Ampligen FAQ

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Frequently Asked Questions about Ampligen

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.

To date, HEMISPHERx and its subsidiaries have received over 200 patents internationally to protect its proprietary position in NA and related drug technologies.

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 immunity.)

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 occurs.

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 Prevention (CDC).

Where is Ampligen available? As of this writing (December 1996), Ampligen is available to patients in Canada and Belgium under cost recovery programs.

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 program.

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:
December 10, 1996


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