PHILADELPHIA—Hemispherx Biopharma Inc. has reported the results of in-vitro studies of natural killer (NK) cells obtained from patients with chronic fatigue syndrome (CFS) together with a comprehensive review of relevant literature to assess the incidence of NK cell functional deficiencies in CFS. Their work has revealed that low NK cell cytotoxicity (NKCC) is consistently reported in patients with CFS compared to normal controls. Additionally, laboratory studies revealed that Hemispherx' Ampligen (rintatolimod), an experimental therapeutic, increased in-vitro NK activity in cells from CFS patient donors. NK cells are a type of cytotoxic lymphocyte, or white blood cell, that play a key part in the immune system in responding to infection and tumor formation.

 

CFS is characterized by “overwhelming fatigue and a host other symptoms that are not improved by bed rest and that can get worse after physical activity or mental exertion,” according to the U.S. Centers for Disease Control and Prevention (CDC). There are no known causes of CFS, nor diagnostic tests for the condition. The CDC defines CFS using the 1994 CFS case definition, which requires meeting three criteria: chronic fatigue for six or more consecutive months that isn't due to other medical conditions; fatigue that significantly interferes with daily life; and four or more of eight symptoms, which include post-exertion malaise, unrefreshing sleep, significant memory or concentration impairment, muscle pain, joint pain without swelling or redness, headaches of unusual severity or pattern, tender lymph nodes and/or a frequent or recurring sore throat.

 

In reviewing the medical literature available for CFS, 88 percent (15 of 17) published studies evaluating NKCC in patients with CFS concluded that the disease is associated with a reduction in NKCC compared to healthy controls. In addition, the published literature also presented data that support the theory that there is a connection between lower NKCC and a higher level of CFS symptom severity.

 

Ampligen was found to increase mean NK cell activity in-vitro more than 100 percent in the 15 CFS patients who donated NK cells. Mean age for the subject population was 48 years, and two-thirds of the donors were female. The increase in NK cell activity was achieved with concentrations of Ampligen achievable with a standard clinical treatment regimen of 400 mg twice weekly. More than 100,000 doses of the therapeutic candidate have been administered clinically, principally to CFS patients.

 

Hemispherx' clinical trials in CFS have traditionally emphasized quantitative measures of increased physical performance, such as a Phase 3 trial that compared twice-weekly IV Ampligen vs. placebo in 234 patients with long-term, debilitating CFS. The primary endpoint was intra-patient change from baseline at week 40 in exercise tolerance, and patients that received Ampligen in that time frame improved intra-patient placebo adjusted exercise tolerance 21.3 percent from baseline in an intent-to-treat analysis. (Correction for subjects with reduced dosing compliance increased placebo adjusted improvement to 28 percent.) The observed improvement represented roughly twice the minimum deemed medically significant by regulatory agencies.

Though the U.S. Food and Drug Administration (FDA) denied approval of a marketing application for Ampligen in December 2012, Hemispherx has remained in discussions with the FDA and other regulatory authorities to determine potential paths to advance Ampligen for the treatment of severe CFS. Ampligen falls into a new class of specifically configured RNA compounds targeted as potential treatments for diseases with immunologic defects and/or viral causation.