Simple, easy and effective COVID pills are hitting California pharmacies, offering hope as cases soar and immunity wanes.
But powerful new drugs – Pfizer’s Paxlovid and Merck’s molnupiravir – are in short supply, forcing doctors to make tough choices about who will benefit most from treatment.
There is a second challenge: the pills must be taken within five days of the onset of symptoms when the virus is still reproducing. This means that it is important to find a test, pronto.
“The trick is quick,” said Dr. Walter Newman of San Jose, medical director for the United Farmworkers Union. This week, he prescribed the pills to two newly infected patients who were at risk for severe COVID-19 due to their age and diabetes.
As more than 100,000 Californians are infected every day, “we’re inundated,” he said. “This will prevent mild or moderate cases from progressing to severe illness and death.”
Dana Ludwig acknowledged her ailing 86-year-old brother-in-law, visiting from Huntington Beach, faced potential danger.
In just three hours, doctors at UC San Francisco’s dedicated COVID emergency room provided a PCR-confirmed diagnosis — and a prescription. Now, after four days of treatment, her severe cough persists but her temperature has stabilized.
“He now has a better chance of surviving this thing,” said Ludwig, a data scientist who lives in Berkeley. “Even though he looked good, he could have gone down in a week.”
The U.S. Food and Drug Administration cleared both drugs in late December — just as antibody levels in vaccinated Americans were dropping and the highly contagious omicron variant began to overtake the delta.
Antiviral drugs are designed to turn life-threatening COVID-19 infections into a nuisance. Patients simply pick up the drug from a pharmacy, like any other prescription.
“We are currently struggling to treat COVID, due to the limited treatments we have,” said Deepak Sisodiya, director of pharmacy services at Stanford Health Care. “And with oral therapies, patients don’t have to come. They can be taken home.”
By preventing serious diseases, this approach is “a game-changer. It really helps protect our hospital resources,” said UCSF infectious disease expert Dr. Peter Chin-Hong.
Scientists emphasize that vaccines remain the best line of defense as they reduce the risk of infection and the impact if you get sick. But to save the unvaccinated and those with “breakthrough” cases, they recognized they needed a drug that could help people who were already sick.
The pills come at a time when some of the traditional tools for fighting the virus – called monoclonal antibodies – are losing their effectiveness. Antivirals are easier to take than monoclonals because they don’t require an intravenous infusion.
And unlike vaccines or monoclonals, drugs do not create protective antibodies. Instead, they attack the virus itself.
Pfizer’s drug blocks an enzyme the virus needs to reproduce. Merck’s drug also stops viral replication, but in a different way. It is based on a fake version of the virus’s genetic material; when the virus multiplies, it dies.
Results from clinical trials have been encouraging. The Pfizer drug reduces the risk of hospitalization or death in high-risk adults by 89%. Merck’s drug is significantly less effective, reducing hospitalizations and deaths by 30%.
They work against all current variants. And although there is a risk of interaction with other medications, there are few side effects.
Both drugs are given for five days. Pfizer’s three-tablet regimen is taken in the morning and evening. Merck is four capsules, twice a day.
But there is a shortage, so they are only offered to people who meet these three criteria: positive test results, symptoms of mild to moderate COVID-19 illness, and high risk of progression to severe illness.
“The provider does the clinical assessment,” Sisodiya said. “When supply doesn’t meet demand, how do you make those tough choices? Our approach at Stanford was very intentional. We (classify) patients according to risk.
The highest priority goes to people who are unvaccinated, partially vaccinated or vaccinated but immunocompromised due to disease or age, doctors said. Priority is also offered to people with cancer, cardiovascular disease, chronic kidney disease, chronic lung disease, diabetes, obesity, pregnancy and sickle cell disease.
“We all have patients we’d like to treat, but we just can’t, depending on our supply,” said Katherine Yang, infectious disease pharmacist at UCSF Health.
Why are there so few offers?
Mass production of small molecule drugs is logistically complicated, according to medicinal chemist Derek Lowe in the journal Science. Medicines are produced from a wide variety of chemicals, called reagents, which are sourced from overseas suppliers, mainly in China. And the production must be done on an industrial scale. For example, making 10 million layers of Paxlovid requires about 16.5 tons of material, he estimates.
“There is a shortage of what is used to make things,” he wrote. “That’s how it goes in the fine chemicals business – there’s a compound that nobody really cares much about – until they do.”
Federal decision-making is also blamed for the shortage. At first, the United States did not place orders for the mass production of pills, as it did for vaccines, said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute in La Jolla. .
When the pill showed great promise, “Pfizer contacted the administration and said, ‘Do you want to place large orders for Paxlovid? said Topol. Trusting in the power of vaccines, “he declined”.
The federal government is now working with businesses to stimulate manufacturing. But it takes six to eight months to make the Pfizer pill. Merck’s pill is easier to produce. The United States bought enough Paxlovid to treat 20 million people; 10 million are currently being distributed, with 4 million courses available at the end of January and another 10 million to come in June. It pledged to buy enough molnupiravir for 3.1 million people.
Distribution to states is based on population. This week, the federal government sent California 9,560 of its 99,960 courses of Paxlovid and 38,480 of 399,920 courses of molnupiravir.
Then, California distributes it among the counties, based on a different formula: equity and number of cases. This means, for example, that hard-hit Riverside County gets far more medicine than Marin.
So far, Bay Area counties have only received enough treatment for a few thousand patients.
Each county decides which of its hospitals, health centers and pharmacies receives the drug, and how many. Deliveries come directly from Pfizer and Merck. But supply is not keeping up with demand, UCSF’s Yang said.
“It’s very dynamic. … Part of the difficulty for providers is trying to find a pharmacy that actually has it in stock,” she said. “We’ll take whatever we can.”
Here’s a look at the Bay Area’s current supply of coveted antiviral drugs that treat COVID-19:
- Santa Clara County: 200 of Paxlovid and 920 of molnupiravir;
- San Mateo County: 60 Paxlovid, 320 molnupiravir;
- Contra Costa County: 120 paxlovides, no molnupiravir yet;
- Santa Cruz County: 20 Paxlovid, 280 molnupiravir;
- San Francisco County: 100 Paxlovid; 500 molnupiravir, of which 160 have been received;
- Alameda County did not provide data but said Paxlovid “is in high demand and in short supply” and there is no molnupiravir yet.
The list of state antiviral providers can be viewed here: https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/Antiviral-Therapeutics.aspx. This does not guarantee availability.