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12:00 AM
Oct 17, 2011
 |  BioCentury  |  Product Development

Tremelimumab, take three

MedImmune faces new hurdles with tremelimumab since Pfizer dropped in melanoma

Three years after Pfizer Inc. discontinued development of tremelimumab for melanoma, AstraZeneca plc's MedImmune LLC unit has in-licensed the mAb. Poor design may have tripped up Pfizer's Phase III, but given that two new melanoma drugs have entered the market since then, MedImmune would have to do more than run a better study to advance the mAb for the indication.

Last week, MedImmune received worldwide rights to develop and commercialize the mAb against CTLA-4. Pfizer retained rights for undisclosed combination therapies.

By binding CTLA-4, tremelimumab blocks the receptor from interacting with its ligands CD80 (B7-1) and CD86 (B7-2). Blockade of CTLA-4 augments T cell activation and proliferation.

Pfizer was developing tremelimumab for melanoma, but discontinued work in 2008 after interim Phase III data (Study A3671009) showed the mAb would not improve overall survival, the primary endpoint, vs. dacarbazine or temozolomide in chemotherapy-naïve, advanced melanoma patients.

In January 2010, Pfizer revived the program in a co-development deal with Debiopharm Group. The Swiss company was responsible for Phase III testing and planned to use an undisclosed biomarker to enroll patients most likely to respond to tremelimumab.

The program never got off the ground, as Debiopharm returned the rights that same year. According to Debiopharm spokesperson Maurice Wagner, the company did not believe tremelimumab "added therapeutic value" in melanoma.

Now MedImmune is taking a crack at the antibody, but is saying little about its plans. It faces a more complicated treatment environment as two drugs have been added to the armamentarium this year.

In March, FDA approved Yervoy ipilimumab from Bristol-Myers Squibb Co., another mAb against CTLA-4, as a monotherapy to treat first-line metastatic melanoma (see BioCentury, April 11).

In August, FDA approved Zelboraf vemurafenib from Roche and its Genentech Inc. unit to treat unresectable or metastatic melanoma with the BRAF V600E mutation, which is found in about half the metastatic melanoma population (see BioCentury, Aug. 22).

When it announced the deal, MedImmune said it will "explore tremelimumab in a number of potential cancer indications."

Doctors contacted by BioCentury had a few suggestions on what went wrong with the melanoma program and how MedImmune might be able to revive the antibody in light of these new treatment options. The clinicians...

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