CHICAGO (Reuters) – Late-stage trials of two experimental skin cancer drugs from GlaxoSmithKline, each designed to block different pathways used by tumor cells, have found the drugs helped patients with fewer side effects than current chemotherapy.

Both drugs, trametinib and dabrafenib, were tested in patients with a mutation in a gene known as BRAF. About half of all melanomas, the deadliest form of skin cancer, have the genetic aberration.

Cancer occurs through genetic changes in cells allowing tumor growth factor receptors which activate various pathways, including a protein known as MEK. It is believed that BRAF-mutated melanomas should be particularly dependent on MEK, which is needed to amplify the cancer’s genetic signal.

Roche’s Zelboraf, or vemurafenib, is the only BRAF inhibitor currently approved for treating melanoma.

Latest results from a pivotal trial of the Roche drug, presented at a meeting in Chicago of the American Society of Clinical Oncology, found that it improved survival by nearly four months.

But 19 percent of patients on Zelboraf developed a less-deadly form of skin cancer known as cutaneous squamous cell carcinoma and 10 percent developed another type of non-malignant lesion. In addition, most patients eventually develop resistance to the drug.

Removing the non-cancerous lesions is not a huge problem, but a drug with fewer such side effects would be appealing, said Dr. Kari Kendra, a melanoma specialist at Ohio State University who was not involved in the studies.

“Anytime we don’t have to be intrusive is a benefit,” she said.

Citigroup has estimated Glaxo’s annual sales for dabrafenib and trametinib at 1.5 billion pounds ($2.35 billion) by 2020, some three times the average of analysts’ estimates.

Citi analyst Andrew Baum said dabrafenib was likely to be launched in 2013 and would quickly erode sales of Roche’s Zelboraf.

COMBINATION TREATMENT

In the trial of Glaxo’s trametinib, which is designed to interfere with MEK, patients given the drug lived for a median of 4.8 months before their disease worsened, compared with 1.5 months for patients treated with standard chemotherapy.

The drug was associated with a 46 percent reduction in the risk of death.

Side effects included skin rash in 7 percent of patients, eye problems and high blood pressure.

The trial of dabrafenib, a BRAF inhibitor, found that patients on the drug lived for a median of 5.1 months before their disease worsened, compared with 2.7 months for the chemotherapy patients.

Squamous cell carcinomas developed in 6 percent of the dabrafenib patients, and 3 percent of them had photosensitivity.

Last month Glaxo announced results from a mid-stage trial showing that patients treated with both trametinib and dabrafenib lived for a median of 7.4 months before their disease got worse. Two percent of patients developed squamous cell cancer and another 2 percent developed small pre-malignant lesions.

Glaxo is conducting a pivotal trial of the combination treatment and said it plans to file with the regulatory authorities for approval of both drugs as single agent therapies.

About 160,000 new cases of melanoma are diagnosed each year and 48,000 melanoma-related deaths occur worldwide each year.

(Editing by Greg Mahlich)