Comparison of Pegasys vs Peg-Intron for Treatment of Chronic Hepatitis C

By Liz Highleyman

A recent Argentine study published in the August 2006 Journal of Hepatology
http://www.hivandhepatitis.com/hep_c/news/2006/072506_a.html)
compared the pharmacokinetics, pharmacodynamics, and antiviral activity of
the two approved brands of pegylated interferon -- Pegasys (pegylated interferon
alfa-2a) and Peg-Intron (pegylated interferon alfa-2b) -- in 36 patients with
genotype 1 chronic hepatitis C.

The researchers found that patients receiving Peg-Intron had significantly
greater decreases in HCV viral load and a greater likelihood of achieving
a 2-log reduction in HCV RNA by week 8 (72% vs 44%; P = 0.09), even
though patients receiving Pegasys had higher plasma levels of the drug.
They therefore concluded that, “These findings suggest that the biological
activity, measured by early interferon-induced gene transcripts and early
antiviral responsiveness, may have been greater in patients treated with
[Peg-Intron], despite their lower exposure to the drug compared with patients
treated with [Pegasys].”

In an accompanying editorial in the same issue, however, hepatologists
Peter Jansen, MD, and Henk Reesink, MD, urged caution about reaching
premature conclusions as to which form of pegylated interferon is superior.

The authors noted that Pegasys is a more bulky branched molecule than
Peg-Intron; Pegasys has a molecular mass of 40 kilodaltons (kDa), compared
with 12 kDa for Peg-Intron. In general, they noted, Peg-Intron has a larger volume
of distribution and higher renal clearance than Pegasys. Typically, Peg-Intron is
dosed based on body weight, while Pegasys is administered as a flat dose.

Reviewing studies to date, they wrote that, “In terms of efficacy the books are still open. ”Many factors contribute to a treatment’s effectiveness, including drug-receptor interactions, maximum serum concentrations, trough levels, volume of distribution, and areas under the serum-concentration curve.

Jansen and Reesink noted that neutral head-to-head comparisons are the best way to determine the relative efficacy of different treatments, but such trials are expensive and difficult to conduct without industry sponsorship.

“To set up a study in a neutral environment, that is fair to both comparators, is difficult enough, to organize a fair study sponsored by companies, with shareholders looking over their shoulders, is doubly difficult,” they wrote. “Not only shareholders are looking on but also governments that ideally want to reimburse only one drug per indication. Therefore these studies have to be scrutinized to find out if science wins over economy.

”Small studies to date have provided conflicting results. The 36-person Argentine trial, sponsored by Shering-Plough (the manufacturer of Peg-Intron), found that 8-week treatment with weight-based Peg-Intron appeared to work better than fixed-dose Pegasys. Another small trial sponsored by Roche (the manufacturer of Pegasys), found that the drugs yielded similar response rates after 8 weeks of therapy. The Argentine study also found that Peg-Intron led to greater up-regulation of interferon-alfa response genes, but it remains unclear how the activity of these genes relates to sustained response to interferon therapy.

In the end, Jansen and Reesink emphasized, “it is the sustained viral response (SVR, the viral level 6 months after stopping the drug treatment) that really counts.” Response at 12 weeks is also useful, since patients who do not respond at this point can choose to stop treatment, thereby avoiding side effects and reducing cost. A larger study called IDEAL (also sponsored by Shering-Plough) is scheduled to report comparative SVR results in the first half of 2007.

“In view of the more than 175 million patients who are infected with HCV, the stakes for the industry are high,” the authors concluded. “We as hepatologists should not be too naïve in thinking that these comparison trials are designed and conducted by the industry for purely scientific reasons. For the industry these trials are, economically speaking, life or death. We should continue to make sense of the data and we should not decide too quickly that one drug is better than the other.

8/8/06

”Reference

P L M Jansen and H W Reesink. Antiviral effect of peginterferon alfa-2b and alfa-2a compared. Journal of Hepatology 45(2): 172-173. August 2006.