What is Ampligen? Ampligen is a drug manufactured by HEMISPHERx Biopharma,
Inc. (NASDAQ:HEMX), Philadelphia, Pa. It is an antiviral and immune modulatory
drug under the nucleic acid class of drugs (NAs). Nucleic acid drugs are
designed to mimic the body's own digitalized informational molecules (called
DNA and RNA) which, in some laboratory and animal studies, reprogram certain
diseased cells to enhance their intrinsic disease capabilities.
Frequently Asked Questions about Ampligen
To date, HEMISPHERx and its subsidiaries have received over 200 patents
internationally to protect its proprietary position in NA and related
What is the generic name of Ampligen? Ampligen is the drug poly
I: poly C12U, which is a specific form of mismatched double-stranded ribonucleic
acid (dsRNA) where uridylic acid (U) substitutions in the polycytidylic
acid chain create periodic regions of non-hydrogen bonding in the helical
configuration. These changes, developed by HEMISPHERx, have resulted in
unique double-stranded RNA s, termed mismatched double-stranded RNA s.
Double-stranded RNA s act as modulators or molecules that mediate cellular
immune and antiviral activities.
How does Ampligen work? Ampligen inhibits viruses and tumor-cell
growth through pleiotropic, or multiple interrelated, mechanisms. Ampligen
up-regulates or down-regulates, as needed, two important enzyme systems;
(1) the 2 ,5 oligoadenylate synthetase/RNase L (2-5A synthetase/RNase
L) pathway; and (2) the P68 protein kinase pathway. Ampligen can induce
the production of 2-5A synthetase independent of interferon induction.
It also can activate both 2-5A and p68 protein kinase, while IFNs can
only induce production, but not activate, these enzymes, an important
biological distinction. Ampligen can also inhibit 2-phosphodiesterase,
an enzyme which destroys the product of 2-5A synthetase, biactive 2-5A.
These differences in mechanisms between IFNs and Ampligen result in clinical
and biological activities in interferon intolerant or resistant states
and synergistic interactions between Ampligen and interferon. (Once these
pathways are stimulated correctly, the cell responds with the production
of cytokines and lymphokines, the chemical messengers immune cells used
to communicate the memory response of antigen specific CD8+ cells, the
type of white blood cells thought to play the major role in cell-mediated
2-5A Synthetase/RNase L Pathway: Once 2-5A mRNA has been transcribed
by the genes in the nucleus (which earlier had been stimulated by messages
from the cAMP signal transition pathway), latent 2-5A synthetase is created.
Ampligen then activates this latent 2-5A synthetase and activated 2-5A
is created. Activated 2-5A, in turn, activates an enzyme called RNase-L,
which destroys viral RNA. (Oragen compounds directly stimulate the production
of active 2-5A.) 2-5A itself also can control the growth of certain human
tumor cells and inhibits reverse transcriptase, the enzyme both HIV and
HBV use for reproduction.
The RNase-L pathway is one of the immune system s standard response
to viral infection (termed intracellular immunity ). Some viruses, however,
such as HIV, herpes, and HBV overcome intracellular immunity by producing
substances that deactivate RNase-L, thereby releasing the virus to multiply
largely unchecked within the intracellular environment and clinical deterioration
Protein Kinase (p68) Pathway: The protein kinase (p68) pathway is also
affected in a similar manner. Once p68 kinase mRNA is transcribed from
DNA templates in the nucleus of the cell, p68 kinase is formed by translation
of the RNA message. Ampligen then induces the autophosphorylation of p68
kinase (essentially an activation of p68 kinase) that leads through two
other steps, elF2a and elf25-P to the inhibition of viral protein syntheses.
Who invented Ampligen? William A. Carter, M.D., the co-inventor
of Ampligen, was a pioneer in the clinical development of interferon,
a protein therapy now approved for more than a dozen viral diseases and
commanding a market in excess of $2 billion.
Where is Ampligen manufactured? Ampligen is currently manufactured
in the United States. To prepare a shipment of the drug, the Company receives
certain raw materials from Pharmacia/Upjohn functioning as a subcontractor
and then processes this material to develop the final finished drug using
HEMISPHERx facilities in Rockville, Maryland. Dosage units are then prepared
and tested for quality assurance.
Also, on December 18, 1995, Bioclones Proprietary (an affiliated company
of the South African Breweries Limited) as part of a strategic alliance
with HEMISPHERx, successfully completed the first production runs at a
larger nucleic acid manufacturing plant near Johannesburg, South Africa.
It is expected that the combined facilities of the partnership will,
with the passage of time, increase efficiency and thus lower the overall
manufacturing costs of this drug.
How much does Ampligen cost? The cost of manufacturing Ampligen
for the treatment programs in Belgium and Canada is relatively high (U.S.
$12-18,000) due to the low volume.
Who responds well to Ampligen? The results of Ampligen trials
in the United States and Belgium suggest that Ampligen may be an effective
treatment for a certain subset of Myalgic Encephalomyelitis (ME)/Chronic
Fatigue Syndrome (CFS) patients, namely those with severe debilitation.
The patients who entered the Ampligen trials met the strict case study
definition of ME/CFS established by the Center for Disease Control and
Where is Ampligen available? As of this writing (December 1996),
Ampligen is available to patients in Canada and Belgium under cost recovery
Belgium: A trial initiated in Belgium in May, 1996 by Kenny DeMeirleir,
M.D., Ph.D., from the University of Brussels, and by David Strayer, M.D.,
Professor of Medicine at Allegheny University, PA and Medical Director
for HEMISPHERx, was significantly expanded in November, 1996.
The expanded enrollment came at the request of the Belgian investigator,
who reported that after six months of Ampligen therapy, approximately
80% of the treated patients thereafter experienced an apparent complete
clinical recovery, which meant that the patient could go back to school
or to work. The typical patient had been bedridden because of CFIDS for
between 3 and 7 years prior to the initiation of the six-month treatment
The results of the Belgium clinical study were reported in San Francisco,
Calif., on October 14, 1996, at the scientific meeting of the American
Association for Chronic Fatigue Syndrome (AACFS). The improvements observed
in the two key measurements of physical performance used for the 24-week
long Belgium study confirmed and extended earlier findings obtained from
open-label and placebo-controlled American trials. The two measures of
physical performance were Karnofsky Performance Score (KPS), used to measure
activities of daily living; and exercise performance on a bicycle. KPS
improved 43% from a severely debilitating level of 53 to a level of 76.
A KPS score of 80 describes an individual who can perform normal activities
with effort, but continues to have limited signs of the illness. On the
bicycle testing, Belgium patients improved oxygen uptake significantly,
from 1.16 liters/minute before the twice-weekly Ampligen administration
of 200 to 400 mg, to 1.48 liters/minute after treatment.
In addition to physical improvement, significant cognitive improvements
were documented among patients on the three Ampligen trials, using the
cognitive subscale of the SCL 90-R or neuropsychological function tests.
The Ampligen treatments were generally well tolerated.
By contrast, spontaneous recovery of untreated patients suffering from
CFIDS is low. Earlier studies indicate that only 2% of the CFIDS population
report spontaneous improvement to normal function and activity levels.
Canada: On May 3, 1996 Canada's Health Protection Board made Ampligen
available to sufferers of Chronic Fatigue and Immune Dysfunction Syndrome
( CFIDS ), an extremely debilitating chronic viral condition with no previously
approved treatments in the U.S. and Canada.
On October 1, 1996, HEMISPHERx BioPharma, Inc. announced that it began
shipment of Ampligen to Rivex Pharma in Aurora, Ontario, a wholly-owned
subsidiary of Helix BioPharma Corp. Ampligen is administered in Canada
at the request of Canadian physicians.
Submitted by: email@example.com
December 10, 1996