Some questions to IR and response...not really anything new, but I thought you might be interested.
Peter indicated that it was all right to post these.
Mr Block...
Thank you for the fax that you provided. I tried to contact you, however, it's not surprising that you would be busy. I do have some questions/comments/concerns:
1. Regarding study #107-96: Other than the fact that this study showed that Pennsaid produced a statistically significant difference between control and placebo, I am unable to come to much in the way of conclusions. The patient numbers are small (n=169), no methodology is provided, and the study compares Pennsaid to placebo. This study also appears to be an "in-house" study.
2. Regarding the studies published in "Pharmaceutical Research": Although I have not had the chance to review these studies as of yet, they appear to be toxicological or pharmacokinetic type studies.
Q: Has study #107-96 been published in a peer reviewed journal?
Q: In your submission to the various regulatory agencies, do you have any comparative studies against any other NSAID agent?
Q: Can you elaborate on this "phase IV" study that is supposed to accrue some 3000+ patients?
Having been on the Silicon Investor, obviously many of the participants are becoming anxious and impatient. This is of course, understandable. The wheels of bureaucracy turn slowly,
I DO, however, have a major concern in that, from what I've been able to find out so far, the data that you have available to support the use of Pennsaid is not particularly persuasive (from a clinical standpoint).
Thanks for your time.
Jeff Chan
Response
Dear Mr. Chan,
Thank you for your interest in Dimethaid Research. Let me deal with the issues you raised, trying to keep to your order of questions.
Study #107-96 was conducted at a number of sites across Southern Ontario. The measurement of pain relief (primary variable) reduction of stiffness (secondary variable) and increased flexibility (secondary variable) were all done using the WOMAC methodology. Measuring something as subjective as pain is very difficult. WOMAC was specifically developed as a measurement of the variables we studied for osteoarthritis in either the knee or hip. Our study was done on the knee.
WOMAC is an internationally recognized methodology for osteoarthritis trials and is accepted by the agencies.
The design of the trial was discussed, in advance, with the regulatory agencies. While approval of the design is not something that would ever be forthcoming, these discussions are nonetheless extremely useful in determining if our results will ultimately be accepted by the agencies. We are confident this will be the case for PENNSAID(r) Lotion.
The three arms of the study were established to measure the benefit of our drug (carrier + active) versus just the carrier (control) versus a placebo. The intent was to prove statistical significance of our drug and to measure whether our carrier had any measurable efficacy on its own. The analysis, conducted for us by the Robarts Institute in London, concluded that only PENNSAID provided statistically significant benefits in either the primary or secondary variables. There was no statistical significance in the efficacy between control and placebo.
While the patient numbers may appear to be small, statistical significance for efficacy cannot be discounted for this reason. In fact, you could argue that a small sample size can present a huge obstacle to a Company as any one patient that does not show benefit with the drug can skew the results quite significantly. Where the size of the study may be of greater significance is safety and that is where our open label trial has been of great benefit.
In March 1995 we were granted permission by Health Canada to conduct an open label safety study with PENNSAID(r) Lotion. This allowed us to enroll any physician in Canada as an investigator in the study. These investigators in turn would "enroll" patients -- in other words, they could prescribe the drug to their patients. This is known as an open label study which means that both the patient and physician are aware they are dealing with the drug (as opposed to double-blind trials in which no one knows if they are receiving the drug or placebo). Since that time, we have enrolled over 1100 physicians who have in turn prescribed PENNSAID to over 3300 patients. This study is a safety study and cannot measure efficacy. We have not had a single serious adverse event affecting either the gastro intestinal tract or kidneys reported throughout the study. Serious adverse events affecting the GI tract and kidneys are some of the most common and fatal side effects associated with administration of oral non-steroidal anti-inflammatory drugs (NSAIDs). In fact, the Canadian Arthritis Society estimates that 1900 Canadians die every year because of such serious adverse events.
While this is not an efficacy study, we do look to the fact that patients are actually purchasing PENNSAID(r) in the open label trial as a kind of "market validation" of the product. No drug plans will cover the cost of an experimental drug and we cannot afford to provide the drug for no cost given the numbers enrolled. Therefore, for a patient to participate in the trial, they have to visit a specific physician, then go to a particular pharmacy and then reach into their pocket and buy the drug.
Study #107-96 has not been published. No submission has yet been made to a journal.
Insofar as the persuasiveness of the data, we will defer to the regulatory agencies to make their decision before weighing in with the quality of results. For now, we would point out that all three agencies (FDA; MCA; HPB) have accepted our submission for review. The goal we have before us is to obtain marketing approval from these agencies and that is where our efforts have been
focussed.
Sincerely,
Peter Block
Investor Relations Manager
Sorry for the length,
Jeff C |
