[2] Although Ampligen was initially cleared for use in Canada in 1997,[3] and obtained orphan drug status for treatment of ME/CFS in the European Union in 2000, it is approved for use only in Argentina.

In 2007, Hemispherx filed a new drug application with the U.S. Food and Drug Administration (FDA) to market and sell rintatolimod for the treatment of CFS,[6] but this was rejected in December 2009, because the FDA concluded that the two randomized controlled trials "did not provide credible evidence of efficacy"[7][8] and "because of clinical, statistical, clinical pharmacology, nonclinical, product quality, and facilities inspection deficiencies.

However, there is a small amount of evidence from preliminary clinical studies of limited scope indicating that administration of rintatolimod may improve the daily quality of life of people diagnosed with CFS.

"No serious safety issues have resulted from the administration of about 75,000 doses IV (most commonly 400 mg) twice weekly for up to one year periods or greater.

"[14] A mild flushing reaction has occurred in about 15% of patients, and more rarely reported side effects include chills, fever, malaise, leukopenia, neutropenia, and leukocytosis.

They are part of a family of "pattern recognition" receptors that detect pathogens immediately, long before the slower adaptive immunity can intervene against foreign invaders.

The new compound, called Ampligen (for AMPLIfied GENetic activity) stimulated interferon production like poly I:C, but with much lower toxicity.

By the late 1980s, Carter and his company, HEM Research, Inc., were pursuing human therapeutic uses for rintatolimod, as well as nontherapeutic uses, such as diagnostic testing for HIV and protecting plants from pathogens.

It has also been available under Canada's Special Access Program for both CFS and HIV treatment since 1996, with marketing rights controlled by Biovail Corporation International.

[26] Bioclones (PTY) Ltd, a UK based company, was granted the exclusive marketing rights to rintatolimod in the United Kingdom, Ireland, and several countries in the Southern Hemisphere.

[28] Over its developmental history, rintatolimod has received various designations, including "orphan drug product" and "emergency compassionate cost recovery sales authorization", both from the FDA, and "promising" clinical outcome recognition based on the evaluation of certain summary clinical reports (AHRQ, Agency Health Research Quality).

"[30] In October 2007, Hemispherx BioPharma submitted their first new drug application (NDA) to the FDA for rintatolimod to treat CFS.

[31][32] The company received a Complete Response Letter from the agency on rintatolimod's NDA in December 2009, requesting further data.

The new study report, "Low Natural Killer (NK) Activity Observed Across the Chronic Fatigue Syndrome (CFS) Disease Spectrum," has been submitted as a scientific paper for peer review and publication.

[36] Clinical testing is currently under way to determine whether NK cell activity augmentation by rintatolimod in vivo associates with lessened CFS disease severity and increased physical endurance and performance measures.

[36] Although Ampligen was initially cleared for use in Canada in 1997,[3] and obtained orphan drug status for treatment of CFS in the European Union in 2000, it is approved for use only in Argentina.

[10] In 2007, Hemispherx filed a new drug application with the U.S. Food and Drug Administration (FDA) to market and sell rintatolimod for the treatment of CFS,[6] but this was rejected in December 2009, because the FDA concluded that the two randomized controlled trials "did not provide credible evidence of efficacy"[7][8] and "because of clinical, statistical, clinical pharmacology, nonclinical, product quality, and facilities inspection deficiencies.

[41] In 1998, Hemispherx Biopharma filed a complaint against Asensio and his company, alleging defamation, conspiracy, and interference with its business relations through a short-selling plot.

Efforts in 2015 to spur FDA approval of Ampligen include petitions, appeal for congressional hearing,[45] and popular social media group organizing.

[6][57] In December 2009, the FDA issued a complete response letter refusing Hemispherx's new drug application for rintatolimod's treatment of CFS.

Two toxicology studies had been completed as of 2007, which established the safety of intranasal and intramucosal methods of Ampligen administration as a vaccine immunostimulant.