X-Message-Number: 18312 From: "Stephen Bogner" <> Subject: Re: Phase I Clinical Trials Reovirus Date: Mon, 7 Jan 2002 11:52:49 -0700 Just catching up on cryonet after holiday travel, and I would like to respond to Olaf Henny's post of 21 December. Olaf Henny writes... Can anybody please help me to make sense out of the interim results below? Specifically, I have no idea what to make of those figures relating to the plaque forming units, i.e. 10(7), 10(8) etc. ..... This is simply a short form of scientific notation i.e.. 1 X 10E7, 1 X 10E8. I found elements of the Oncolytics press release infuriatingly unspecific myself, but here is what I think the significance is: 1. These are interim results, reporting on 12 patients who have completed the protocol out of 18 patients enrolled. 6 patients are yet finish the protocol and are yet to be reported. 2. Previous reports have indicated that about 60% of cancers are RAS activated. However, these patients were not screened for RAS activation, since the purpose of the trial was to determine safety, and not efficacy. I am a bit troubled that they were not screened, since there was never an expectation that patients who did not have a RAS activated cancer would respond positively to the treatment. Basically, such patients were asked to participate in a trial that at best would do them no harm, but would not offer them any likelihood of benefit. Such as that may be, we know now that a) there were no adverse effects, and b) that there was no dose limiting toxicity observed. The obvious conclusion is that it will be safe to offer Reolysin to patients regardless of whether or not their cancer is RAS activated, although we would not expect non-RAS activated cancers to respond. (Significantly, a screening test has since been developed that will presumably allow for the determination of RAS activation prior to treatment.) So exactly what percentage of the 12 patients actually had RAS activated cancers? Unfortunately, this critical information - necessary to understand the significance of the efficacy results that are reported, such as they are - is not provided in this interim report. Also, it is known that RAS activated cancers occasionally transform into non-RAS cancers, and that the patient will then have both types of cancer simultaneously. The longer the cancer remains the more likely it is that it will undergo this transformation. So exactly what percentage of the patients had both types of cancer simultaneously, such that we would expect to see a partial response where RAS cancer would be destroyed but the non-RAS cancer would remain? After all, these were all very late stage cancer patients. Again, this critical information is not provided in the interim report. 3. Given that we do not know what percentage of patients had RAS activated cancers, how are we to understand the efficacy reports that are provided? In the press release we read the following: "As secondary endpoints, Oncolytics measured tumor response at both the treated lesion as well as remote metastatic sites. Evidence of viral activity in tumors was observed, which ranged from changes in tumor structure to partial and complete tumor regression in the injected tumors. 50% of injected tumors in the first four of six groups (twelve of the eighteen patients) demonstrated evidence of viral activity. Preliminary evidence of remote tumor responses were also noted in the first four groups." From this we can conclude that a) in at least one case there was complete tumor remission (i.e.. a "Cure", although technically you have to wait 5 years before you are allowed to say that, b)in other cases there was partial regression (How many cases? We don't know. How partial? We don't know. What changes in tumor structure? We don't know.), c) that there was the expected evidence of viral action against "remote" or metastatic cancers. Without knowing the breakdown between RAS-activated cancers and non-RAS activated cancers in the study we do not know if the REOLYSIN was in some degree effective against all of the RAS activated cancers (a 100% response rate) or only half of them (a 50% response rate). We do, however, know that it is safe - which is something that was known all along by the experts, but it is formal and official now. I have no idea why Oncolytics would choose to put out a press release that was missing the critical piece of information necessary to understand its significance. Apparently, a large number of shareholders are also annoyed about this, and the company has definitely heard about it. I do not think that they will make the same mistake in the future. Nevertheless, for what it is worth, there you are. Steve. --- Stephen Bogner, P.Eng. 403-544-4786 (v) Immersive Imaging Lab 403-544-4704 (f) Defense Research Establishment Suffield --- Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=18312