New melanoma drug in the pipeline from Plexxikon and Roche

By Dr. Ananya Mandal, MDSep 9 2010

Researchers from biotech company Plexxikon have found that their candidate drug for skin cancer melanomas can be administered more effectively in early stages of the disease.

This experimental drug PLX4032 has already shown its prowess in an early clinical trial of melanoma patients, shrinking advanced melanoma tumors in 81 percent of 32 patients with the fatal skin cancer. The drug turns off the proteins that drive cancer cell growth, significantly reducing the size of the tumors. In one case the tumors were completely erased. The study was published in the journal Nature.

Gideon Bollag of the California-based company, who was the lead researcher said, “Looking at the biopsies from patients before treatment and two weeks after, we show we can inhibit the target directly in the tumor.” He explained that the drug had to almost completely block a chemical pathway in the tumor cells to reduce the size of the tumors in the melanoma patients “Perhaps most surprisingly and interestingly, we needed to inhibit the target almost completely in order to demonstrate tumor shrinkage in the melanomas of the patients,” he added. He explained, “To understand exactly how compounds are working, it's really important to analyze the biopsies.”

The company now is working in collaboration with Roche to develop a companion diagnostic test that will help identify patients with what is called the BRAF mutation. These patients are the most likely to benefit from the compound. Plexxikon's drug, which is being co-developed by Roche, only works in the 50 to 60 percent of melanoma patients who have a specific mutation of the BRAF gene.The U.S. Food and Drug Administration is looking at the evidence to approve and validate such diagnostic tests. “We think this might be the first example where the therapy and the diagnostic go to the FDA at the same time,” Bollag said.

According to Kathleen Glaub, Plexxikon's president, similar research is on towards developing another compound that can treat cancers that have spread to the bone, including breast cancer. “I think all of us in this industry have to figure out different ways to develop drugs that are more efficient and enable us to move development faster,” said Ms Glaub. She added that the company expects to present results of its phase 2 study in November at an international melanoma conference.

According to Bollag, the company would embark on a clinical trial that will combine PLX4032 with a Roche drug called GDC-0973 that interferes with the MEK signaling pathway, which is also attacked by PLX4032.