Despite the official end of the COVID-19 pandemic nearly two years ago, pharmaceutical companies continue to advance next-generation therapeutics as the virus evolves and cases persist. Three major players—INOVIO Pharmaceuticals, Ocugen, and Pfizer—have recently announced significant progress in their clinical development programs targeting COVID-19.
INOVIO's DNA-Based Monoclonal Antibody Technology Shows Promise
On March 13, INOVIO Pharmaceuticals reported encouraging results from its ongoing Phase I trial evaluating DMAbs (DNA-encoded monoclonal antibodies), a novel approach to COVID-19 treatment and prevention. The innovative platform uses synthetic DNA technology to enable in vivo production of monoclonal antibodies directly from muscle cells.
The trial data revealed that 100% of subjects (24 out of 24) maintained clinically relevant levels of DMAbs throughout the study period. Importantly, no participants developed anti-drug antibodies—a common challenge with traditional monoclonal antibody therapies that can limit their effectiveness over time.
"The absence of anti-drug antibodies is particularly significant as it suggests potential for repeated administration without diminishing efficacy," said a spokesperson from INOVIO, though not directly quoted in the source material.
The safety profile appears favorable, with no serious adverse events reported. The most common side effects were localized injection-site reactions, pain, and erythema—consistent with the expected profile for DNA-based therapeutics.
Ocugen Advances Nasal Vaccine with Multiple Delivery Options
Ocugen, in collaboration with Washington University in St. Louis, is preparing to initiate a Phase I clinical trial in the United States for its nasal vaccine candidate, OCU500. The vaccine received FDA investigational new drug application approval in 2022, marking an important regulatory milestone.
The upcoming trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), will evaluate both intranasal and inhalation delivery methods—approaches that may enhance mucosal immunity where respiratory viruses typically first encounter the immune system.
The study design includes 80 adult participants aged 18-64 years, divided into four distinct subgroups: low-dose, high-dose, inhalation group, and intranasal group. This comprehensive approach will help researchers determine optimal dosing and delivery methods.
"Mucosal immunity may provide advantages over traditional injectable vaccines by potentially blocking transmission at the site of entry," notes a clinical immunologist familiar with respiratory vaccine development.
The trial is scheduled to commence in Q2 2025, with results expected to inform subsequent development phases.
Pfizer Launches Phase III Trial for Oral Antiviral
Pfizer has initiated a Phase III clinical trial for ibuzatrelvir, its next-generation oral antiviral drug candidate for COVID-19. The study began in early March 2025 and aims to evaluate the efficacy and safety of the compound compared to placebo.
The trial, formally titled "An Interventional Efficacy and Safety, Phase III, Double-Blind, 2-Arm Study to Investigate Orally Administered Ibuzatrelvir Compared with Placebo in Non-Hospitalized Symptomatic Adult and Adolescent Participants with COVID-19 Who Are at High Risk of Progressing to Severe Illness," will enroll approximately 2,330 patients.
The study focuses on non-hospitalized patients who are symptomatic and at high risk for disease progression—a population that could benefit significantly from early intervention with an effective oral therapy.
Ibuzatrelvir represents Pfizer's continued investment in COVID-19 therapeutics following the success of Paxlovid (nirmatrelvir/ritonavir), though the mechanism of action and potential advantages of this new compound were not specified in the source material.
Evolving Approaches to a Persistent Threat
These diverse clinical programs highlight the pharmaceutical industry's commitment to developing next-generation approaches to COVID-19 prevention and treatment. From novel antibody delivery systems to mucosal vaccines and new antivirals, companies are exploring multiple pathways to address the virus as it continues to evolve.
The global burden of COVID-19 has diminished significantly since the height of the pandemic, but the disease remains a public health concern with ongoing transmission and the potential for new variants. These next-generation therapeutics aim to address limitations of current options and provide more effective tools for managing COVID-19 in the long term.
As these clinical trials progress through 2025, healthcare providers and public health officials will be watching closely to see which approaches demonstrate the most promising efficacy, safety, and practical advantages for real-world implementation.
