THE SEQUENCE OF EVENTS--------------------------
STEP 1
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October 2001
The due diligence of Oxo Chemie AG is ongoing and on track to be completed within this fiscal quarter, with Oxo completing its
data collection of the Phase III study with WF10 in late stage AIDS. OXO expects to have the final results announced within
this quarter as well.
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November 2001
The due diligence of Oxo Chemie AG is almost completed, and we expect Oxo to have the final results of the Phase III study with WF10 in late stage AIDS announced as soon as the data is compiled.
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December 2001
Once all of these steps are completed, and actual ownership is transferred, we will be able to issue a press release announcing all of the details. In the interim, however, the critical day-to-day business of Oxo will be able to continue, and most importantly, with the help of Dimethaid's clinical and regulatory affairs departments, the pivotal Phase III study of WF10 in late-stage AIDS patients can now be completed, and the results announced when available.
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February 2002
In closing, I would remind our shareholders of Health Canada's refusal in 1992, to allow us to conduct any clinical trials in Canada with WF10, the immune-modulating drug developed by Oxo Chemie AG with which we are allied. As a result, Dimethaid suffered the embarrassment as a Canadian company of having to stand by and observe the clinical development of WF10 by Oxo Chemie in the US and elsewhere around the world, funded with the ever-weakening Canadian dollar. Despite Health Canada's shortsightedness, research on WF10 proceeded with Canadian investment dollars being spent outside the country in studies supporting the creation and continuation of scientific expertise elsewhere. As a Canadian I am embarrassed. As your CEO, I am unwaveringly committed to see the development of both PENNSAID® and WF10 to commercialization.
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August 2002
With the acquisition of Oxo Chemie, we now have full ownership of a second platform technology with potential applications in a variety of diseases characterized by immune dysfunction. A Phase III AIDS study with WF10 has been completed and we are down to the final days of verifying the data, after which we can complete the analysis.
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STEP 2 - Dr. Kuhne and Klaus Lindeiner are dismissed from Oxo Chemie. They are replaced by R. Keeler and Y. Schnarrenberger, who now govern Oxo Chemie.
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As reported in a Fribourg newspaper, 17 February 2004:
"Oxo Chemie AG, with F R I bour G, development, manufacture and trade of pharmaceutical products, etc. (FOSC of the 19.01.2001, p. 0438). Kühne Friedrich-Wilhelm is not a any more president; Lehmann Michael, and von Lindeiner Klaus, are not any more administrators; their signature is erased. Keeler Rebecca, registered administrator, are named president, and have the individual signature now. Schnarrenberger Yvo, registered administrator, are named secretary, with individual signature. New reviser: Associated AUDEXO SA, In Freiburg. Newspaper No 801 of the 17.02.2004 (02135994/CH-217.0.135.484-1 "
(NB: I'm indebted to Beckysboss for this outstanding piece of research. Thank you.)
stockhouse.ca
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STEP 3 - Dimethaid confirms Dimethaid's analysis..
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"A contract research organization, hired by Oxo to conduct the trial and collect patient information, transferred final data and case report forms to Dimethaid between March and May 2004."
"Pharmaceutical developer Dimethaid Research Inc. (TSX: DMX) has completed initial analysis of data from a Phase III study showing that immune regulating drug WF10 failed to meet primary endpoints>. An independent statistician, appointed by Oxo Chemie AG, has confirmed Dimethaid's analysis.."
Since R Keeler and Y Schnarrenberger now have absolute control at Oxo Chemie, with no voice for Dr. Kuhne - this means that Dimethaid governed confirmation of Dimethaid's analysis - with no opposition.
STEP 4 The departure of Judith Burgess.
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STEP 5 - "The truth, the whole truth, and nothing but the truth..."
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"The study, conducted in 229 late-stage HIV/AIDS patients at 32 sites across the U.S. and Canada, indicated no statistical difference between WF10 and placebo in affecting the time to onset of clinical progression, defined as any new AIDS-defining event or death. "
The WF10 Protocol:
"Criteria for Evaluation:
This study will evaluate the effects of WF10 on clinical progression, defined as any new occurrence of an AIDS-defining event or death; number, duration, and cause of hospitalizations; quality of life; and density of CD38 antigen on CD8+ T cells. The safety and tolerance of WF10 will be evaluated by analysis of adverse events and standard clinical laboratory tests.
Statistical Methods:
Demographic and background information will be summarized and presented as means, standard deviations, medians, and ranges for continuous variables and as counts and percentages for categorical variables. In general, all demographic and analytic data will be summarized using traditional statistical methods. The frequency distribution of the age data will be presented. Categorical data will be summarized using frequency tables. Confidence intervals will be calculated using standard formulae. All demographic and analytical between-group differences will be analyzed parametrically and nonparametrically.
Patient randomization to each of the two treatment groups (WF10 and Control) will be stratified by investigator. As a result, the Investigator will be included as a factor in each of the analyses performed. Where appropriate, treatment by investigator interaction will be tested. If the interaction should prove to be statistically significant, results may be summarized by treatment group within each investigator. If interaction is not found, investigators will be treated as blocking factors in the analyses.
All patients who receive at least one-half of the total intended dose will be included in all evaluations of clinical effect. All patients who receive any drug will be included in safety analyses.
An overall p-value of 0.05 or less will be considered to be statistically significant. The p-values of all tests will be reported without any correction for the multiplicity of tests performed. An intent-to-treat approach will be followed in all data summaries, using all available data in the analyses. Consequently, no adjustments to the data are intended for dealing with missing values or patients who withdraw prior to completing the study. A final statistical plan will be developed before locking the CRF database and opening the randomization for the final analysis at the conclusion of the study."
STEP 6 - "The questions..."
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1 - Intent to Treat - Each dropout is a failure. How many dropouts were there? Did dropouts create the statistical outcome?
2 - Why is the Primary Endpoint defined by Dimethaid as "time to onset of clinical progression", when it is defined by Oxo Chemie as "the effects of WF10 on clinical progression, defined as any new occurrence of an AIDS-defining event or death"?
3 - When did "time to clinical progression" become the primary endpoint? What about the other evaluation criteria? The alleviation of suffering, the absence of toxicity, quality of life, decrease in hospitalizations?
4 - What is the significance of Judith Burgess' departure in this context?
The sequence of events, and the narrowly-defined outcome here is highly questionable, IMO. Nobody expected WF10 to achieve miracles, but there was good reason to expect the emergence of two patient populations. The so-called failure is a self-affirming result obtained by Dimethaid, with little transparency. Many troubling questions surround this matter.
Jim |
