5 FDA-approved antivirals could target COVID-19

The virus that causes COVID-19, SARS-CoV-2, cannot grow and spread through the body without the help of a protein called polymerase. Now researchers at Columbia University and the University of Wisconsin-Madison have identified several molecules that interfere with the polymerase reaction—and some of them are already FDA-approved to treat other viruses.

The researchers identified five existing drugs that can shut down the polymerase reaction, they reported in the journal Antiviral Research. They include medicines used to treat HIV, cytomegalovirus, and hepatitis B.

SARS-CoV-2 uses polymerase to copy its genome inside of infected cells. But if that process could be stopped, the immune system would kick into gear and destroy the coronavirus, the researchers reasoned.

The team started their quest to interrupt the polymerase reaction by investigating an active ingredient of Gilead’s hepatitis C blockbuster Sovaldi. They analyzed a triphosphate that had been shown in previous experiments to halt the polymerase reaction of SARS-CoV-2, which sparked an outbreak in the early 2000s.

From there, they selected 11 compounds that they thought would have the best features to inhibit the polymerase of SARS-CoV-2. All but three did the job, they reported.

The five FDA-approved drugs that could work against COVID, the team reported, include ViiV’s Ziagen and Bristol Myers Squibb’s Zerit, both used to treat HIV; Roche’s Valcyte and Gilead’s Vistide for cytomegalovirus; and BMS’ Baraclude for hepatitis B.

In the search for COVID-19 remedies, several researchers and biopharma companies have drawn inspiration from previous studies of the first SARS virus. They include Ridgeback Biotherapeutics, which is testing its antiviral, EIDD-2801, in both hospitalized and non-hospitalized COVID patients. EIDD-2801 has shown activity against other RNA viruses, including SARS and MERS.

Gilead’s remdesivir, already FDA-approved to treat COVID-19, was originally being studied to treat hepatitis C (HCV) and respiratory syncytial virus (RSV). Other companies that are repurposing drugs initially developed against other diseases are Pinpoint Therapeutics and Orpheris.

The next step for the Columbia and University of Wisconsin researchers is to perform cell-culture studies to demonstrate the potency of the five FDA-approved antivirals against COVID-19. From there, the most effective of the drugs—or modified versions of them—could advance to further studies, they suggested.

https://www.fiercebiotech.com/research/five-fda-approved-antivirals-could-target-covid-19-study

As Covid cases spike, California pauses multimillion-dollar testing expansion

In April, California Gov. Gavin Newsom launched a multimillion-dollar state initiative to bring COVID-19 testing to the people and places with the least access: rural towns and disadvantaged inner-city neighborhoods.

California is now halting its expansion, citing costs, even as the state is getting walloped by record-setting spikes in new infections and double-digit increases in hospitalizations.

The state will no longer fund new testing sites despite pleas from counties for additional assistance—and it has closed some locations and moved them elsewhere. It also has threatened to pull testing out of underused sites, according to nearly two dozen interviews with county public health officials.

While it’s early, some winners and losers have emerged: El Dorado County, east of Sacramento, lost its testing site in the town of Shingle Springs in June because it couldn’t fill enough appointment slots, while Fresno County gained a site that had been pulled from elsewhere, said its health officer, Rais Vohra, M.D.

Yet San Mateo County has asked state officials three times for a second state-funded testing venue to address testing gaps in Black and farmworker neighborhoods, but has been “told no, repeatedly,” said Justin Mates, deputy county manager. So the county transformed its sole state site into a roving testing unit.

“Equity is certainly a concern for us,” Mates said. “We really need help with testing access if we’re going to reach our Latino residents and places like East Palo Alto,” a diverse city whose population is mainly Latino, African American and Asian/Pacific Islander.

California has committed up to $132 million in contracts with two private COVID-19 testing companies, Verily Life Sciences and OptumServe, to offer free coronavirus tests at more than 100 sites that the Newsom administration has identified as “testing deserts.” The expansion has dramatically increased the state’s overall testing numbers, which swelled from 16,000 tests per day in April to 105,000 on Monday.

Testing is also available at county-funded locations, private pharmacies, hospitals and community clinics.

State Health and Human Services Secretary Mark Ghaly confirmed that the state is pulling sites out of counties that aren’t generating high enough numbers and cutting off funding for new locations.

“With every asset and resource—especially when it’s scarce—you want it to go to places where it’s most needed,” Ghaly said. “It wouldn’t be prudent or wise to maintain spending in a place where resources aren’t being used.”

Newsom himself has voiced concern about the price tag, given “unprecedented” budget shortfalls. “There is a big cost associated with testing,” he said in late June.

A Newsom administration official confirmed the state wants to see counties fill at least 80% of testing slots at each location. And if testing drops below 50% for a few days or longer, counties are warned the sites could be transferred elsewhere.

Counties argue there’s a public health benefit to keeping underperforming locations open—simply to ensure that testing is available to rural and disenfranchised communities. Across the state, they are fighting to save state-funded sites even as they are being overwhelmed by rising coronavirus cases linked largely to social gatherings.

“It’s how we are able to quickly identify where the virus is and if there are hot spots,” said Olivia Kasirye, M.D., health officer for Sacramento County, where holiday celebrations and booze-fueled gatherings among family and friends are sending infection rates soaring.

Contra Costa County saw its testing numbers drop in June and was at risk of losing a state-funded site until it proved it could keep appointments near 80% of capacity, said its health officer, Chris Farnitano, M.D.

Riverside County was warned June 16 that a state-funded site north of Temecula would be “moved to another county” if it didn’t get its testing above 50%, according to an email from the state’s testing task force. The state told Mendocino County it could lose its state-funded site, the only free testing available within a two-hour drive for some rural residents, if it didn’t push numbers up.

Alameda County grew so frustrated with state requirements that it undertook a testing expansion of its own.

“We realized we couldn’t depend on the state, especially to reach our vulnerable communities,” said Jocelyn Freeman Garrick, M.D., an emergency room doctor at Highland Hospital in Oakland, who is leading the county’s testing task force.

El Dorado County, which lost its site, so far has maintained a relatively low count of COVID-19 cases. It can’t afford to replace the site but will “make do,” said county spokesperson Carla Hass.

Ghaly said the state is working with counties in danger of losing sites to give them a chance to fill testing slots. State officials declined to say how many counties have lost sites, but as new infections have soared, testing numbers are starting to pick back up. The list of counties at risk of losing a site has dwindled from around a dozen in early June to a few last week.

Public health experts say focusing so intently on testing numbers, and not on adequately testing in Black and Latino neighborhoods, risks abandoning communities that already face immense barriers to health care like racism and poverty.

“If you ignore these communities, then we’ll keep seeing the kinds of surges that we’re seeing now,” said Tony Iton, M.D., formerly the top health official for Alameda County and now a senior vice president of the California Endowment, which is working with counties to expand testing in underserved neighborhoods.

Entrenched socioeconomic barriers also make it difficult to get, and keep, testing numbers up. For instance, people who want to be tested at state sites often need internet access and an email address. Most are drive-thru, requiring access to a vehicle.

Many low-income people can’t meet those requirements, and undocumented immigrants fear that providing personal information to obtain a test could expose them to immigration officials, said Marty Fenstersheib, M.D., a former health officer of Santa Clara County who is leading its testing program.

“We can have all the tests we want, but if people are afraid to come and get tested, it’s not going to be of any benefit,” he said.

State contracts funding the testing sites were extended this month but are set to expire Aug. 31, and administration officials have not told counties whether the state will continue funding them after that, said Mimi Hall, president of the County Health Executives Association of California and director of public health for Santa Cruz County.

Counties can’t afford to keep the sites running, said Hall, who is on the state’s testing task force.

“It’s hard to plan when we don’t know how long we’ll be able to keep them,” Hall said.

https://www.fiercebiotech.com/medtech/as-cases-spike-california-pauses-multimillion-dollar-testing-expansion

Tamping down stroke damage with a drug that protects brain cells

For patients who have suffered strokes, clot-busting drugs and surgery can help in their recovery by restoring blood flow to the brain. But no FDA-approved drug is available to reduce the loss of neurons that often leads to long-term disabilities.

Neuroscientists at the University of Pittsburgh have identified a novel drug they believe could protect the brain from neuronal tissue damage during and after a stroke.

The drug, called TAT-DP-2, works by disrupting a potassium ion channel that’s key to regulating neuronal death. In mice, administering the drug after stroke led to reduced brain damage, according to a new study published in the journal Science Advances.

A stroke happens when clots block a blood vessel in the brain, which prevents oxygen from reaching neurons. A region of the brain called the ischemic penumbra becomes dysfunctional, and tissues there often die later.

“We are looking for ways to prevent these other neurons from dying,” explained Elias Aizenman, Ph.D., senior author and professor of neurobiology at the University of Pittsburgh, in a statement. “If we can do that, recovery might be improved, and we might be able to better help people who have strokes in which the clot is in an inaccessible blood vessel or who could not get to the hospital in time for early intervention.”

In previous studies, Aizenman and colleagues found that a potassium channel in the cell membrane called Kv2.1 works with a protein called syntaxin to rally additional channels into the plasma membrane hours after a stroke. That prompts potassium ions to leak out of the neurons, leading to cell death.

The scientists figured that disrupting the clustering of these channels could promote the protection of neurons. Following that rationale, they designed the injectable TAT-DP-2 to do just that.

In lab dishes, adding TAT-DP-2 to neurons following injury significantly reduced enhancement of Kv2.1 potassium currents and resulted in less cell death.

In mice, animals that received TAT-DP-2 after a stroke had smaller areas of stroke damage, and they performed better on a neurological function score after a long-term follow-up than did control mice, the team reported.

Millions of people suffer from a stroke annually. While existing therapies and medical procedures can provide benefits, many patients still don’t survive or they suffer serious long-term symptoms like swallowing difficulties and numbness. That’s why scientists are still looking for better options to manage stroke.

A research team at Lund University in Sweden recently turned skin cells into nerve cells, which helped repair the neuronal damage caused by strokes in mice. Stanford University scientists previously showed that blocking a microRNA called miR-181a after brain trauma prompted star-shaped astrocytes to turn into neurons.

The University of Pittsburgh scientists argued that their findings suggest disruption of Kv2.1 could be a viable neuro-protective strategy and that it could guide the development of novel stroke drugs.

https://www.fiercebiotech.com/research/reducing-stroke-damage-a-new-drug

Fujifilm joins Dr. Reddy’s, Global Response Aid to make Covid drug Avigan

Meeting global demand for a potential COVID-19 treatment is more than any one company can handle on its own. Acknowledging that reality, Japanese drugmaker Fujifilm has picked partners for its offering.

Fujifilm has struck a three-way deal with India’s Dr. Reddy’s Laboratories and Dubai-based Global Response Aid to manufacture and sell its flu drug Avigan (favipiravir) for potential treatment of COVID-19, the company said Wednesday.

The drug is already approved for COVID-19 in India and Russia. The new agreement covers all countries other than Japan, China and Russia.

Specifically, for an unidentified lump-sum license fee and royalties on sales, Fujifilm is granting Dr. Reddy’s and GRA access to Avigan’s preclinical and clinical data to help run their own studies. Dr. Reddy’s gains exclusive rights to the drug in India.

In addition, Fujifilm will transfer its manufacturing method exclusively to Dr. Reddy’s, which will establish production of the drug and utilize GRA’s global sales network to supply the med.

Avigan was originally developed against influenza pandemics. It gained global attention when Japanese Prime Minister Shinzo Abe touted it as a potential COVID-19 treatment.

With that government support, a fast-track approval in Japan was initially expected in May. But clinical research on the drug suddenly slowed down as COVID-19 cases dropped in Japan. A month ago, Nikkei Asian Review reported that completion of the trial would instead come in July at the earliest, as it has only hit around 70% of the enrollment goal.

Back in April, amid speculation around Avigan’s potential in COVID-19 and its side effects, including birth defects, Fujifilm said it would increase monthly production of Avigan up to 100,000 treatment courses by July, about 2.5 times more than its level at the beginning of March.

On June 20, India’s Glenmark Pharmaceuticals won a local go-ahead to market a generic version of Avigan, which it’s selling under the brand FabiFlu, for the treatment of mild to moderate COVID-19 patients.

Meanwhile, Gilead Sciences has also signed on multiple partners for FDA-authorized COVID-19 drug remdesivir, including India’s Cipla and Hetero Labs and Jubilant Life Sciences.

https://www.fiercepharma.com/manufacturing/fujifilm-pairs-dr-reddy-s-global-response-aid-to-make-covid-19-drug-avigan

Minnesota governor blasts drug industry group PhRMA for insulin pricing lawsuit

Amid congressional gridlock on drug prices, some states have taken matters into their own hands. That’s the case in Minnesota, where activists and officials lauded the passing of the Alec Smith Insulin Affordability Act.

But on the eve of a Wednesday press conference celebrating the bill becoming law, PhRMA sued. The industry trade group is seeking a court’s declaration that the law is unconstitutional and a permanent injunction barring its enforcement.

The act, which Gov. Tim Walz signed Wednesday, provides relief to diabetes patients who are unable to afford their insulin, offering an “urgent” 30-day supply for a copay of up to $35. It also provides a year of insulin to eligible patients for no more than $50 per 90-day refill.

The law was the result of a compromise with the industry, Walz said at a press conference celebrating its signing. He “never heard a word” that the industry would sue.

“I gotta be honest, they did something I didn’t think was possible,” he said. “They’re more hated than COVID-19.”

The law is named after a diabetes patient who died after rationing his insulin, Walz said. His family and others were in attendance at the Wednesday press conference.

For its part, PhRMA says the act violates the Fifth and Fourteenth Amendments to the U.S. Constitution, which prohibit the state from “taking manufacturers’ private property for public use without just compensation.”

PhRMA general counsel James Stansel said in a statement the “law is unconstitutional, overlooks common-sense solutions to help patients afford their insulin and, despite its claims, still allows for patients to be charged at the pharmacy for the insulin that manufacturers are required to provide for free.”

In response to the suit, Minnesota Lt. Gov. Peggy Flanagan said Wednesday the industry “may continue fighting, but so will we.”

“And we have the advantage of being right,” she added.

The lawsuit comes as the pharma industry has enjoyed a boost to its reputation due to its response to the COVID-19 pandemic. But the episode clearly illustrates that drug prices are still an important issue in America, and that the industry stands to face intense criticism when it pushes back against affordability measures.

https://www.fiercepharma.com/pharma/they-re-more-hated-than-covid-19-minnesota-governor-blasts-phrma-for-insulin-pricing-lawsuit

Alabama students attend ‘COVID-19 parties,’ gamble on who gets sick first

Students in Tuscaloosa, Alabama, are reportedly throwing “COVID parties” with their friends and gambling on who will get sick first, according to local officials.

City council member Sonya McKinstry testified Wednesday that a series of previously reported parties were all part of a morbid game that included intentionally inviting COVID-positive students in an attempt to intentionally contract the deadly virus.

“They put money in a pot and they try to get COVID. Whoever gets COVID first gets the pot. It makes no sense,” she said.

City council members did not mention the University of Alabama by name, but the school is the largest college in the city and the flagship school of the state’s university system.

Tuscaloosa City Fire Chief Randy Smith briefed the council on these parties earlier this week, saying that authorities thought students’ intentional gambling on virus transmission “was kind of a rumor at first,” but added, “We did some additional research … not only did the doctors’ offices help confirm it but the state confirmed they also had the same information.”

Despite the news, McKinstry insists the city is taking the public health threat of coronavirus seriously.

“We’re trying to break up any parties that we know of,” she told ABC News.

There have been at least 37,536 recorded coronavirus infections and 926 fatalities in Alabama.

https://nypost.com/2020/07/02/alabama-students-gamble-on-who-gets-sick-at-covid-19-parties/