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12:00 AM
 | 
Jul 19, 2010
 |  BioCentury  |  Product Development

The tanezumab surprise

What may be behind surprise worsening of symptoms in Pfizer's trials of tanezumab

Pfizer Inc.'s tanezumab has produced contradictory and not immediately explicable data this summer - first meeting the primary endpoints in a Phase III trial in osteoarthritis patients and shortly thereafter being placed on hold by FDA after some OA patients receiving the anti-nerve growth factor antibody actually had a worsening of symptoms. It's still unknown whether the issue relates to trial design or the antibody's mechanism, but doctors now think companies developing anti-NGF mAbs may need to start monitoring OA progression in their clinical trials.

Last month, Pfizer reported that all three doses of IV tanezumab every eight weeks met the co-primary endpoints in a U.S. Phase III trial in 690 patients with pain due to OA of the knee. The endpoints were significant improvements in mean Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale and Patient Global Assessment (PGA) score from baseline at week 16 vs. placebo.

The 2.5, 5 and 10 mg tanezumab doses improved WOMAC Pain subscale scores by 3.15, 3.26 and 3.62 points, respectively, vs. 2.42 points for placebo (p=0.015, p=0.005 and p<0.001). Low-, middle- and high-dose tanezumab improved WOMAC Physical Function subscale scores by 2.8, 3.02 and 3.29 points, respectively, vs. 2.04 points for placebo (p=0.009, p<0.001 and p<0.001).

On the PGA endpoint, 2.5, 5 and 10 mg tanezumab improved scores from baseline by 0.83, 0.87 and 1.01 points, respectively, vs. 0.51 points for placebo (p=0.001, p<0.001 and p<0.001). Data were presented at the European League Against Rheumatism meeting in Rome.

The problem came a week later when Pfizer suspended its OA program for tanezumab after FDA placed the OA trials on clinical hold because a small number of patients treated with the humanized mAb experienced a worsening of their OA symptoms that led to joint replacement surgery. The pharma said one of the cases was in the recently reported U.S. Phase III trial.

In total, Pfizer is running 13 Phase III trials of tanezumab for OA - 10 with IV dosing and three with subcutaneous...

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