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RHEO Procedure Has Its Trials and Tribulations
Updated November 3, 2007
RHEO therapy has traveled a bumpy road. This is a running account of the developments.
Recent Background
On March 9, 2006, OccuLogix, Inc. provided an update of MIRA-1, the Company's phase III clinical trial using its RHEO System to treat the dry form of age-related macular degeneration ("Dry AMD").
On February 3, 2006, OccuLogix announced that a preliminary analysis of MIRA-1's intent-to-treat ("ITT") population had indicated that the study did not demonstrate a statistically significant difference in the mean change of Best Spectacle-Corrected Visual Acuity applying the Early Treatment Diabetic Retinopathy Scale ("ETDRS BCVA") between the treated and placebo groups at 12-months post-baseline. As expected, the treated group demonstrated a positive response. There was, however, an anomalous outcome of the control group.
The company then completed an in-depth analysis of the study data identifying subjects that were included in the ITT population but who deviated from the protocol, as well as those patients that had documented losses or gains in vision not related to retinal disease (e.g. cataracts, YAG capsulotomies, etc.). Those subjects in the ITT population who met the protocol requirements subsequently defined this modified per-protocol population.
In this analysis, eyes treated with the RHEO procedure demonstrated a mean vision gain of 0.8 lines of ETDRS BCVA at 12 months post-baseline compared to a mean vision loss of 0.1 lines of ETDRS BCVA in the eyes in the Placebo group. The result was statistically significant (repeated measure p value = 0.0147).
With respect to those in the MIRA-1 modified per-protocol population that had pre-treatment vision worse than 20/40, 50.0% of RHEO treated eyes improved after treatment to 20/40 or better and would be able to qualify for a drivers license 12 months post-baseline, compared to 20.0% of Placebo eyes.
MIRA-1 data support historical clinical and commercial experience with respect to the safety of the RHEO procedure, with observed treatment side-effects being generally mild, transient and self-limiting.
On June 8, 2006, OccuLogix met with the FDA to discuss the results of MIRA-1. At the meeting, the FDA advised that it would require an additional study of the RHEO System to be performed. Accordingly, the Company submitted its application in August 2006 for an Investigational Device Exemption ("IDE") with a new protocol.
On January 10, 2007, OccuLogix announced that the MIRA-1 trial "was a flawed study, in that 37% of the treated cases did not meet inclusion criteria, and at worst there was no evidence of effect." (PRELIMINARY ANALYSIS OF THE FINAL MULTICENTER INVESTIGATION OF RHEOPHERESIS FOR AGE RELATED MACULAR DEGENERATION (AMD) TRIAL (MIRA-1) RESULTS by Jose S. Pulido M.D. M.P.H., et al(Trans Am Ophthalmol Soc 2006;104:221-231).
Even though the number of serious adverse events was small, the study did not show an effect in the intent-to-treat group. The conclusion at that point was that "rheopheresis should not be performed for AMD outside of an approved randomized controlled trial."
In the group that completed at least one treatment, 27% of the enrollees dropped out of the study or had serious complications. In addition, all of the data from 37% of the treated patients and 29% of those that received placebo therapy had to be deleted due to flaws in the science. There was, therefore, insufficient data to show a treatment benefit.
Recent Developments
On January 29, 2007, OccuLogix announced that it had obtained Investigational Device Exemption clearance from the U.S. Food and Drug Administration ("FDA") to commence its phase III study.
On November 01, 2007, however, OccuLogix announced that, in light of the Company's current financial position, it had indefinitely suspended its RHEO System clinical development program. This decision followed a comprehensive review of the respective costs and development time-lines associated with the products in its portfolio.
To read more about the procedure and the early trials, see Clinical Trials Assess Rheopheresis on this site.
For further explanation of the terms used in this article, see
the MD Support Glossary and Eye Anatomy pages.