Phase III study of Roche anti-inflammatory drug in Covid-19 fails

The company said that the COVACTA trial of Actemra in Covid-19 pneumonia had failed to meet its primary endpoint. Earlier this month, Regeneron and Sanofi announced that their study of a similar anti-inflammatory drug had also not met its primary endpoint.

Results of a trial of an anti-inflammatory drug from Swiss pharmaceutical giant Roche in patients with Covid-19 have shown the drug to be ineffective, the company said Wednesday, making it yet another repurposed drug that has failed to improve outcomes in the disease.

The drugmaker said that the Phase III randomized, double-blind and placebo-controlled COVACTA trial of Actemra (tocilizumab) in patients hospitalized with severe Covid-19 pneumonia failed to meet its primary endpoint of improvement on a seven-category ordinal scale over the course of 28 days. The study was supported by the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority.

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A Deep-dive Into Specialty Pharma

A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.

“People around the world are waiting for further effective treatment options for Covid-19, and we are disappointed that COVACTA did not demonstrate a benefit for patients in either clinical status or mortality at week four,” Roche chief medical officer Levi Garraway said in a statement. “We will continue to generate evidence to provide a more complete understanding of Actemra in Covid-19-associated pneumonia.”

Unlike direct-acting antiviral drugs such as Gilead Sciences’ remdesivir, Actemra is an IL-6-targeting monoclonal antibody used to bring down inflammation associated with autoimmune diseases. While unable to treat SARS-CoV-2 infection itself, it was hypothesized that the drug might be able to remedy the overactive immune system response associated with the most severe and fatal cases of Covid-19.

Nevertheless, the COVACTA study’s failure marks the second time in less than a month that a repurposed anti-inflammatory drug has failed to show any benefit in severely ill Covid-19 patients. At the beginning of July, Regeneron Pharmaceuticals and Sanofi said that their Phase III trial of Kevzara (sarilumab), also an anti-IL-6 drug, in patients requiring mechanical ventilation had failed to meet its primary endpoint. Regeneron is now focusing on development of a two-antibody antiviral cocktail against SARS-CoV-2, called REGN-COV2, Phase III development of which it also initiated earlier this month.

According to the COVACTA data, the difference between the treatment and placebo arms did not reach statistical significance, with a p value of 0.36 – far above the usual bar for statistical significance of 0.05 or less – and an odds ratio of 1.18 that ranged from 0.81 to 1.76. There was also no significant difference between the percentage of patients who died by week four. The time to hospital discharge was shorter for patients who received Actemra and had a p value of 0.037, but it cannot be considered statistically significant because the trial’s primary endpoint was not met.

Photo: Roche