Novartis has withdrawn its MAA for Joulferon® (albinterferon alfa-2b) for the treatment of chronic hepatitis C. The decision was based on preliminary feedback from European regulatory authorities indicating that new data would be requested.
Novartis believes that this additional information would not be generated within the time frame allowed in the European centralized procedure. Concerns included whether the therapeutic benefit offered by Joulferon, dosed once every two weeks, would be sufficient relative to risk, according to the companies.
The drug was developed by Human Genome Sciences (HGS) and Novartis under an exclusive, worldwide agreement established in 2006. The firms share U.S. rights, where the drug is called Zalbin, while Novartis is responsible for the drug in the rest of the world where it is called Joulferon.
The MAA submission was based on the results of two Phase III trials. ACHIEVE 1 was conducted in patients infected with genotype 1 virus, and ACHIEVE 2/3 was conducted in patients with genotypes 2 or 3 virus. The two studies treated a total of 2,255 patients.
The rates of serious and/or severe adverse events were comparable between the treatment and the control arms in each study, according to the companies. These events included severe and/or serious pulmonary infections and severe and/or serious respiratory, thoracic, or mediastinal disorders. Adverse events observed were those typically associated with interferon therapy, the companies add.
The trials did meet their primary endpoints, showing that 900 mcg Joulferon dosed every two weeks was noninferior to peginterferon alfa-2a dosed once each week in combination with ribavirin in interferon-naïve patients, HGS and Novartis report. In both studies half the injections of albinterferon alfa-2b achieved sustained virologic response comparable to that achieved by peginterferon alfa-2a, they add.
The drug is currently under review by the FDA; HGS submitted the BLA for Zalbin dosed every two weeks in November 2009, which triggered a $75 million milestone from Novartis. HGS and Novartis are also developing Zalbin dosed every four weeks, with interim results from a Phase IIb study in this regimen showing positive results.
Zalbin/Joulferon is a genetic fusion of human albumin and interferon alfa created using HGS’ technology. Human albumin is the most prevalent naturally occurring blood protein in the circulatory system, persisting in circulation in the body for approximately 19 days. Research has shown that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the therapeutic proteins, the companies point out.