hepdart paper - data analysis, page-15

Too Good to be True?

Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, has doubts about PSI-7977. "If you use it with ribavirin and no interferon, you get a 100% SVR; if you use it alone, you get a 100% SVR."

Dr. Bernstein accepts the efficacy of PSI-7977 for the moment, but is concerned that ELECTRON isn't powered to say much about the tolerability or resistance profiles of the drug.

"What we've found with most of these [polymerase inhibitors] is that if you use them by themselves, you get resistance; if you don't, they can be very difficult to tolerate," said Dr. Bernstein. "There was a drug being investigated at Mount Sinai — a polymerase inhibitor, NM286 — and those patients got severe diarrhea and could not tolerate it. According to the ELECTRON study, everything was perfect — no gastrointestinal issues, no apparent adverse events of any kind, and it worked 100% of the time without interferon, or ribavirin.... If it's true, it will be great. The holy grail is to try to rid HCV treatment regimens of interferon."

Although sincerely impressed, Dr. Bernstein, who has seen many drugs come and go, suspects that as larger phase 3 trials of PSI-7977 are conducted, polymerase-associated adverse events, tolerability issues, and treatment resistance patterns will emerge.