Janssen Pharmaceuticals announced results from the Phase 2b Topaz Trial which demonstrated that treatment with pimodivir (JNJ-63623872) significantly decreased viral load over seven days versus placebo, in adult patients with acute, uncomplicated seasonal influenza A. Patients treated with pimodivir and oseltamivir (OST) also demonstrated a significantly lower viral load compared with those who received pimodivir alone at the same dose.

The primary endpoint data for the trial, presented in an oral presentation at the 5th International Society for Influenza and Respiratory Diseases Antiviral Group (ISIRV-AVG) Conference in Shanghai, China, showed treatment with pimodivir resulted in a statistically significant decrease in area under the curve (AUC) of viral load (by quantitative real-time-polymerase chain reaction [qRT-PCR]) over seven days from start of dosing, compared with placebo.

Differences in AUC are adjusted for baseline viral load and time from onset of influenza symptoms to the start of treatment (≤24 hours or >24 to 48 hours).

No significant safety concerns were noted with pimodivir treatment in the study. The most frequently reported treatment-emergent adverse events were diarrhea and nausea. Incidences of diarrhea (reported mostly as loose stool without increased frequency) were more common in individuals treated with pimodivir 600 mg (as mono- or combination therapy) than those treated with pimodivir 300 mg or placebo.

Pimodivir received U.S. FDA Fast Track designation in March 2017 due to its potential to address an unmet medical need in those who develop influenza A infection and who are hospitalized or at high risk of related complications. Phase 3 studies are anticipated to start in the second half of 2017.

“Influenza is one of the most serious global public health threats and important concerns remain about the emergence of antiviral resistance and the lack of approved medications for use in people hospitalized with the virus. Through the development of pimodivir, Janssen aims to provide a treatment option for people infected with the influenza A virus that will address these gaps,” said Julian A. Symons, D.Phil., Vice President, Disease Area R&D Leader, Respiratory Infections, Janssen. “The results of the Phase 2b study demonstrated that pimodivir, given either alone or with oseltamivir, significantly decreased the influenza viral load and therefore, if successfully developed and approved, could be an important treatment option for influenza A.”

Pimodivir, discovered by Vertex Pharmaceuticals*, is a first-in-class inhibitor of the PB2 subunit of the influenza A polymerase complex. By targeting an alternative part of the viral replication process, pimodivir may successfully treat influenza A virus infections that have developed resistance to existing antiviral drugs with other modes of action. The pimodivir development program receives funding support from the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, under contract HHSO100201500014C.

Influenza, which is commonly known as “the flu,” remains one of the most serious public health challenges. Worldwide there are more than one billion cases each year, resulting in approximately five million cases of severe illness and up to half a million deaths. In addition to the burden of seasonal influenza, the pandemics of the 20th and 21st centuries exemplify the threat the influenza virus presents; in 1918, the Spanish influenza pandemic alone caused approximately 50 million deaths worldwide. In an effort to combat antiviral resistance and address the global need for new and improved treatment options against influenza, Janssen is committed to exploring the development of multiple compounds with differing mechanisms of action.

*In 2014, Janssen entered into an exclusive license agreement with Vertex for the worldwide development, manufacturing and commercialization of pimodivir