Regulators in Europe have granted marketing authorisation, albeit conditionally, to GlaxoSmithKline's breast cancer compound Tyverb.

Following a postive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) at the end of April, the European Commission has backed Tyverb (lapatinib) to be used in combination with Roche's Xeloda (capecitabine). The approval covers patients with HER2-positive advanced or metastatic breast cancer, and GSK noted that people taking the combo should have progressive disease following therapy with anthracyclines and taxanes, as well as Roche's Herceptin (trastuzumab) in the metastatic setting.

Tyverb, sold in the USA as Tykerb, is a small molecule and has the convenience of being administered orally, unlike Herceptin which is injected. It works by getting inside the cancer cell and inhibiting two receptor proteins – the tyrosine kinase components of the ErbB1 and ErbB2 receptors. The signalling of these receptors is responsible for tumour growth and proliferation.

The approval is based on a pivotal Phase III trial which demonstrated that lapatinib when given in combination with capecitabine significantly increased time to progression by 27.1 weeks compared to 18.6 weeks with Xeloda alone. However the approval is conditional, which means that GSK needs to provide further clinical data, including an investigation into Tyverb’s potential effect on reducing the incidence of brain metastases, one of the most common sites of relapse.

The firm added that in an exploratory retrospective analysis from the pivotal study, there was a significantly lower incidence of CNS metastases as the first site of relapse with lapatinib plus capecitabine, compared with Xeloda alone (4 vs 13 patients). Further data from the trial needs to be provided and an additional study will be conducted.


Less welcome for GSK was the news that US Senator Charles, an outspoken critic of the pharmaceutical industry and its regulators, has asked the Food and Drug Administration to investigate whether the firm withheld data about a risk of suicide linked to the antidepressant blockbuster Paxil/Seroxat (paroxetine).

In particular he wants the FDA to look at a report prepared by Dr Joseph Glenmullen, a professor of psychiatry at Harvard University, which asserts that GSK had to know of Paxil’s suicide risk when it sought approval for the drug. He also asked the regulator to consider the UK’s Medicines and Healthcare Products Regulatory Agency’s recent report on Seroxat, which was four years in the making and criticised the company’s practices.

Sen Grassley said “the British counterpart to our country’s FDA found that GSK withheld important safety data” on the drug. "If the company engaged in this behaviour in the UK, then I want to make sure that the same didn't happen here in the US”, he added.

The senator asked GSK about the Glenmullen report last February and the firm believes it responded fully to his questions. When the aforementioned report came out, the company was dismissive of his findings and said that Dr Glenmullen “carefully selected excerpts from GSK documents and made his own interpretations without looking at the totality of the data”.