FDA Gives Inovio Green Light for Phase 3 Trial of DNA COVID-19 Vaccine

Inovio has received the FDA go-ahead for a phase 3 trial of INO-4800, a DNA plasmid vaccine against COVID-19.

The agency lifted a prior clinical hold on the study after Inovio satisfied questions about the vaccine and its needleless electroporation delivery system, Inovio’s Joseph Kim said on an investor webcast.

Inovio and partner Advaccine Biopharmaceuticals Suzhou Co. (China) will conduct the INNOVATE study in Mexico, Brazil, Columbia and Thailand, in addition to the U.S. The trial will evaluate INO-4800 in healthy adults aged 18 years and older, who will get two 2-mg doses given one month apart. The primary endpoint is virologically confirmed symptomatic COVID-19.

“We are aiming to have the interim phase 3 data available by the first half of 2022,” after which Inovio will apply for an Emergency Use Authorization, Kim said.

This is the first large-scale test of a DNA plasmid vaccine for COVID-19.  DNA vaccines have some unique advantages over mRNA vaccines, including a relative insensitivity to temperature. The vaccines have shown 1-year stability at temperatures of up to 98.6 degrees and have a projected 5-year shelf life at normal refrigeration temperatures.

The company’s proprietary delivery device is a key component of the vaccine system. The hand-held unit, powered by AA batteries, uses air pressure to force the vaccine into the epidermis. It then generates millisecond-duration electrical pulses that temporarily open pores in all cells lying within the electrical field, including immune cells. This allows the plasmid ring, encoded with the viral antigen, to enter easily. Electroporation increases the amount of DNA delivery by more than 1,000-fold compared to traditional injection delivery, the company said.

After uptake, immune cells use the plasmid DNA sequence to generate antigens; this stimulates an immediate immune response as well as the long-lasting humeral immune memory vaccines rely on. DNA vaccines do not interfere with or change in any way an individual’s own DNA, the company added.

“The CELLECTRA 3PSP device is designed specifically for a COVID-19 type pandemic scenario,” the company said in a press statement. The user-friendly design “allows for stockpiling of the device in quantity without maintenance … [It] has been designed with reliability, challenging environments, user needs and ease of large-scale manufacturing in mind.”

Development of this device really took off in 2019, with an $8.1 million investment from the medical arm of the U.S. Defense Threat Reduction Agency’s Medical Chemical, Biological, Radiological and Nuclear Defense Consortium.

The lifting of FDA’s clinical hold is another in a series of green lights flashing for Inovio, Kim said on the webcast.

“The World Health Organization shared on Oct. 26 that our candidate is one of two that will be trialed internationally in the Solidarity Vaccines study. We believe INO-4800 is well-positioned to combat this global pandemic.” — Michele G. Sullivan