First fragment-based drug approved

Today marks history with the first FDA approval of a drug to come out of fragment-based screening. The drug is branded as Zelboraf (vemurafenib), but readers of this blog are probably more familiar with its previous name of PLX4032. Although widely expected to be approved, the FDA acted more than two months ahead of schedule. The drug targets a mutant form of BRAF and has received widespread media coverage because of dramatic clinical results showing that it extends life for patients with a particularly deadly form of skin cancer. FiercePharma has an article with links to several others.

The drug was discovered at Plexxikon and developed in partnership with Roche; Plexxikon was acquired earlier this year by Daiichi Sankyo. The PLX4032 story is a case study in how rapidly fragments can enable a program: initiated in Februrary 2005, it took just six years to reach approval. It’s also an example of starting with a profoundly unselective fragment and winding up with a very selective drug (see here for early discovery and here for characterization of PLX4032).

Although I claim no prescience, I did state back in 2008 that it would be nice if a fragment-based drug would be approved by 2011. But more importantly, it is worth pausing to remember that this is a victory not just for the field of fragment-based drug discovery, but for those patients afflicted with metastatic melanoma. In the end, that’s what this is all about.