icon-folder.gif   Conference Reports for NATAP  
  HEP DART 2003: Frontiers in drug development for Viral Hepatitis
December 14-18, 2003
Kauai, Hawaii
Back grey_arrow_rt.gif
Combination Interferon Therapy: Infergen plus Actimmune
  Interim Results of a Pilot Study of the Combination of Type 1 (Infergen) and Type 2 (Actimmune) Interferons in Chronic HepatitisC Patients Who Have Failed to Respond to Peg-interferon Alpha 2 Plus Ribavirin
Reported by Jules Levin
C Leevy (New Jersey School of Dentistry and Medicine, Newark, NJ) and LM Blatt (Intermune Inc)
Treatment of chronic hepatitis C with pegylated IFN and ribavirin leads to a sustained virologic response in about 50% of patients. Response to therapy can be predicted early in the course of treatment (week 12) by assessment of serum HCV RNA concentrations. Patients who have not had at least a 2 log10 reduction in their viral load by week 12, have a 97%-100% chance of not responding to therapy and typically therapy is stopped. These patients have been termed “Null Responders” to pegylated interferon alpha 2 theapies. Preclinical studies have demonstrated strong synergistic antiviral and immunomodulatory effects of the combination of Infergen (IFN alfacon-1) and Actimmune (IFN-gamma 1b) in preclinical models of HCV. Given these data, we initiated a pilot study in 31 Null Responders to pegylated IFN alpha 2 + ribavirin.
31 patients were retreated with Infergen, 15 mcg SQ daily, and Actimmune 50 mcg SQ TIW for 48 weeks. All patients had previously received pegylated interferon and ribavirin for 12 weeks, and did not have at least a 2-log10 drop in HCV RNA (Null Responders) Serum HCV RNA was assessed at weeks 12, 24, 48, and 72 to determine viral kinetics and sustained virologic responses. Patients were monitored for constitutional symptoms and bloods were collected for serum chemistries and hematological evaluations.
At the end of 8 weeks of therapy, 32% of these Null-responder patients had undetectable HCV RNA (RT-PCR assessment), and a total of 65% of the patients had either a2 log10 or greater decline in viral load or were HCV RNA negative. Biochemical response was assessed by determination of serum ALT concentrations. All 31 patients had a reduction from baseline in serum ALT and by week 8, all patients had ALT values that were below the upper limit of normal. One patient discontinued therapy because of constitutional symptom complaints, all other patients tolerated the therapy well. There were 4 patients supported by growth factors for reductions in absolute neutrophil counts.
The authors concluded that retreatment of Null Responders to peginterferon plus ribavirin with Infergen+ Actimmune suggests preliminary promise by displaying tolerability and early virologic response and may be of benefit to patients; further srudy in a larger patient population is now being initiated.
Note from Jules Levin: I have heard a number of reports on the difficulty of tolerating high dose Infergen. Intermune has not yet displayed to me the conducting of well designed clinical trials using large enough numbers of patients and well controlled comparator arms of patients. This has made it difficult to interpret their data when studying Infergen at high dose for patients not responsive to peginterferon plus ribavirin. Study reports at conferences claim high dose Infergen was well tolerated but I hear conflicting reports from some doctors. I would like to see better conducted studies which better characterize safety, tolerability, and viral efficacy. Nonetheless, Infergen may provide efficacy for previous nonresponders to PegIFN+RBV but I think proper studies must be conducted by Intermune. There was information that Intermune was pegylated Infergen but I have not heard about this lately so I'm unsure if the company is moving ahead with this.