Ampligen [polyI:polyC12U] is a
mismatched double-stranded RNA that acts by inducing
interferon production (
immunomodulator) and by activating an intracellular
enzyme (
RNase-L) against
viral RNA transcripts (
antiviral).
Ampligen, currently under development by Hemispherx Biopharma in the US, acts on the immunological system through T-lymphocyte stimulation and is indicated for the treatment of
chronic fatigue syndrome and acquired immunodeficiency deficiency syndrome (
AIDS), as part of the combined
therapy.
Ampligen is available for licensing worldwide. In February 2004, Fujisawa Deutschland GmbH, a subsidiary of Fujisawa
Pharmaceutical Co., entered into an option agreement with Hemispherx Biopharma with the intent of becoming a distributor for
Ampligen for the potential treatment of
chronic fatigue syndrome in Germany, Switzerland and Austria. An option fee of 400,000 euros was paid pursuant to the terms of the option agreement and upon execution of the Distribution Agreement, Fujisawa will pay Hemispherx fees and milestone payments with a potential worth of several millions of dollars. In September 2003, Hemispherx Biopharma Inc. entered into an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds,
Ampligen and Alferon N in the People's Republic of China. The agreement stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with
Ampligen for the treatment of HIV. All costs related to the trials are to be covered by GMC. Additionally, GMC has to develop and implement marketing and promotional programmes. In May 2003, Hemispherx Biopharma and the Center for Cell and Gene Therapy entered into a research project agreement that will see
Ampligen implemented in a protocol used in patients with relapsed EBV-positive
Hodgkin's Lymphoma. In March 2002, Esteve and Hemispherx Biopharma entered into a collaborative agreement under which Esteve will be the sole distributor of
Ampligen in Spain, Portugal and Andorra for the treatment of
chronic fatigue syndrome. Under this agreement, in addition to other terms, Esteve will also collaborate in the
drug product development by conducting clinical studies in Spain in patients coinfected with HIV/HCV. In July 2001 Hemispherx Biopharma announced that it had formed a strategic alliance with Empire Health Resources for clinical trials of
Ampligen in the treatment of HIV and hepatitis C virus
infections. Empire Health Resources, a healthcare management firm, will be responsible for accrual and retention of patients for HIV trials, and protocols for trials in patients with
hepatitis C or both HIV and
hepatitis C infections. Hemispherx has entered into a collaboration with RED Laboratories, and RED Laboratories NV expects that this will facilitate the continued development of
Ampligen. Hemispherx has also entered into an agreement with Schering Plough to use a Schering facility as its principal manufacturing platform in the US. This agreement may be expanded to include other territories. Hemispherx and AOP Orphan
Pharmaceuticals have signed a marketing agreement for
Ampligen for the treatment of
chronic fatigue syndrome for Austria, the Czech Republic, Poland and Hungary. In an arrangement between Hemispherx and Bioclones, Bioclones has certain marketing rights for
Ampligen in the Southern Hemisphere, UK and Ireland. In the US,
Ampligen has been granted orphan drug status for the treatment of
AIDS,
renal cell carcinoma (phase II, completed),
chronic fatigue syndrome (phase III) and invasive/metastatic
malignant melanoma (phase II). In August 2004, Hemispherx announced that it intends to use the proceeds from the private placement of company stock to complete the clinical work for its immunotherapeutics/
antivirals Ampligen and Oragens. Previously, Hemispherx submitted an application to the EMEA for the approval of
Ampligen for the treatment of
chronic fatigue syndrome; the first stage of th;) for the treatment of
chronic fatigue syndrome; the first stage of the regulatory review has been cleared. In 2000, Hemispherx Europe (Hemispherx) obtained orphan drug status for
Ampligen for the treatment of
chronic fatigue syndrome in the EU, providing Hemispherx with 10 years of marketing exclusivity following the launch of the
drug, as well as potential financial research benefits for the agent. In February 2000, Crystaal Corporation (now Biovail
Pharmaceuticals Canada) acquired exclusive marketing rights to
Ampligen in Canada, where it submitted an NDA for the agent for the treatment of
chronic fatigue syndrome. In the meantime,
Ampligen has been available since May 1996 under the Canadian Emergency Drug Release Programme for the treatment of
chronic fatigue syndrome and immune dysfunction syndrome by Rivex Pharma (Helix BioPharma). Bioclones has initiated clinical studies with
Ampligen for the treatment of
chronic fatigue syndrome in Australia. The active substance for
Ampligen is manufactured by F.H. Faulding Ltd. Clinical treatment programmes for
chronic fatigue syndrome in other Pacific Rim countries are planned.
Ampligen is available for severe
chronic fatigue syndrome on a named patient, cost-recovery basis in South Africa. Hemispherx has developed a 'ready-to-use' liquid formulation of the
drug and has begun treating patients with
chronic fatigue syndrome in ongoing clinical trials. Hemispherx has also developed an oral version of the
drug (
Oragen), which is undergoing preclinical evaluation. In February 2001, Hemispherx Biopharma announced that it was initiating phase II/III trials of
Ampligen in the treatment of late-stage, multidrug-resistant strains of HIV in the European Union. Patients treated in these studies will have exhausted all other treatment options. In July 2001, Hemispherx stated that
Ampligen was being evaluated in a phase IIb trial in patients with HIV in the US. The trial, comprising two studies, REARMI and REARMII (Research/Evaluation of
Ampligen for Retroviral Mutations I and II), will evaluate the ability of
Ampligen to prevent the emergence of mutated,
drug-resistant strains of the virus. 'Several hundred' patients currently on antiretroviral
therapy and at risk of viral relapse will be enrolled at centres in Connecticut, New York, Florida and California. A second phase IIb study evaluating the effect of
Ampligen on structured treatment interruptions (
STI) is also underway. Final results from this study were reported in December 2002. NIH sponsored studies of potential
therapies for SARS have identified
Ampligen as having unusually high and consistent
antiviral activity against human coronavirus, the pathogen implicated as the causative agent of the disease.
Ampligen demonstrated very high potency at very low concentrations (0.4 microg/mL) and had a favourable safety profile. In October 2003, Hemispherx announced that, based on these promising new results, the company will stockpile injectible and/or oral formats of
Ampligen and Alferon N. Independent researchers have demonstrated the
antiviral activity of
Ampligen against flaviviruses (West Nile virus,
Equine Encephalitis virus, Dengue
fever virus and Japanese Encephalitis virus) as well as virus classes associated with bioterrorism. In an animal study,
Ampligen was shown to prevent destruction of nerve cells, reduce virus concentrations in the brain and blood stream and increase survival rates. Researchers at the Rega Institute in Belgium have published results from an animal study demonstrating that
Ampligen was superior at protecting mice against coxsackie B3 virus-induced
myocarditis compared with pegylated
interferon. In May 2004 Hemispherx announced that it had filed an expanded US patent application covering the use of
Ampligen for the potential treatment and prevention of
severe acute respiratory syndrome (SARS) and dreaded emerging viruses.