The story of what might become the next major breakthrough in Covid-19 treatment starts on a hotel hallway floor in January 2020, months before you were worried about the virus, weeks before you likely knew it existed. A scientist and a business executive were at a health-care conference in San Francisco, hatching a plan to get a promising drug out of academia and into research trials for regulatory approval. George Painter, president of the Emory Institute for Drug Development, and Wendy Holman, chief executive officer of Ridgeback Biotherapeutics, had met at the Handlery Union Square Hotel to discuss a compound Painter had started developing with funding from the National Institutes of Health. They got so enthusiastic about the possibilities that their meeting ran long and a group of lawyers kicked them out of their room. So they continued on the hall floor, hours after they’d started.
Painter and Holman weren’t talking about targeting Covid at the time. The disease and the coronavirus that causes it, SARSCoV-2, weren’t major concerns at the J.P. Morgan-run conference, where handshakes and cocktail parties with hundreds of guests were still the norm. Rather, Painter was hoping his drug, molnupiravir, could get more funding to speed up flu studies. Holman was eager to see if it worked on Ebola. That’s the thing about molnupiravir: Many scientists think it could be a broad-spectrum antiviral, effective against a range of threats.
A few days later, Holman arrived in Atlanta to see the labs at Emory and pore through the early data. As she and Painter hashed out the terms of a deal in which Ridgeback would buy the drug and start studying its safety and efficacy in people, Covid was seeping into the public consciousness. By the time Ridgeback announced its acquisition of molnupiravir, on March 19, the world had shut down, and it was clear which threat the drug needed to be tested on right away. Clinical trials for the pill kicked off in April. The next month, Merck & Co., which has a deep history of public- health development work, including on HIV and Ebola, struck a deal to buy molnu piravir from Ridgeback and start the types of large-scale trials that could get it authorized by regulators. Those began in the fall.
Even as vaccines are rolling out worldwide, the corona virus and its mutations still pose a major health threat. Not everyone who’s eligible for a shot will agree to get one. The hundreds of thousands of people who continue to contract Covid each day have few treatment options. There’s no simple, inexpensive pill that can prevent those at the earliest stages of infection from later needing to be hospitalized. The monoclonal antibody therapies that doctors now have available for those most at risk of getting severely ill need to be administered by infusions at specialized medical centers. And for those who do become hospitalized, the antiviral remdesivir, from Gilead Sciences Inc., speeds recovery, but hasn’t been shown to reduce deaths.
Drugmakers see an opportunity to add to the arsenal of potential therapies. There are 246 antivirals in development, according to the Biotechnology Innovation Organization, an industry trade group. And companies as big as Pfizer Inc. and as little-known as Veru Inc. are testing them in pill form. Merck’s molnupiravir is among the furthest along. Its developers hope the pills can be prescribed widely to anyone who gets sick. Think Tamiflu for Covid.
The hurdle, beyond ensuring the drug works, is making sure it’s safe. Developers of antivirals have been dealing with the thorny issues they pose for decades. Should Merck succeed in demonstrating that molnupiravir is effective and free of serious side effects, it could be a boon to the company, and to society, for many years to come.
Viruses are uniquely difficult to attack with drugs. They hijack human cells and set up machinery to churn out copies of themselves, creating a challenge: destroying the virus without harming the cells. Success, when it comes, can be fleeting, because viruses mutate to survive.
The first anti viral approved in the U.S. was idoxuridine, a herpes treatment regulators green-lit in 1963, generations after the discovery of anti biotics. It’s among a widely used class of drugs called nucleoside analogues— synthetic versions of nucleosides, critical building blocks of DNA and its counterpart, RNA, the messenger molecule that delivers instructions to a cell’s protein-making factories. Nucleoside analogues prevent viruses from replicating, or from replicating effectively, inside cells.
Concerns that idoxuridine was toxic to the heart led it to be recommended only for topical use—the sort of hurdle that kept antiviral drug development slow. The AIDS crisis of the 1980s invigorated the field. “Until HIV came along, there were precious few antivirals,” says Saye Khoo, a professor of pharmacology and therapeutics at the University of Liverpool. Rising death rates and the public outcry about the virus prompted companies and governments to pour millions of dollars into an area that hadn’t seen that kind of investment before.
The breakthroughs were meaningful. Khoo says scientists discovered that some people appeared to have a natural resistance to getting HIV—they lacked a receptor allowing the virus to enter cells—leading to a new class of drugs. They also realized that antivirals would need to be adaptable enough to deal with mutations, and that potent combination therapies involving multiple drugs could prevent the evolution and spread of drug resistance. At the same time, some of the new treatments had serious side effects, including anemia and liver problems, pushing drugmakers to continually improve upon their treatments.
During this era, the U.S. government also started to boost its pandemic preparedness, with an emphasis on guarding against bioterrorism. President Bill Clinton, alarmed after reading the Richard Preston novel The Cobra Event, in which a terrorist unleashes a virus that causes a fictional ailment called brainpox, convened a group of cabinet members and scientists in April 1998 to assess such threats. That led to the formation of what’s now called the Strategic National Stockpile, whose objective was to have enough emergency medicines and materials to deploy within 12 hours of an official request in times of crisis. Following the Sept. 11 and anthrax attacks of 2001, the Bush administration directed the stockpile to procure products such as smallpox vaccines. Then, in 2006, Congress authorized the formation of the Biomedical Advanced Research and Development Authority, or Barda, to help develop treatments and vaccines for public-health threats.
Pharma’s next major advance in antivirals came in 2013, a $1,000-per-pill hepatitis C cure produced by Gilead. The company was roundly criticized for setting so high a price for such a widely used drug. It was the usual risk- reward problem: If pharma companies can’t command prices that allow them to profit from the drugs, they aren’t likely to invest in them.
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