Novartis/Schering drug falls at clinical hurdle
an ongoing clinical trial suggested that it was unlikely to boost
survival rates of patients with colon cancer. This is the second
setback for the drug this year, which Novartis is co-developing
PTK/ZK is just one of a new generation of designer drugs tailored to block errant kinases, which is now coming down industry pipeline. Acting like relay switches within cells kinases are involved in turning on basic operations such as cell division. When kinases malfunction, cancer growth can occur. A new generation of designer drugs tailored to block errant kinases is now coming down industry pipelines.
PTK/ZK, an investigational oral multi-VEGF receptor tyrosine kinases inhibitor, blocks tumour angiogenesis and lymphangiogenesis by inhibiting all known VEGF receptors.
The latest news is a blow for the two drug companies but its rivals Genentech and Roche will be encouraged by the development. In February 2004, Genentech and Roche won the race to get the first such "anti-angiogenesis" cancer drug, the intravenously-administered Avastin, on the market.
Novartis and Schering have hopes that PTK will compete with Avastin, which is considered one of the biggest advances in cancer therapy in recent years and could see its total sales top $5 billion (€4 088 billion).
In the CONFIRM 2 trial, the overall side effects that were seen were generally consistent with that of CONFIRM 1. These included an increased incidence of nausea, hypertension, dizziness and thromboembolic events in the PTK/ZK arm of the study.
The Phase III CONFIRM 2 trial was designed to evaluate the potential overall survival benefit of once daily oral treatment with PTK/ZK in combination with chemotherapy (FOLFOX-4 regimen) as second-line therapy in patients with metastatic colorectal cancer.
Despite the disappointment, Novartis and Schering said that they would continue their two large, phase 3 trials with PTK but would review development plans in light of the new data. The companies had been expected to seek FDA approval for PTK in 2007 after completing the two phase 3 trials next year.
A spokesman for Novartis told DrugResearcher.com: "CONFIRM 2 will continue with additional results expected in mid-2006. It is important to note, at this time, only a small number of patients in the CONFIRM 1 & 2 studies remain on treatment."
"In fact, the majority of patients are now being followed primarily for overall survival. Treatment decisions for specific patients are will continue to made by the investigators, in consultation with their patients, after assessment of individual benefit and risk," he commented.
The spokesman added that the decision to disclose the CONFIRM 2 data would not impact CONFIRM 1, which would continue as planned with final overall survival results expected in the second half of 2006.
"Due to the low probability of reaching the primary endpoint, the filing strategy in metastatic colorectal cancer has to be reevaluated. The filing strategy in metastatic colorectal cancer will be reevaluated based on full analysis of the data. No specific timeline has been announced," he added.
In March this year, interim data from another trial showed that the drug, earlier seen as a potential breakthrough medicine, had failed to significantly improve tumour progression rates in advanced colon-cancer patients.