Biotech Values

[mcbio]

Re: BioMS

"<<I had posted something (little) on them probably a couple years ago if you have search. I don't recall much but there was a good analysts report or article I read that talked about how the drug was supposed to work and didn't like its chances which discouraged me from seriously considering it. I kept watching them though but never close to buying>>."

I wasn't able to find your post using various keywords (BioMS, bomsf, dirucotide, etc.) but perhaps that is due more to my lacking search skills than anything else. ; )

I guess as far as not liking the chances of the drug working, I wonder if the article was older and before they had released any trial results for their MS drug. I'm by no means an expert in interpreting MS trial results, but the actual clinical results so far look pretty good.

First, here's a link to their Web site: http://www.biomsmedical.com/

Second, they have press releases on their Web site going back to 2003. Here's a link back to a release on 5/23/03 where they released final Phase II results for Dirucotide in Primary or Secondary Progressive MS patients: http://www.biomsmedical.com/display-press-release.php?id=28

"BioMS Medical Corp (TSX: MS) today announced positive final results from its Phase II clinical trial for the treatment of multiple sclerosis (MS) with its synthetic peptide MBP8298. The MBP8298 peptide is designed to reduce the disease-associated production of a group of anti-MBP antibodies that are reactive with the central nervous system.

The 4 year Phase II trial enrolled 32 patients with either Primary or Secondary Progressive MS. The study had two phases, a two-year randomized double-blinded, placebo-controlled phase, followed by a two-year open label phase. During the double-blinded phase patients were given 500 mg of the MBP8298 peptide intravenously every 6 months. Data from the trial was analyzed both in terms of overall results, and in terms of a genetic sub-group of patients who carried either HLA-DR2 or HLA-DR4 immune response genes (“DR2/4”). These genes are associated with T-helper cells involved in the production of anti-MBP antibodies targeted by the MBP8298 peptide.

Whereas the incidence of DR2/4 genes in the normal population is relatively low, in the MS population patients that have either the DR2 or DR4 genes account for approximately 75% of the estimated 2 million MS patients worldwide. Of 32 patients enrolled in the double-blinded phase of the trial, there was a representative sample of 20 patients that carried either the DR2 or the DR4 genes, and these were evenly divided between patients dosed with MBP8298 (n=10) and placebo (n=10).

Statistically Significant Results in Patients with HLA-DR2 or HLA-DR4 Genes Clinical progression was measured by changes in score on the Expanded Disability Status Scale (“EDSS”), as the primary clinical indicator. EDSS is used to assess patients’ ability to function on a scale of 0 to 10. Patients were considered to have progressed if they had a confirmed change in EDSS of greater than or equal to 1.0 when their baseline score was less than or equal to 5.0, or a change of greater than or equal to 0.5 when their baseline score was greater than or equal 5.5.

At the end of the double-blinded phase, 0 out of 10 (0%) of the DR2/4 patients on MBP8298 progressed on EDSS as compared to 6 out of 10 (60%) of the patients on placebo (Fisher’s Exact test p=0.0108).
“Potentially delaying the debilitating progression of MS represents a major step forward in the treatment of MS,” said Mr. Kevin Giese. “A 100% stabilization rate over a two year period in the DR2/4 group exceeded our expectations.”

At the end of the open label phase, only three of the DR2/4 patients on MBP8298 (30%) had progressed at 42 months, meaning that the median time to confirmed progression for the MBP8298 patients is at least four years as compared to that of the placebo patients which was 2 years (Log Rank test p=0.004). The results were equally valid for both Primary and Secondary Progressive MS patients.

In terms of safety, patients on MBP8298 showed no statistically significant difference from the placebo group in terms of adverse events, use of steroids or in the results from eight different MRI tests. No treatment-related serious adverse events were recorded in the patients receiving MBP8298, providing further confirmation of the drug’s safety and tolerability.

Results in the Total Population

The 32 patients in the double blinded phase were made up of 16 patients that received MBP8298 and 16 that received placebo. In terms of EDSS, only 5 out of 16 patients on MBP8298 progressed as compared to 9 out 16 patients on placebo, which constitutes a 44% reduction in progression (Fisher’s Exact test p=0.29). Similarly, in terms of the two secondary clinical outcomes, the 22 meter Timed Walk and Foot Taps, both the overall and DR2/4 sub-group results showed patients on MBP8298 scoring better than placebo, although not with statistical significance. There were no statistically significant results on any safety parameter, nor was there any serious MBP8298-related adverse event.

My thoughts:

Admittedly, this is a very small trial as it only included 32 patients. And of these patients, only 20 carried one of two genes for whom such sub-group the drug is intended to work. These 20 were then divided to half receiving the drug and half receiving placebo.

My main question would be whether or not the Expanded Disability Status Scale that BioMS used to measure the results is the de facto standard in MS trials or is it some obscure measure. Also, I'll put some stock in the results out to two years as these were double-blind and placebo-controlled. 0 of 10 patients on the drug progressed according to EDSS compared to 6 of 10 on the placebo and this was statistically significant. However, how much can we rely on the results past two years as these are based on an open label?

Also, the results in the total population were better for the drug compared to placebo but not statistically significant. However, since the drug is targeted to the sub-group of MS patients that contain 1 of 2 specific genes, and trial results were statistically significant regarding primary outcome in this sub-group, I don't believe this would be of great concern.

I would question how important the secondary measurements of 22-meter timed walk and foot taps are as the drug results were not stasticially significant compared to placebo, even in the sub-group of MS patients for which the drug is targeted.