INFERGEN - New Hope For People With Hepatitis C Who Are Non-Responders To Prior Interferon Therapy
In 1986, three years before the hepatitis C virus was even identified, researchers already had established that alfa interferon was an effective therapy for some people with chronic hepatitis C (which was known prior to 1989 as non-A non-B hepatitis). In February 1991 Intron A (interferon alfa 2b) became FDA approved as the first treatment for chronic hepatitis C. Currently, three brands of alfa interferon—Intron A (interferon alfa-2b), Roferon (interferon alfa-2a), and Infergen (interferon alfacon-1 or consensus interferon)—are FDA-approved to treat people with chronic hepatitis C.
Therapy for chronic hepatitis C has advanced greatly since the discovery of the hepatitis C virus. Response rates to interferon treatment, which hovered around 10 percent in the early 1990’s, have increased to greater than 50 percent since pegylated interferon (both PegIntron and Pegasys) in combination with ribavirin (Rebetol and Copegys respectively) became the treatment of choice. However, there continues to be a large number of individuals who have either relapsed after initially responding to therapy (relapsers), or who have not responded to therapy at all (nonresponders). And this number is expected to triple over the next decade. In fact, it is estimated that the number of nonresponders will become larger than the number of people undergoing therapy for the first time.
Characteristics of nonresponders – often referred to as the “difficult to treat” group of individuals- are those with genotype 1 and a high viral load (HCVRNA > 850,000 IU/mL or > 2 million copies/mL). It is estimated that approximately 50% of all people in the United States with chronic hepatitis C fall into this category, and that approximately 70% of these people will fail to have a sustained response to therapy.
The likelihood of non-response to the standard course of pegylated interferon plus ribavirin can usually be predicted by the 12th week of therapy. If an undetectable viral load (HCV RNA < 50 IU/mL) or at least a 2 log decrease in viral load (for example a drop from 850,000 to 8500 IU/mL) has not been achieved by week 12 of therapy, sustained viral eradication is unlikely (0-3%). Treatment of nonresponders is a challenge for which limited options are available.
Goals of therapy are not only to suppress viral activity and replication, but also to decrease inflammation in and damage to the liver, to prevent future inflammation and liver damage, and to decrease a person’s chances of progressing to cirrhosis and liver cancer. Re-treatment with the same type of interferon is infrequently successful. Maintenance therapy may reduce the chances of progression to cirrhosis and its complications, but offers little or no hope of viral eradication. And, new therapies for HCV appear to be 5-10 years away from FDA approval. At present it appears that the most effective product for non-responders is Infergen.
In 1997, the first bioengineered (i.e. non-naturally occurring interferon) for the treatment of chronic hepatitis C was approved by the FDA. Initially manufactured by Amgen (who sold the rights to this product to the pharmaceutical company Intermune in June 2001) it is marketed under the name Infergen (also known as IFN alfacon-1 or consensus interferon). Infergen represents an effort to create a type of interferon that is superior to those produced naturally by the body. And, compared to other type-1 alfa interferons, Infergen has significantly greater antiviral activity (based on in vitro studies).
Infergen is currently the only FDA approved interferon with product label data expressly for patients who previously relapsed or who did not respond to other forms of interferon therapy. In fact, 58 percent of those who relapse after initially responding to treatment with alfa-interferon monotherapy experience a sustained viral eradication when retreated with 15 micrograms of Infergen three times a week for forty-eight weeks. And, 13 percent of those who do not respond to an initial course of alfa-interferon monotherapy experience sustained viral eradication when treated with 15 micrograms of Infergen three times a week for forty-eight weeks. And, between 40-44% of patients who do not respond to Rebetron (Intron A combined with ribavirin) experience a sustained viral eradication when treated with Infergen and ribavirin.
Studies are underway to assess the effectiveness of Infergen plus ribavirin for those who did not respond to pegylated interferon plus ribavirin combination therapy. One preliminary study (by Carroll Leevy, M.D. in New Jersey) found that 31 percent of people who failed to respond to previous pegylated interferon/ribavirin therapy achieved a nondetectable HCVRNA, and 69 percent experienced a 2-log drop of HCV RNA levels after 24 weeks of Infergen plus ribavirin combination therapy. The dose of Infergen used in this study was 15 micrograms given daily in combination with daily ribavirin for a period of 12 weeks; followed by 15 mcg Infergen given three times per week with daily ribavirin for a period of 36 weeks. An ongoing study (by S. Kaiser, M.D. and coworkers in Germany) is using high daily doses of Infergen - 27 mcg daily for the first 4 weeks followed by 18 mcg of Infergen combined with daily ribavirin for the next 8 weeks, then decreasing to 9 mcg Infergen daily in combination with daily ribavirin. The preliminary results from this study indicate that 56 percent of patients who did not respond to pegylated interferon plus ribavirin achieved nondetectable levels of HCVRNA after 24 weeks of Infergen plus ribavirin combination therapy. The preliminary results of these two studies are quite encouraging, and the final results are being eagerly awaited.
Trials of pegylated-Infergen (known as PEG-alfacon) plus ribavirin are currently underway. This combination is expected to be quite promising. Another promising therapy is that of Infergen combined with interferon gamma-1b (Actimmune). It has been found that when these interferons are combined, a synergistic antiviral effect results. Thus, HCV RNA levels decrease significantly -more than expected from simple the additive effect of the two drugs. In preliminary studies, after 12 weeks of Infergen 15 mcg daily in combination with Actimmune (50 mcg three times per week), 38% of people - all of whom previously were nonresponders to pegylated interferon plus ribavirin, achieved undetectable HCVRNA levels.
Nonresponders now have a solid basis for hope. The use of Infergen in those who have been nonresponsive to previous interferon therapy is a promising treatment strategy for this group of patients. The side effects of Infergen are similar to those of other interferons, and daily doses appear to be well tolerated by most patients. Deciding whether to re-treat is a difficult decision. Both the patient and the physician must weigh the pros versus the cons. When one factors in the potential consequences of cirrhosis and its complications, including liver cancer or liver transplantation, along with the statistics on re-treatment with Infergen, one senses the balance has tipped toward re-treatment.
All contents of this article are Copyright © Melissa Palmer, MD
Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).
Dr. Palmer is an internationally renowned hepatologist who has been practicing medicine since 1985. Prior to 2012, she maintained perhaps the largest medical practice devoted to liver disease in the United States. Dr. Palmer is Clinical Professor of Medicine at New York University Medical Center. Dr. Palmer graduated from Columbia University with a B.A. and was trained in hepatology (as well as medical school) at the Mount Sinai School of Medicine in New York City.
Dr. Palmer is Board Certified in Gastroenterology and in Internal Medicine.
She has authored numerous scientific publications in the field of hepatology in such peer-reviewed journals as Hepatology, Gastroenterology, Seminars of Liver Disease, Transplantation and Archives of Internal Medicine.
She is frequently called upon by the media for her opinion on various topics related to liver disease. Dr. Palmer has appeared many times on television as a liver disease expert and has been quoted in such publications as TIME magazine, Cosmopolitan magazine, Prevention magazine, the Los Angeles Times, and Newsday. She also has appeared in numerous videos and CD-Roms aimed at educating doctors and the public about hepatitis C and other liver diseases, such as primary biliary cirrhosis. Dr. Palmer lectures to the medical and general public on liver disease-related topics on a regular basis.
Dr. Palmer has performed numerous clinical trials on various experimental medications for the treatment of hepatitis.
Dr. Palmer is currently available for lecturing, investor and hedge-fund consultations, consultations to industry, and media interviews and appearances-- including television. For such matters, she can be contacted through hepatitismedia@gmail.com.
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