Genzyme's Clostridium difficile diarrhea candidate tolevamer missed its non-inferiority endpoint in a Phase III study that compared it with vancomycin in a North American population, the company reported July 6.

A second identical three-arm study comparing liquid tolevamer with vancomycin (the primary endpoint) and metronidazole in a primarily European and Australian patient population is fully enrolled, with results due by the end of the year. Together, the studies, which enrolled 1,100 patients at about 300 sites, are called Polymer Alternative for CDAD Treatment or PACT.

"We're disappointed with the results. We'll see what the other study comes in with at the end of the year, but we don't believe that tolevamer will be commercialized anytime in the near future," Genzyme told "The Pink Sheet" DAILY.

That sentiment was shared by JP Morgan analyst Geoffrey Meacham, who wrote in a July 6 note, "We view the tolevamer program as dead given that a low threshold of non-inferiority was not met in trial 301. ... We do not have high hopes for the second Phase III trial, where even in the event of a positive result, the approvability looks unlikely. We would not be surprised to see tolevamer development discontinued by" the end of the year.

Genzyme had projected a 2008 launch of the novel therapy, pending a positive study outcome (¹ Also see "Genzyme Tolevamer Represents New Market Opportunity" - Pink Sheet, 14 February, 2007.). The current results are contrary to Phase II studies in which a solid oral dosage of tolevamer proved non-inferior to vancomycin, the company noted.

Tolevamer is a non-antibiotic polymer designed to bind and neutralize toxins released by C. difficile that damage the intestine. PACT is the largest C. dif trial ever conducted and the first to test the efficacy of the standards of care, Genzyme said. Data from the first study will be presented at a future medical conference.

Poor results for tolevamer mark the third pipeline setback for the biotech in a month.

In June, the company announced mixed results from two studies comparing a powder form of Renvela (sevelamer carbonate), a follow-on to Renagel (sevelamer hydrochloride) for the control of serum phosphorus in patients with chronic kidney disease on dialysis (² Also see "Genzyme Gets Mixed Results On Renvela Powder Formulation" - Pink Sheet, 18 June, 2007.).

An NDA for the tablet form of Renvela submitted in December is pending at FDA (³ Also see "Genzyme Will Look To Differentiate Renvela With Improved Dosing" - Pink Sheet, 21 December, 2006.). The company anticipates a late 2008 launch for Renvela, which is also being studied in CKD patients not yet on dialysis.

On July 5, Genzyme announced that its next-generation lubricative treatment for osteoarthritis of the knee, hylastan, had failed to prove superior to treatment with corticosteroids. The company said it would focus on approval and launch of the single-treatment form of its established viscosupplement Synvisc (hylan G-F 20) (⁴ Also see "Genzyme Next-Generation Osteoarthritis Candidate Hylastan Found Not Superior To Steroids" - Pink Sheet, 5 July, 2007.).

Genzyme submitted the application for Synvisc-One to FDA in February.

In May, Genzyme revised the timeline for taking its B-cell lymphocytic leukemia therapy Campath (alemtuzumab) into the multiple sclerosis setting. The company now anticipates moving the monoclonal antibody into Phase III for MS during the second half of this year, with a potential launch in 2011, two years off the original plan (⁵ Also see "Genzyme Campath MS Launch Could Be Delayed Two Years" - Pink Sheet, 2 May, 2007.).

- Shirley Haley (s.haley@elsevier.com)

Genzyme’s Tolevamer Misses Endpoint In First Of Two Phase III Studies

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