When the FDA in late December authorized two oral medications to treat early-stage COVID-19, the decision seemed like a Christmas gift for anyone living in fear of the virus.
The drugs have tremendous promise. A five-day course of the pills can prevent severe illness, potentially easing the burden on hospitals.
But, while manufacturing ramps up, the big worry was that providers would run out of the medications in the face of patient demand.
So far, that hasn’t happened. Instead, only 429 patients have received the drug in Massachusetts — using up just one-sixth of the available supply — as providers scramble to set up systems to manage distribution. Dispensing a sorely needed “game changer” drug, it turns out, can be quite complicated.
“I would have expected to run out quickly,” said Dr. Zandra Kelley, chief medical officer of the Greater Lawrence Family Health Center. By Friday afternoon, the clinic had dispensed just 15 courses of treatment, despite a concerted effort to connect with patients who have tested positive at the clinic and elsewhere.
Several obstacles stand between patients and the antivirals. In order for the pills to work, patients have to take them within five days of symptom onset, requiring fast action to identify those who could benefit and get the pills into their hands.
In addition, the patients must have symptoms — many of those who test positive do not — and they also must be at high risk of progressing to severe illness, which often means that they’re unvaccinated.
Adding to complications, these medications are not safe for everyone, so doctors need to take time checking patients’ medical histories.
”This is a medication that absolutely requires some clinical decision-making. It’s not something I would just hand out to people,” said Dr. Inga Lennes, senior vice president of ambulatory care and patient experience at Massachusetts General Hospital. “It requires clinicians to talk to the patient. … This is a 10- to 20-minute phone call.”
Dr. Kiame Mahaniah, chief executive of the Lynn Community Health Center, likened the logistics of antiviral distribution to “building a mini-public health system.”
Mahaniah said that in the Congo, where he grew up, the problem was a lack of resources. In Massachusetts, he said, “it’s really about coordination of access to resources.”
So far the Lynn clinic has dispensed antivirals to two patients. Others have called but many have been too far along in their illness. On a recent Saturday, a nurse practitioner held about 20 telehealth visits with COVID-19 patients, and none qualified for the medication.
The sprawling Beth Israel Lahey Health system had administered 16 doses of one antiviral as of Thursday morning, even though Dr. Richard Nesto, chief medical officer, said Beth Israel Lahey is “hellbent on making [the medications] as available as possible based on the supply.”
“This becomes a system challenge,” Nesto said. “It’s like a new program that’s being developed in real time in the middle of a pandemic.”
Health officials are also concerned about social and racial inequities. Many are striving to make sure that the minority groups hardest hit by the pandemic also have access to the treatments.
They have good reason to worry: A recent study showed that white people were more than twice as likely as Blacks to obtain an earlier COVID-19 treatment — monoclonal antibodies.
The federal government is buying the oral antiviral drugs and distributing them to the states. Each state then decides where the pills will go.
Massachusetts has been allocated 4,600 courses of oral antiviral treatment, each involving several pills taken twice a day for five days. Of these, the state has ordered and distributed 2,500. The pills have gone to 17 community health centers, several hospital systems, and a private company, Gothams, that has been running monoclonal antibody infusion sites for the state.
Those facilities have reported treating 429 patients as of Friday afternoon.
In Massachusetts, until supplies increase, a doctor can’t merely call the prescription into a pharmacy in the state for the patient to pick up, but must refer patients to a site that offers the medications.
Rhode Island, in contrast, reported 1,236 courses of treatment dispensed to patients as of Thursday. The state distributed the medications to nine pharmacies, as well as two health centers, the prison, and long-term care facilities. Mostly, individual physicians have been prescribing the drug and sending patients to one of the nine pharmacies.
Federal and state guidelines prioritize which patients should get the medications. At the top of the list are severely immunocompromised people, followed by people age 75 and older who are not fully vaccinated, and people 65 and older who are not fully vaccinated and also have a condition that puts them at risk.
Providers have to balance the individual’s circumstances with the options that are available. Two types of oral antivirals were approved in December.
Paxlovid, made by Pfizer, is considered the most effective, but is least available. It can be unsafe for patients with kidney or liver disease. And it interacts with a number of medications, including those commonly taken by the very people most at risk of severe COVID-19, such as anticoagulants, immunosuppressants, and anticonvulsants.
In some cases, patients can suspend their other medications during the five days that they’re taking Paxlovid, but many others are disqualified.
Instead, doctors may offer them molnupiravir, made by Merck. Molnupiravir is less effective at preventing hospitalization than Paxlovid. But it doesn’t interact with other drugs and doesn’t threaten the kidney or liver. There is, however, a risk of birth defects if taken by a woman in childbearing years or by a man who’s having relations with a woman who can become pregnant.
The Greater Lawrence Family Health Center has given out seven courses of Paxlovid and eight of molnupiravir. But several patients have turned down the medication, after learning that the FDA gave it an emergency use authorization rather than full approval. Because many eligible people are unvaccinated, those who rejected the vaccine are often equally wary of the medications, Kelley said. And since the medication is intended to treat early, mild COVID-19, by definition eligible patients don’t yet feel very ill, so they don’t always see the need.
In other cases, the health center has identified patients who tested positive but hasn’t been able to reach them within the five-day window, even though the clinic can deliver the medication.
In contrast, Mass General Brigham is finding widespread acceptance but struggles with supply. “Over 85 percent of patients we’ve offered molnupiravir have taken us up on it,” Lennes said. “The rate of accepting has been higher than we thought it would be.”
As for Paxlovid, the preferred drug, “With so few doses, it’s almost like we don’t have it,” she said.
Mass General Brigham, which has been allocated more than 3,000 doses, mostly of molnupiravir, has been sending the medications to its health centers in Charlestown, Chelsea, and Revere, communities hard hit by COVID-19. The health system is also treating patients through a central referral system, through which doctors can put patients in line for the medications.
About 30 to 40 percent of patients receiving the treatments at Mass General Brigham have not been vaccinated, and Lennes acknowledged that many clinicians are troubled to see a scarce resource allocated to people who declined to protect themselves with a vaccine. But they also believe it’s their job to take care of all patients. “I don’t see anger, I see more sadness. … that misinformation has really tangibly hurt patients,” she said.
Kelley, of the Lawrence clinic, pointed out that it benefits everyone to keep the hospitals from being overwhelmed, and the majority of hospitalized COVID-19 patients are unvaccinated.
Supplies of the antivirals are expected to increase this year, though most likely after the Omicron surge has ended. Merck expects to produce 10 million courses of treatment of molnupiravir this year. Paxlovid involves a more complex manufacturing process, and Pfizer projects making 30 million courses in the first half of the year and an additional 90 million in the final two quarters.
Among the 429 Massachusetts residents who received an oral antiviral treatment was Polonia Mendez Reynoso, an 82-year-old Haverhill woman who came to the Greater Lawrence Community Health Center on Jan. 18 with a sore throat so bad it was hard to swallow. A rapid test showed she had COVID-19. The nurse who delivered the news hugged her, and Reynoso cried, knowing the infection would mean she couldn’t see her family for some time.
Reynoso is fully vaccinated, including a booster, but she has high blood pressure and diabetes, which at her age made her eligible for molnupiravir. An immigrant from the Dominican Republic who came to Massachusetts 20 years ago, Reynoso said through a translator that she understood the medication didn’t have full FDA approval, but she trusted that her doctors and nurses would never give her anything that would harm her.
The health center had the pills delivered to her home, and her sore throat started improving within hours of taking them, she said. And she’s feeling much better now.