The take-at-home prescription pill from Pfizer expected to expand the arsenal of COVID-19 treatments later this month has a local backstory.
The first patient enrolled in the Phase 1B trial of the intravenous precursor to the drug, more than a year ago, arrived at El Camino Hospital in Mountain View with an active case of COVID and agreed to participate. From there, the trial grew through months and phases at El Camino and other sites around the U.S., and Pfizer successfully tested oral as well as intravenous variations of the antiviral.
The Food and Drug Administration approval handed down Dec. 22 for Paxlovid was the first given to an oral antiviral COVID treatment since the pandemic began. As of right now, severely limited supply means most healthcare providers have little or no access to Paxlovid doses. Patients at El Camino can’t get the pill – yet –
but production and shipping is ramping up over the next few weeks. Dr. Ganesh Krishna, the principal investigator who led the trial, said the hospital expects to receive doses “any time this month.”
The drug El Camino tested inhibits an enzyme, SARS 3CL protease, that the virus SARS-CoV-2 needs to be able to replicate. By preventing the virus from replicating, the medication shortened recovery time and stopped infections from progressing to more serious disease and death. Because the enzyme blocker affects viral replication, the drug must be used early in the course of the COVID infection, before the virus has prolifically replicated and the disease progressed to a full-blown inflammatory response.
The new pill, like other COVID treatments currently in use, is designed to prevent illness from becoming serious or life-threatening in higher-risk patients. It’s not going to be a routine option for all positive cases, the way Tamiflu has come to be deployed against influenza.
Pfizer began seeking Phase 1B trial participants with El Camino Health shortly after the pandemic began to shut down the country two years ago. John Tejeda, senior director of clinical research at El Camino Health, said enrollment began quickly during an urgent nationwide search for therapeutic solutions as the pandemic deepened.
At El Camino Hospital, Krishna and his team of investigators first assessed what dosing worked best for the infusion, and then how powerful the treatment’s effect proved to be. They needed to determine whether it halted disease progression in the mild-to-moderate patients who might otherwise be bound for an intensive care unit within weeks.
Facing a “desperate” clinical situation in the early days of the pandemic, with mounting global mortality and nonexistent vaccine options, Krishna said they were fortunate to admit a patient to El Camino Hospital who was willing to be the first trial instance of the infusion. Other treatment options explored during that era were either nonworking (hydroxychloroquine), in short supply (monoclonal antibodies) or lacking in robust data (Remdesivir), Krishna said. Participants who joined the placebo-controlled study at El Camino knew it offered at least a chance at inhibiting the virus from spreading in their cells.
In the early stages of a COVID infection, the virus invades the body and replicates itself, causing respiratory virus symptoms. Later stages of the disease, for patients in whom it progresses, are characterized by a hyperactive immune system triggering a “profound inflammatory response in the body, creating havoc in the patient’s multiple organ symptoms,” Krishna explained.
Once the host immune response has begun, the medication they were studying can’t do its work – viral replication has already happened throughout the body. Just as with Tamiflu’s inhibition of influenza, this new treatment must be given early to arrest the course of the disease.
Both Tejeda and Krishna said anyone experiencing symptoms in the setting of a positive
COVID test should check in with their doctor for assessment. The decision on when to hospitalize an early-stage patient, and/or pursue treatments like this new pill, depends on risk factors and symptom progression. The medical community wants to identify patients for whom very early drug administration can radically change the course of the disease.
“These days, often the patients will get an infusion of the monoclonal antibody therapy and we send them home and they have better outcomes,” Krishna said of already-available treatments with a timeline of efficacy similar to the new pill. “Given the spectrum of medications that are available to treat COVID, especially early on during the clinical course, if you have a positive test and have symptoms, you should discuss with a doctor.”
Tejeda noted that this capacity – to treat patients on an outpatient basis, with the new Pfizer pill and other available treatments – has been a thrilling progression for El Camino’s research group, which over the past year have watched their patients go from having no known therapeutic solutions to a multi-day hospital infusion to, now, the prospect of a five-day course of prescription pills taken at home.
Both Tejeda and Krishna spoke to the staffing crisis being driven by the current COVID surge, which is impacting local patients of all kinds who need health care – and pointed out that seeking health care proactively for a symptomatic infection is appropriate. Slowing down the surge via careful masking, social distancing, and isolating when symptoms of a virus emerge can help overburdened medical systems. But seeking care also can help, by potentially reducing the severity of disease and reducing the total amount of care needed.
“You won’t know what’s going on until you really evaluate (a patient) – what they think might be minor symptoms might be a sign of something serious, particularly if they have underlying health issues,” Tejeda said.
Most vaccinated people who don’t have underlying health issues won’t be a candidate for the pill even after it is readily locally available, unless they present with significant symptoms.
“If you have both vaccines and the booster, chances are that the manifestation of the disease is very mild and you’ll just get over it, if you even know (you’ve contracted it),” Tejeda said.
Despite the excitement they shared about the new treatment, both Krishna and Tejeda pointed to everyday behaviors as the most powerful protection against what the virus might hold for us in the near future.
“We are still learning about this disease process; science is advancing every day, our understanding of the disease entity and process is changing every day, and the virus is changing, too – we have more variants and it is difficult to project what is going to happen in the future,” Krishna said. “It is not time to let our guard down. The role of time-tested measures such as wearing a mask and social distancing can’t be over emphasized.”