GlaxoSmithKline says that interim data from a major diabetes study shows no significant difference between the firm’s Avandia and standard therapy when it comes to cardiovascular risks, but acceptance of this view is far from universal.
The UK drugs giant claimed that the findings from an interim analysis of its 4,447-patient RECORD trial, which have been published by the New England Journal of Medicine, “adds further evidence to the overall cardiovascular safety profile” of Avandia (rosiglitazone). This follows the meta-analysis, also published by the NEJM, which a fortnight ago suggested that the drug might significantly increase the risk of heart attacks.
The study compares cardiovascular hospitalisation and death in patients treated with Avandia dual therapy (rosiglitazone plus metformin or sulfonylurea) and in patients treated with metformin and sulfonylurea in combination. After following patients for an average of 3.75 years, the interim analysis (the study is scheduled to end in late 2008) found the risk of heart failure was 2.15 times higher among patients in the Avandia group, compared to those who did not receive the drug. Additionally, 217 patients in the Avandia group were hospitalised or died from cardiovascular events, compared with 202 taking metformin and sulfonylurea in combination.
GSK did state, however, that a significant difference between the Avandia and control groups was seen only in the secondary outcome of congestive heart failure, where significantly more cases were seen in Avandia patients – “consistent with the well known association between fluid retention and thiazolidinediones,” the class of medicine to which rosiglitazone belongs.
Moncef Slaoui, chairman of R&D at GSK, said the RECORD data “add to the weight of evidence, from both previously published long-term clinical trials and other studies, that the overall ischemic cardiovascular safety profile of Avandia is comparable to the traditional anti-diabetes treatments. Patients and physicians should find these data reassuring.”
However, in an editorial in the NEJM accompanying the study, David Nathan, director of the diabetes centre at Massachusetts General Hospital, did not seem reassured. He claimed that the interim data "failed to provide exculpatory evidence" for the safety of Avandia, noting that while there were "too few heart attacks and other complications to definitively implicate or clear the drug...the results of this underpowered interim analysis suggest a possible adverse effect of treatment… rather than the benefit that was hypothesised."
The jury is still out on Avandia and the next episode of the saga will take place later today when a US House of Representatives committee questions US Food and Drug Administration Commissioner Andrew von Eschenbach, Dr Slaoui, and Steve Nissen, who authored the original meta-analysis linking Avandia to a 43% higher chance of having a heart attack.
Strong data for Cervarix at ASCO
Better news for GSK came at the American Society of Clinical Oncology meeting where the company unveiled data for its cervical cancer vaccine Cervarix which stated that the jab produced an immune response in 100% of women up to 55, after 18 months of initial vaccination.
517 women aged 15 to 55, who had received three doses of the vaccine as part of an initial late-stage trial, participated in the follow-up which showed that all of them had antibodies against human papillomavirus types 16 and 18, the two most common causes of cervical cancer. Cervarix, which is under review with both US and European regulators, will compete with Merck & Co’s Gardasil if it gets the regulatory go-ahead.
Massive Phase III trial for lung cancer vaccine
GSK also said that it has initiated a Phase III trial for an experimental vaccine for people with non-small-cell lung cancer. The study will enrol about 2,270 patients who have cancers expressing a tumour-specific antigen known as MAGE-A3, which is present in approximately 35% to 50% of early NSCLC cases.
This follows positive Phase II data presented at ASCO which showed a 27% reduction in the relative risk of cancer recurrence following surgery in patients who received the vaccine, compared with those who received placebo.