Asahi's trial info regarding filtration efficacy.
Journal reference:
Fujiwara et al., “Double Fltration Plasmapheresis and Interferon Combination Therapy for Chronic Hepatitis C
Patients With Genotype 1 and High Viral Load,” Hepatology Research, 2007; 37:701–710
Redchip's description of that study:
There is a striking proof of concept for this novel approach to HCV therapy in the form of a clinical trial in which a Japanese company’s fi ltration system dramatically reduced viral burden and generated sustained viral responses (SVR)—the gold standard of effi cacy—in an unusually high percentage of patients, including those who had not responded to standard antiviral therapy or had relapsed after an initial response. Based
on these results, the company, Asahi Kasei Medical, is marketing the system for HCV treatment in Japan.
The most important clinical data on mechanical removal of HCV particles from the blood comes from a relatively large trial of Asahi Kasei Medical’s Plasmafl o and Cascadefl o fi lters, which are used to separate plasma from whole blood and to separate plasma components based on size, respectively. They are often
used together in what is called double fi ltration lasmapheresis (DFPP). A Japanese academic group compared the safety and effi cacy of interferon/ribavirin treatment alone to interferon/ribavirin plus DFPP.
Unlike previous studies, this trial tracked not only viral reduction but also sustained viral response. The study is described in a paper published in 2007.6
The multi-faceted trial enrolled 193 chronic HCV patients with high viral load (over 500,000 virus particles per milliliter of blood in two-thirds of patients) of the diffi cult-to-treat genotype 1b. Patients were divided into six treatment groups: 1) DFPP plus interferon for 24 weeks (n=5); 2) DFPP plus interferon and ribavirin for 24 weeks (n=10); 3) interferon and ribavirin alone for 24 weeks (n=59); 4) DFPP plus interferon for
48 weeks, with ribavirin in addition for the fi rst 24 weeks (n=15); 5) DFPP plus pegylated interferon and ribavirin for 48 weeks (n=30); and 6) pegylated interferon and ribavirin alone for 48 weeks (n=74). DFPP patients underwent as many as fi ve sessions lasting an average of three hours and 14 minutes. We consider Groups 5 and 6 the most relevant, as pegylated interferon and ribavirin for 48 weeks represents the current
gold standard of treatment.
DFPP plus drug therapy appeared to reduce viral load more than drug therapy alone both rapidly (24 hours after the start of treatment) and at later times at which virus was assayed (two weeks and four weeks after the start of treatment). As the fi rst chart below illustrates, the addition of DFPP generated a greater reduction in virus count in 24 hours than drug therapy alone was capable of in two weeks. Moreover, filtration appeared to have a similar effect in subsets of more diffi cult-to-treat patients, including those who had relapsed after initially successful treatment with drug therapy (second chart) and those who had not responded to a previous course of treatment with the drug combination (third chart). Although the comparisons are mostly not statistically signifi cant due to the small number of patients, the trend seems impressive.
(Cant paste the charts, but the Redchip report is available from me via e-mail or from Redchip)
Most strikingly, SVR was achieved in 70.8% of all patients who received drug therapy plus DFPP versus 50.0% in those who received drug therapy alone. This result was not statistically signifi cant (p=0.094) due to the small sample size but appears encouraging. Similarly, the addition of DFPP to standard
treatment generated better outcomes in relapsed patients (77.8% versus 50.0% SVP rate) and in previous non-responders (71.4% versus 28.6%). The higher SVP rates correlate well with the greater reduction in viral load.
The SVR rates achieved with the addition of DFPP are far above what is typically seen with standard care.
There are aspects of the study, however, that leave an element of uncertainty. First, although patients were randomly assigned to different combinations and durations of interferon therapy, they were allowed to choose whether to receive DFPP or not, with only 60 of 193 enrollees agreeing to the adjunct treatment.
As a result, the study cannot be considered truly randomized, the gold standard for clinical effi cacy trials. Second, almost all the endpoint comparisons, although always numerically in favor of DFPP, fell short of statistical signifi cance, meaning that there is a chance that the outcomes were the result of a fl uke. Largely, this resulted from the relatively small number of patients enrolled in the two most relevant cohorts—Groups 5 (n=30) and 6 (n=74), who received 48 weeks of pegylated interferon and ribavirin with or without DFPP,
respectively—and the number of patients in those groups who were not evaluated for effi cacy. Specifically, 36 of 193 patients were excluded from evaluation of SVR for reasons ranging from withdrawal of consent, failure to come to the facility for personal reasons, early termination of interferon therapy, and the continuation of therapy beyond the scheduled treatment. In Group 5 (standard of care + DFPP), 1 patient missed offi ce
visits, 1 stopped interferon therapy early, and 3 continued to receive interferon for longer than 48 weeks. Similarly, in Group 6 (48 weeks of standard of care alone), 16 patients were unevaluable for SVR—10 because of early cessation of interferon and 6 due to extended interferon.
Still, the response rates appear remarkable. Based on this study, Asahi Kasei Medical has been marketing the combination of Plasmafl o and Cascadefl o for HCV in Japan, where the devices were already approved for treatment of non-infectious diseases.
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