Tuesday, January 13, 2015

Ampligen improves Low Natural Killer (NK) Activity across the Chronic Fatigue Syndrome (CFS) disease spectrum

P HILADELPHIA, Jan. 12, 2015 (GLOBE NEWSWIRE) :: -- Hemispherx Biopharma, Inc. (NYSE MKT:HEB) (the "Company" or "Hemispherx"), reported today that it has conducted new "in vitro" studies of natural killer (NK) cells obtained from CFS patients in conjunction with a comprehensive review of the medical literature to determine the relative incidence of NK cell functional deficiencies in CFS disease. This review indicates that low NK cell cytotoxicity (NKCC) has been consistently reported in CFS patients compared to normal controls. In the new laboratory studies, Ampligen® (rintatoliod), an experimental therapeutic, was found to increase "in vitro" NK activity utilizing cells from CFS patient donors. The authors of the new report are all affiliated with Hemispherx.

NK cells are an important component of the innate immune response and may play an important role as a surveillance mechanism against viruses, other microbial pathogens, and tumor cells (Herberman", et al". Science 1981; 214:24-30). CFS is a debilitating disorder, characterized by disabling fatigue, flu-like symptoms, recurrent infections, and an apparent increased incidence of certain cancers, including lymphomas and brain tumors (Levine, "et al". Ann Epidemiol 1998;8:245-249). The vast majority (88%) of published studies (15 of 17) evaluating NKCC in patients meeting Centers for Disease Control (CDC) disease criteria for CFS concluded that CFS is associated with a reduction in NKCC compared to healthy controls. Two of the studies that did not find a difference in NKCC between CFS patients and normal controls appear to contain design flaws, which may have influenced results, for example, including the exclusion of CFS patients sick for 10 years or longer. Notably, studies at the University of Miami (176 CFS patients) found a range of 2 to 25 years from onset of CFS symptoms with an average of 10 years (Fletcher, "et al". PLoS One 2010; 5(5):e10817).

The medical literature indicates that the mean percent decrease in NKCC for the CFS population as defined using the CDC 1988 diagnostic criteria is significantly greater than that for the CFS patients defined by the CDC 1994 diagnostic criteria (the CDC 1988 criteria require more symptomatology to meet the requirements for a CFS diagnosis). Multiple published studies presented data, which support a relationship between a lower NKCC and a higher level of CFS symptom severity.

Ampligen® (rintatolimod), an experimental therapeutic, increased mean NK cell activity "in vitro" over 100% in the fifteen (15) CFS patients who donated NK cells. The mean age of the subject population was 48 years and two-thirds of the subjects were female. The observed NKCC increase was achieved with concentrations of Ampligen® achievable with a standard clinical treatment regimen of 400 mg given twice weekly. More than 100,000 doses have been given clinically, principally to CFS patients.

Historically, Hemispherx's double-blind, placebo-controlled and open-label clinical trials in CFS have emphasized quantitative measures of increased physical performance. For example, in a Phase III trial comparing twice weekly IV Ampligen® vs. placebo conducted in 234 subjects with long-standing debilitating CFS, the primary endpoint was intra-patient change from baseline at week 40 in exercise tolerance (ET). Subjects receiving Ampligen® for 40 weeks improved intra-patient placebo adjusted ET 21.3% from baseline in an intent-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo adjusted improvement to 28% (p=0.022) (Strayer, "et al". PLoS ONE 7(3):e31334. doi:10.1371/journal.pone.0031334).

The improvement observed represented approximately twice the minimum considered medically significant by regulatory agencies. An FDA Advisory Committee, convened in December 2012, when asked "Is the safety profile of Ampligen® adequate for approval for the treatment of CFS?", the "Yes" vote was 8, and the "No" vote was 5. When asked has the application "provided sufficient efficacy and safety data to support marketing of Ampligen® for the treatment of chronic fatigue syndrome?", the "Yes" vote was 5 and the "No" vote was 8. Thereafter, the Agency declined to approve the marketing application. Subsequently, the Company has been in dialogue with the Agency as well as selected regulatory authorities worldwide regarding potential paths forward to advance the experimental product for potential treatment of severe CFS. The evidence that severity of CFS is associated with progressive derangement of immune surveillance mediated by NK cells may afford a new path to identify opportunities for CFS therapeutic intervention. While NK studies were not systematically performed in the earlier well-controlled clinical study cited in the PLoS One peer-reviewed publication, improvements in vitality score, Activities of Daily Living score, and reduction in concomitant medications usage were observed. Quality-of-life improvements may be sequelae of improved immunosurveillance.

- See more at: http://globenewswire.com/news-release/2015/01/12/696686/10115028/en/Low-Natural-Killer-NK-Activity-Observed-Across-the-Chronic-Fatigue-Syndrome-CFS-Disease-Spectrum.html#sthash.6L3eBJ2q.dpuf

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