Reformulated Generic Could Accelerate COVID-19 Recovery

With investigators working to develop therapeutics for coronavirus disease 2019 (COVID-19) at a record pace, repurposing available drugs that can directly enter phase 3 trials may allow for rapid approvals.

Dapsone, a generic oral antibacterial, may offer one such opportunity. Generic dapsone is being investigated in a large phase 3 trial in Canada and the United States for its ability to mitigate severe pulmonary inflammation in patients with COVID-19, potentially reducing hospital admissions.

“While aggressive mitigation strategies are being implemented to slow the spread of [severe acute respiratory coronavirus 2 (SARS-CoV-2)], we must also concentrate our efforts on developing and implementing scientifically sound drug candidates using high-quality randomized controlled trials,” principal investigator Jean Bourbeau, MD, MSc, FRCPC, said in a statement from McGill University Health Centre, the sponsor of the trial. “Reformulating an existing drug has many advantages.”¹ Bourbeau is a senior researcher at the Research Institute of the McGill University Health Centre in Montreal, Canada.

Dapsone is an affordable and safe oral antibacterial with anti-inflammatory and immune-modulatory properties and has been used for decades against HIV, lupus, malaria, and many other inflammatory infections.¹

“The metabolic, pharmacokinetic, and toxicological properties of dapsone have been well documented, so we understand its mechanism of action, how it’s absorbed by the body, and how it might minimize the inflammatory process in the lungs and reduce COVID-19 complications that lead to hospital admissions, intubation, intensive care, and mortality,” Bourbeau said. “We also know its [adverse] effects, which could help us avoid prescribing it to at-risk patients.”¹

The DAP-CORONA COVID-19 study is a multicenter, parallel, placebo-controlled, randomized, triple-blind trial. The drug will be administered to symptomatic outpatient adults in the early stages of the disease, with the hope of minimizing the cytokine storm triggered by the virus.¹ Cytokines are proteins produced by the white blood cells that help coordinate the body’s immune response, Bourbeau explained. However, when the immune system overreacts, it releases excessive amounts of cytokines, leading to hyperinflammation.¹

Cytokine storm in patients with COVID-19 is a critical condition characterized by overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multiple-organ failure.² Cytokine storm has been noted in several viral infections, including influenza H5N1 and H1N1 viruses, as well as severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, both of which are closely related to SARS-CoV-2.²

Early recognition and treatment are essential.² Several agents targeting cytokines have been studied, including anakinra and tocilizumab, which has been approved by the FDA for a phase 3 clinical trial in hospitalized patients with severe COVID-19 pneumonia.² Depending on the upcoming trial results, dapsone may present a new option.

“Because of its anti-inflammatory, immunomodulatory, and immune-suppressive properties, dapsone works on the adherence of immune cells called neutrophils to prevent the release of cytokines,” Bourbeau said in the statement. “By administering the drug as soon as symptoms start, we hope to attenuate the lung inflammation that is the most frequent cause of worsening symptoms and complications requiring hospitalization.”¹

The trial was launched in September 2020, with more than 2000 symptomatic outpatient adults. Participants are 70 years and older, or they are younger with at least 1 high risk. The investigators are using a novel platform to screen, receive consent, and monitor patients remotely throughout the trial. Immunomodulatory agents, such as dapsone, could be a significant advancement in therapeutics for COVID-19, according to Bourbeau.¹

“With the need to prevent complications leading to hospital admissions and the absence of proven effective treatments for COVID-19 outpatients, showing that dapsone has a net clinical benefit should be a public health priority,” he said.¹

REFERENCES

• Old drug, new therapy: RI-MUHC-sponsored phase III clinical trial ready to test repurposed dapsone to tone down lung inflammation caused by COVID-19. News release. McGill University Health Centre. September 2, 2020. Accessed October 19, 2020. https://muhc.ca/news-and-patient-stories/ research/old-drug-new-therapy-ri-muhc-sponsored-phase-iii-clinical-trial
• Ragab D, Eldin HS, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol. 2020;11:1446. doi:10.3389/fimmu.2020.01446