, as well as for children and those with eczema, due to the occurrence of dangerous and sometimes fatal reactions. Because of unexpected cardiac complications in first responders who received Dryvax, a history of heart disease or significant risk factors is a contraindication to replication-specific (live) vaccination except in the event of bioterrorism.

ACAM2000 is not FDA approved for monkeypox, but it is readily available. In the United States, the US stockpile contains more than 100 million doses, according to the Centers for Disease Control and Prevention.

Dr. Melvin Sanikas

“ACAM is not much different from Dryvax in terms of its safety profile,” Melvin Sanikas, M.D., who specializes in vaccines and health educationTell Medscape Medical News.

A newer option is a modified replication-deficient Ankara vaccine called Jynneos in the United States (Imvanex in Europe; Imvamune in Canada). The vaccine is made by Denmark-based Bavaria Nordic. Jynneos was approved by the FDA in 2019. It is also available through BARDA Stocks; 1000 doses available now and more on order.

In the current outbreak of monkeypox, Jynneos was shown to high-risk contacts in the UK. The CDC plans to make it available to high-risk contacts of infected people in the United States. This strategy is called “circular vaccination”, by which contacts are vaccinated only initially. The rings are then enlarged to include more people as needed. Circular vaccination works well with easily recognizable diseases such as monkeypox and in cases where there are few cases. It has been used very effectively for smallpox and Ebola.

Jynneos is not associated with the same risks as a live vaccine. In desired reactions, injection site reactions were common. Other systemic symptoms reported were muscle pain (42.8%), headache (34.8%), fatigue (30.4%), nausea (17.3%) and chills (10.4%).

Other vaccines are expected to be developed. Moderna just threw its hat in the ring, announcing that it had begun preclinical trials for monkeypox.

Prolonged close contact

Monkeypox is spread by large droplets, contact with infected lesions, or body fluids. It is believed to require close, long-term contact. In an e-mail interview, Sanikas said Medscape Medical News That “contact can be with (1) skin lesions of an infected person, (2) respiratory droplets on prolonged face-to-face contact, (3) cases in the UK in MSM, but this does not mean that the disease is now transmitted Sexually. People don’t need to have sex to get infected, but of course sexual intercourse means prolonged contact.” The transmission rate at home is less than 10%.

Sanikas emphasized that, as with smallpox, monkeypox could be transmitted by contact with contaminated clothing or bedding through contact with infected pests, with smallpox transmitted to Native Americans by colonists. Air transportation is a theoretical possibility but not considered a possibility. Being a DNA virus, monkeypox is less likely to mutate than COVID. “If it was contagious like the flu or coronavirus, there would have been more infections and outbreaks in countries where MPX is present. [monkeypox] It is endemic to West Africa or the Congo Basin.

Fortunately, this branch of monkeypox, which appears to have originated in West Africa, is estimated to have a mortality rate of about 1%. In contrast, the mortality rate in the clade of the Congo Basin reaches 10%.

Sanikas concluded, “Be careful, but there is no need for more fear and panic above what we have for COVID-19. Monkeypox is not COVID and will not cause the same devastation/death/lockdown as COVID-19.”

Hruby is an employee and shareholder of Siga. Sanicas reports no related financial relationships.

Jodi Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope, Triumphing Over Evil, and Conducting Clinical Research, the essential guide to the topic. You can find her at or on Twitter Tweet embed.

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2022-05-26 17:32:43

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