Hemispherx's Ampligen Rehash Unlikely to Impress FDA
By Adam Feuerstein 09/27/12 - 07:00 AM EDT
PHILADELPHIA (TheStreet) --Three years after being rejected by U.S.
Food and Drug Administration, Hemispherx Biopharma (HEB) is back
seeking regulatory approval for Ampligen, its controversial therapy
for chronic fatigue syndrome.
Everyone loves a comeback story with a happy ending, but Hemispherx's
second attempt won't turn out any happier than the first. FDA is
likely to reject Ampligen again because Hemispherx ignored the
agency's demand to run a new clinical trial in chronic fatigue
Instead, Hemipsherx has spent the past three years doing essentially
nothing but re-analyzing data from the old Ampligen phase III trial
completed in 2004. FDA reviewed the original study already, deeming it
"lacking credible evidence of efficacy of Ampligen."
It would be highly unusual -- unprecedented, even -- for FDA to
reverse itself and find a retrospective rehash of old Ampligen data
more compelling this time around. FDA has been facing political
pressure to speed new drugs to market, particularly for diseases like
chronic fatigue syndrome with no current treatments. But this hardly
means FDA is going to throw out its drug-review rulebook.
FDA has scheduled an advisory panel for Dec. 20 to review Hemispherx's
Ampligen resubmission. The agency is expected to issue a final
approval decision on or before Feb. 2, 2013.
Ampligen's long odds haven't deterred speculators from bidding up
Hemispherx's stock price, just like they did in 2009. At Wednesday's
close of 90 cents, Hemispherx shares are up more than 220% since July
11 when the company announced plans to resubmit Ampligen for FDA
For those that don't remember, the phase III study enrolled 234
patients with chronic fatigue syndrome, randomized to treatment with
Ampligen or a placebo. The study's primary endpoint was improvement in
treadmill exercise tolerance at week 40.
Hemispherx announced positive results from the Ampligen study in May
2004, claiming that Ampligen patients demonstrated a 17.4% improvement
in treadmill exercise tolerance compared to a 4.3% improvement for
placebo patients -- a net difference of 13.1%. The result was
statistically significant with a p value of 0.047.
However, in May 2006, results from this same study were presented at a
medical meeting showing a 12.9% difference in treadmill exercise
performance between Ampligen and placebo that was not statistically
Depending on which data presentation you believe, the Ampligen study
was either a success or a failure. By rejecting Ampligen in 2009, FDA
clearly sided with the latter view.
In March, Hemispherx published the full data from the Ampligen trial
in the open-access science journal PLOS One. Once again, the study
results changed and got worse.
Ampligen-treated patients with chronic fatigue syndrome entered the
study with a mean, baseline treadmill exercise duration of 576
seconds. After 40 weeks of treatment, mean exercise duration rose to
672 seconds, or a 16.7% improvement.
The placebo patients began the study with a mean, baseline treadmill
exercise duration of 588 seconds and ended at 616 seconds, or an
improvement of 4.8%.
That works out to a placebo-adjusted improvement in exercise duration
for Ampligen of 11.9%. This benefit doesn't appear to be statistically
significant, however. The study, as published in PLOS One, makes no
mention of this intra-group comparison reaching statistical
The Ampligen study appears to have failed -- which gibes with the
FDA's decision to reject the drug and call for a new study to be
Hemispherx has not invested the money and time necessary to run a new
Ampligen study, choosing instead to change the way the primary
endpoint of treadmill exercise duration was measured. Instead of
comparing the two groups of Ampligen and placebo patients, Hemispherx
switched to analyzing the exercise data using each individual patient
as their own comparator.
On this "intra-patient" basis, Ampligen improved exercise duration by
36.5% compared to a 15.2% improvement for placebo patients. The net
difference of 21.3% was "statistically significant" with a p value of
0.047, according to the PLOS One study. Hemispherx CEO William Carter
and Medical Director David Strayer were lead authors of the study.
William Mitchell, a Hemispherx director, is also listed as a study
Hemispherx also conducted other, post-hoc analyses claiming to show
that patients who were able to exercise longer following Ampligen
therapy had improved quality of life and reduced dependency on
concomitant medications compared to Ampligen patients who couldn't
All of these new analyses of the Ampligen data were done
retrospectively, or long after the study was completed. Hemispherx has
made no effort to confirm any of these findings with new clinical
Following a meeting with FDA officials in June, Hemispherx claims the
agency agreed to review the new analyses of the Ampligen study in lieu
of data from a new clinical trial. However, Hemispherx also warned
that, "Whether these data provide adequate evidence of efficacy will
ultimately be a review issue, and there can be no assurance the FDA
will conclude the data are adequate to support approval of the
Investors would be wise to take that warning seriously.
A postscript: Omitted from this column is a retelling or discussion of
Hemispherx management's questionable actions and misleading statements
made during the previous Ampligen review cycle in 2009. I covered
Hemispherx extensively during this period, so feel free to go back and
read my prior stories:
Hemispherx's CFS Drug Is a Long Shot
Hemispherx Builds False Hope on Old Data
--Written by Adam Feuerstein in Boston.