Released by FDA: 9/5/00.  Posted by FDA:  9/8/00

Synsorb Biotech Inc. 
John J. Frey. Ph.D. 
Vice President Clinical and Regulatory Affairs

c/o Arthur Y. Tsien 
Olsson, Frank and Weeda, P.C. 
Attorneys at Law 
Suite 400 
1400 Sixteenth Street. N.W. 
Washington, D.C. 20036-2220

RE:   IND# [confidential, deleted by FDA]
        SYNSORB Pk 
        MACMIS ID # 9264

Dear Mr. Tsien:

As a part of the Division of Drug Marketing, Advertising, and Communications’ (DDMAC) routine surveillance, we have reviewed two press releases on the website for Synsorh Biotech Inc.’s (SBI) product SYNSORB Pk¹.  In the two press releases, SBI promotes SYNSORB Pk as safe or effective for the prevention of progression to Hemolytic Uremic Syndrome (HUS) in children infected by E. coli.  We find the press releases in violation of the Federal Food, Drug, and Cosmetic Act and its applicable regulations. Specifically. we object to the following:

Pre-Approval Promotion

SYNSORB Pk is an investigational new drug that has not been approved by the Food and Drug Administration as being safe or effective.  SRI has promoted SYNSORB Pk as safe or effective prior to approval for the treatment of HUS in children infected by E.coli.

For example, in the July 12, 2000 press release, SBI reported results on their planned interim analysis, which showed a limited trend toward efficacy and did not successfully meet the defined protocol objectives.  However, SBI also provided misleading statements and conclusions from an unplanned subgroup analysis. which included:

• Approximately one third of the patients were treated within 2 days of the onset of their symptoms and data from this sub-group of 152 patients demonstrated a statistically significant (p<0. 05) lower rate of HUS for SYNSORR Pk compared to placebo. 

• We are very excited to see statistically significant clinical data for SYNSORB Pk in this sub- group of children. 

• The drug appears to offer substantial benefit to patients when treatment is started during the first 2 days of their symptoms. 

• Given the findings in this subgroup, SYNSORB has determined that it would not be appropriate to continue recruiting patients in the current trial until the Company has engaged with the regulatory authorities to discuss options for concluding the program.

These misleading statements regarding the significance of the unplanned sub-group analysis are reiterated in a press release dated August 3, 2000, which include:

• We have recently reported interim data showing that SYNSORB Pk can reduce the progression of HUS in children when administered within the first 2 days of diarrhea symptoms. 

• Outcomes of an interim analysis of the SYNSORB Pk Phase III data announced previously revealed that when administered within 48 hours of symptoms, the product reduced the progression to HUS in children by 59%.  As a result, SYNSORB is engaging with the regulatory authorities to obtain feedback regarding the best strategy to successfully complete the development of SYNSORB Pk

Failure to Present Material Facts

In addition, SBI presents misleading statements that fail to disclose facts that are material in light of representations made about SYNSORB Pk.  SBI presents the results from the Phase III trial interim analysis that revealed that in 526 children treated within 5 days of the onset of symptoms, there was a limited trend toward efficacy, and the trial failed to meet designed protocol objectives . However, SBI then presented a sub-group analysis, which evaluated 152 children treated within two days of the onset of symptoms.  SB1 concluded that there was a statistically significant (p<0.05) lower rate of HUS for SYNSORB Pk compared to placebo.  This presentation is misleading because the sub-group analysis was not part of the original Phase III study design, did not demonstrate a. definitive finding, and may have occurred purely by chance.  SBI implies that the sub-group analysis showed significant findings to complete the development of SYNS ORB Pk when in fact, in discussion with FDA, it was determined that appropriate studies are needed to determine safety or efficacy. 

Requested Action

We request that SBI immediately cease dissemination of materials and activities that contain these and similar representations, and conclusions concerning the safety or efficacy of SYNSORB Pk.  In addition, we request that SBI submit a written response on or before September 12, 2000 describing its intent and plans to comply with the above.  The response should include a list of materials discontinued and the date on which these materials were discontinued.

You should direct your response to the undersigned by facsimile by at (301) 594-6759, or to the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm 1 7-B-20, 5600 Fishers Lane, Rockville, MD 20857. We remind you that only written communications are considered official.

In all future correspondence regarding this particular matter, please refer to MACMIS ID # 9264 in addition to the IND number.

Sincerely,

James R. Rogers, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
      Advertising, and Communications

____________________________________________________

¹  Press releases dated July 12, 2000 and August 3. 2000. from the Synsorb Riotech Inc. website:  http://www.synsorb.com (August 4, 2000).