Trubion's RA Candidate Gets the Chop in Pfizer's R&D Cull

June 15, 2010 Trubion's RA candidate gets the chop in Pfizer's R&D cull

Amy Brown

The decision by Pfizer to scrap one of Trubion Pharmaceuticals' rheumatoid arthritis (RA) candidates is, unfortunately for the small US biotech, not hugely surprising. The products were gained as part of the Wyeth merger and as EP Vantageidentified last year appeared vulnerable to an R&D cull (Wye-Pfi R&D cull poses a threat to licensing deals, October 20, 2009).

The companies announced last night that TRU-015 failed to meet the primary endpoint of a large phase IIb trial and although efficacy was seen the product would probably not be sufficiently commercially differentiated to justify further investment. The blow was softened by confirmation that work on another drug being developed as part of the deal, SBI-087, will continue, but the situation highlights that Pfizer is serious about trimming its research budget and this remaining candidate needs to really impress to avoid the same fate.

Superior profiles

Trubion originally signed a deal with Wyeth back in early 2006, to discover and develop novel biopharmaceuticals to treat inflammatory disease and cancer, utilising the smaller partner’s proprietary small modular immunopharmaceutical (SMIP) technology. SMIPs are smaller than antibodies which exhibit selective binding and have long half lives, leading to slower metabolism and, the company hopes, less frequent dosing.

The compound initially chosen for development was the CD20-targeted TRU-015, which at the time was in phase II for RA.

Trubion had hoped that the phase IIb trial, started in early 2008, would be supportive of a registration package. The study was randomised, double-blind and placebo-controlled, seeking to evaluate the safety and efficacy of two doses of the drug in around 216 patients with active seropositive RA, who were already on methotrexate. The open label extension has gone on for some time, retreating patients with the higher dose of the drug that seemed to exhibit the best efficacy.

Although an interim analysis had suggested the trial was a success, ultimately an “internally predefined” primary endpoint was missed, seemingly because of a greater than usual placebo response.

Strong incumbent

Still, with Roche’s anti-CD20 antibody Rituxan already on the market and others including GlaxoSmithKline’s Arzerra already attempting to get in on the act, and notably more advanced than TRU-015, startling efficacy was going to be needed to justify taking what could have ended up looking like another me-too Rituxan into phase III trials.

The omens were not good; in early 2008 Wyeth decided against developing TRU-016 in lupus and NHL, and other oncology indications, after reviewing the competitive landscape for CD20-directed therapies.

In the hands of Wyeth this candidate may still have been progressed in RA, the company was essentially looking for an Enbrel replacement, which loses patent protection in 2012.

Pfizer, however, already has a phase III RA candidate, in the shape of JAK inhibitor CP-690,550, where the company has clearly decided to place its bets for this indication, at the moment. Even with a lot of research going on in RA, the Jak inhibitor is looking like one of the most promising late-stage RA candidates around at the moment (Therapeutic focus - Rheumatoid arthritis pipeline full but deals dropping off, July 10, 2009).

Enhanced potency

Still, the companies will continue to work on SBI-087, a second candidate generated via the original Wyeth deal. This candidate was selected in early 2008 for clinical trials on the basis of research that suggested the fully humanised CD20-directed SMIP had enhanced potency in B-cell depletion compared to Rituxan and other CD20-directed therapies. However the dominance of Rituxan means any new CD20-targeted candidate is going to have to show very encouraging signs of efficacy. According to clinicaltrials.gov a phase II trial of the drug in RA could report in June next year, which will be closely watched, whilst phase I data in lupus might be available earlier.

With the research collaboration between Wyeth, now Pfizer, destined to end in December, Trubion will be hoping the end of TRU-015 does not spell the end of the deal all together.

Shares in the company dropped 11% to $3.25 in early trade today, suggesting investors are worrying about the same thing.