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UCSF Team Finds Cancer Drug That Is 30 Times More Effective At Fighting COVID Than Remdesivir – SFist

A research team at UCSF has landed on a potential game-changing treatment for COVID-19, though it is a cancer drug made by a Spanish firm that is not yet approved for any uses in the United States.

The drug is called Aplidin (generic name: plitidepsin), and it’s a compound that was originally derived from one found in a bizarre marine creature found near Ibiza called Aplidium albicans. As the team explains in a new report in the journal Science, plitidepsin was shown to dramatically inhibit the replication of SARS CoV-2, a.k.a. the coronavirus, and may in fact be 30 times more effective as an antiviral treatment than remdesivir, which has been used on an emergency basis in patients in clinical settings since last winter.

The team that discovered the new treatment was led by UCSF systems biologist Nevan Krogan, and it appears to potentially be the biggest success to arrive from a project that began last February to isolate existing drugs and compounds that might work as antiviral treatments. As we reported last May, Krogan’s team at the Quantitative Biosciences Institute at UCSF dropped everything they were working on last winter to focus on COVID-19, and by April they had identified 10 existing drugs that showed promise at treating the new disease.

Scientists both in San Francisco and on other teams around the globe participating in the same effort found two human proteins that appeared to be key in the fight to shut down the coronavirus’ ability to replicate inside people, Sigma R1 and Sigma R2, and their drug search initially focused on these. Aplidin works on the human protein known as eEF1A, and because it focuses on the human part of the equation and not the virus, it should hopefully remain effective as the virus mutates.

And the project is highlighting something scientists have long stressed about the importance of maintaining biodiversity in the world’s oceans and elsewhere. The marine invertebrate from which this compound is derived is an ascidian or sea squirt that looks “a bit like a disembodied brain,” as the Chronicle explains. The drug is actually owned by a Spanish company founded by a scuba diver, Pharma Mar, and it’s been approved in Australia for treating the blood cancer known as multiple myeloma. It’s also been used in the EU as a treatment for lymphoblastic leukemia.

The drug is in Phase 2 clinical trials in Spain, during which it has been tested on 45 severely ill COVID patients. Based on data on the first 27 of those patients, the drug significantly reduced the amount of time people spent in the hospital, with 81 percent going home after 15 days, compared to a typical rate of under 50 percent. And according to a separate paper, Aplidin appears to be effective against the UK variant of the virus as well.

“We need some new weapons in the arsenal,” Krogan tells the Chronicle. “This is by far the best thing we’ve seen.” Krogan says the team researching this drug was also led by virus expert Adolfo García-Sastre, based at the Icahn School of Medicine at Mount Sinai Hospital in New York.

UCSF infectious disease expert Dr. Peter Chin-Hong says that if the drug emerges from a Phase 3 trial still looking good, it’s likely it will be part of a “cocktail” of therapies for COVID. Already doctors across the country are treating patients with a cocktail of remdesivir and the steroid dexamethasone, and in Australia, Aplidin is used in combination with dexamethasone to treat multiple myeloma.

Aplidin still has to undergo more broad-based Phase 3 clinical trials, which will reportedly take place in both Spain and the U.S. And it remains to be seen how long it could be — should it prove as effective as the early trials suggest — before the drug becomes widely available here.

Top image: An image of the sea squirt Aplidium albicans found in the Balearic Islands, from which the synthetic drug Aplidin is derived. Photo via Pharma Mar

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