A phase 2 trial has shown that interferon beta-1b (IFNB-1b)
(Betaferon/Betaseron, Bayer Healthcare)--a drug currently used to
treat multiple sclerosis (MS)--may be effective in chronic viral
cardiomyopathy (CVC). Dr Heinz Peter Schultheiss (Charité-Univ
Medizin, Berlin, Germany) presented the results at a late-breaking
trial session here today at the American Heart Association 2008
Scientific Sessions.

The study showed that IFNB-1b treatment led to a significant
reduction of viral load, with some evidence of clinical improvement
in those with CVC, and indicates for the first time that a biopsy-
based specific and causal therapy is possible for this condition,
Schultheiss noted. But he stressed that a phase 3 trial is needed
for definitive proof of concept and that he is currently in
discussions about this with Bayer. A final decision has not yet been
made on the phase 3 study, he told heartwire, but added that the
company "is much more positive than we thought."

Discussant of the study, Dr Michael Felker (Duke University, Durham,
NC), said that although this was only a phase 2 study, it is
nevertheless the largest randomized controlled trial conducted to
date in CVC. "Now, instead of just treating these patients with
heart-failure therapies," there may be the option of a specific
treatment, he said. However, he also stressed that a phase 3 trial
is needed to help understand the relative benefits and risks of IFNB-
1b in this patient population.

And Dr Clyde Yancy (Baylor University Medical Center, Dallas, TX)
told heartwire he has some concerns about this study: "This is
provocative but not definitive."

Differential Effect of IFNB-1b Depending on Causative Virus

Idiopathic, or unexplained, dilated cardiomyopathy (IDCM) is a
common cause of heart failure that disproportionately affects
younger patients and is the most frequent indication for heart
transplantation. Findings of viral persistence in the myocardium
have been found in around 50% of IDCM patients, leading to the
concept of a new clinical entity of CVC. Such patients have a poor
prognosis, Schultheiss noted.

In their placebo-controlled, randomized, double-blind, Europe-wide
multicenter study, 143 patients with CVC were randomized to one of
two doses of IFNB-1--4 MIU per injection or 8 MIU per injection--or
placebo every other day. This is a much lower dose than is used in
MS, Schultheiss said, "because we expected cardiovascular side
effects, but we didn't get them." Patients were treated for 24 weeks
followed by a 24-week follow-up phase and had to undergo serial
endomyocardial biopsies, as this is the only way to make a clear
diagnosis of CVC, the German doctor explained.

The primary end point was virus load reduction/elimination, which
was reduced overall in both groups taking IFNB-1b compared with
those on placebo (p=0.048). There was a significant effect of the
treatment on quality of life in the interferon group compared with
placebo (p=0.032), and there was also some indication of reduction
in NYHA class in those taking the interferon, he noted. However,
this lost significance by the end of the study due to an improvement
in this parameter in the control group.

There also appeared to be a differential effect of the therapy on
viral load reduction, depending on the type of virus causing the
CVC, Schultheiss noted, with the effect being greater in those with
CVC caused by enteroviruses or adenoviruses and less in those in
whom the CVC is caused by a parvovirus.

Many Hurdles, With Biopsies Perhaps the Biggest One

Discussant Felker told a press conference that the aim of this phase
2 trial "was not to prove definitively that something has a clinical
effect, but to look for a signal worth pursuing in phase 3."
Although this was a positive trial in many regards, there were a
variety of clinical events that did not reach significance with the
treatment, such as the six-minute walk, he noted.

And there remain many unanswered questions, he said, noting, "What
is the optimal timing in the disease course for interferon therapy?
Is interferon more effective against some viruses than others?

"IFNB-1b is an expensive therapy--around $10 000 a year, requiring
every-other-day injections," he pointed out. "A phase 3 trial will
help us better understand the benefits and risks."
Another important point, he stressed, is whether the low
complication rate of endomyocardial biopsy seen in expert centers in
this study can be replicated in broader clinical practice. "Although
biopsying the heart sounds barbaric, in the right hands it is safe,
but it's not something your average cardiologist is accustomed to
doing," he commented

One doctor on the press conference panel said the risks of
endomyocardial biopsy are similar to that of coronary procedures,
but Yancy told heartwire this is only true of patients who have
already had a heart transplant. In patients who have not had a
transplant--which was the patient population in this study--the risk
is higher, he explained.

"We need to pause for long enough to look for biomarkers so we can
forgo the issue of having to specify biopsy," Yancy said.

"I would have hesitancy moving ahead with this: it's costly, the
study has demonstrated only a reduction in viral load, and it's not
clear that this would improve clinical outcomes. The risks are
unrealized, and the patient cohort has not been defined in a precise
way," Yancy concluded.