Pfizer sees 'mostly mild to moderate' safety profile in phase 3 COVID-19 vaccine study

Pfizer building
Pfizer expects early efficacy data for its COVID-19 vaccine in late October. (Tracy Staton)

As Pfizer moves ahead in COVID-19 vaccine research at record speeds, executives on Tuesday detailed a "mostly mild to moderate” safety profile, with rare instances of severe or grade 4 side effects.

In phase 3 data through Aug. 27, trial participants who'd received only the first dose experienced mostly fatigue and headache, with other cases of muscle pain, diarrhea, chills and joint pain reported, according to a presentation from an investor event (slides 23 and 24).

Pfizer is advancing the vaccine in partnership with BioNTech, which developed the mRNA program. The data remain blinded; only the independent data monitoring board knows how the side effect reports stack up between the placebo and vaccine groups. But the board would notify Pfizer if any safety concerns arose, the company's head of vaccine research Kathrin Jansen said Tuesday.

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The safety data disclosure comes after AstraZeneca, another drugmaker in phase 3 COVID-19 vaccine testing, had to pause its high-profile trial after a suspected case of transverse myelitis, according to reports.

The trial has resumed in some countries, but not the U.S., where NIH officials said they were "concerned" about the case. On Tuesday, NIAID director Anthony Fauci told CNN it was a "matter of time" until the trial starts back up.

In its presentation, Pfizer emphasized constant surveillance of safety reports from the trial. "Continuous monitoring is performed by Pfizer’s qualified personnel by reviewing individual and aggregate data on a blinded basis," the company said, and the monitoring board sifts through the unblinded data weekly.

That board "may recommend pausing or discontinuing [the] study at any time and has not done so to date," the presentation said.

Pfizer reported safety data for 5,664 people ages 18 to 64 and 1,816 people ages 65 to 85 who received one dose. In the younger group, 38% reported fatigue afterward, while 35% reported headache and 16% had chills. Eleven percent or fewer suffered joint pain, diarrhea or chills. The side effects percentages were lower among the older age group.

After the second dose, 36% of trial participants aged 18 to 64 reported fatigue, while 28% reported a headache and 18% reported muscle pain. Again, the data were blinded between placebo and the vaccine candidate. 

Most side effects after the second dose were mild to moderate, but some participants did experience severe or grade 4 side effects, according to the presentation. There were more severe side effects after the second dose as compared with the first dose, even though a smaller number of participants—1,682—were in that group. 

RELATED: Pfizer, BioNTech coronavirus vaccine candidate gins up antibodies in early trial 

In the wake of AstraZeneca's trial hold, COVID-19 vaccine safety has been front and center. Plus, political pressure has been a concern in the U.S., with President Donald Trump and others saying a vaccine could be available around the Nov. 3 election. In a new poll, a majority of Americans believe the FDA will approve a vaccine based on political pressure, not safety and efficacy.

On politics entering the scientific process, Pfizer CEO Albert Bourla said Tuesday it's "very disappointing." Pfizer entered a pledge with other vaccine developers to ensure that "no matter what others think," the company won't submit a vaccine for an emergency use authorization or approval without a conclusive data readout, Bourla said.

RELATED: Pfizer, AZ, Moderna and more pledge not to rush COVID-19 vaccines

This summer, Pfizer and BioNTech posted phase 1/2 data showing fevers and other side effects that were mostly brief and not severe. At a higher dose, one participant experienced severe injection site pain. The company didn’t proceed with that higher dose for the phase 3 trial. 

“We are pleased that this blinded tolerability profile show a mostly mild to moderate overall tolerability, consistent with phase 1,” Jansen said at Tuesday’s event. 

The company feels comfortable with the profile, Bourla said Tuesday, so it recently moved to increase its total trial enrollment to 44,000 and enroll more vulnerable patients. With the trial expansion, Pfizer seeks to learn how its vaccine might protect people with HIV or hepatitis B or C, execs said.  

About 29,000 participants in three countries are enrolled so far. Pfizer is planning further enrollment in Germany, Turkey and South Africa.

RELATED: Pfizer, Moderna's coronavirus shot rollouts could freeze up, experts say, citing cold-storage needs 

Meanwhile, amid the research effort, the drugmaker also set out to design a cold chain for distribution so that its vaccine can be properly stored—in extremely cold temperatures—until administered, Pfizer biopharmaceuticals president Angela Hwang explained. The company’s distribution centers are equipped with ultra-low temperature storage capabilities, and vaccines are shipped in thermal containers of between 200 and 1,000 vials, she said. Each container contains a GPS-enabled temperature monitoring device. 

At the point of use, whether a hospital, pharmacy or doctor's office, vaccines can be stored in ultra-low temperature freezers for six months, dry ice thermal containers for 15 days, or refrigerators for five days. Hwang expects the vaccines will be used quickly when they arrive to those destinations. 

Pfizer and BioNTech are the only partnership with end-to-end capabilities ranging from research to manufacturing to delivery, Hwang said. The partners are planning to deliver 100 million doses in 2020 and 1.3 billion in 2021.  

Looking forward, Pfizer is eyeing a potential “second-generation” vaccine for 2021 or beyond that could be given in one dose or would be stable at refrigerated temperatures, Jansen said.  

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