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European Commission Sends GSK's Tyverb Back to CHMP Over Liver Safety Concerns
19 Mar 08
Concerns over hepatotoxicity have prompted a further review of breast cancer drug Tyverb by the CHMP, delaying the hotly anticipated EU market launch by several months.
Global Insight Perspective | | Significance | The European Commission has asked the CHMP to review some new clinical and post-marketing data on GSK's breast cancer drug Tyverb (lapatinib), before any potential marketing approval can be granted. | Implications | The data suggest a small risk of hepatotoxicity among patients administered Tyverb. GSK says this can be easily monitored through regular blood tests, and has urged healthcare practitioners to recommend this in countries where the drug is already approved. | Outlook | The CHMP will discuss the findings in mid-April, delaying possible EU approval for Tyverb and reducing its chances of competing with Roche's Herceptin (trastuzumab) on the market for now. |
The European Commission has thrown an unexpected delay into GlaxoSmithKline's (U.K.) plans for speedy European Union (EU) approval for Tyverb (lapatinib), after referring the breast cancer treatment's marketing authorisation application (MAA) back to the European Medicines Agency (EMEA) for further review. The EMEA's Committee for Medicinal Products for Human Use (CHMP) had recommended conditional marketing approval for Tyverb back in December, and had forwarded the MAA on to the Commission for a final verdict (see United Kingdom: 17 December 2007: FDA Delays Cervarix Launch in the U.S. While EMEA Hurries Tyverb Market Access). GSK was seeking European approval for Tyverb in combination with capecitabine as a treatment for patients with advanced or metastatic breast cancer whose tumours over-express the Erb2 (HER2) receptor protein, and who have already been treated with either anthracyclines, taxanes or trastuzumab. The Commission's decision came after GSK presented it with new data from a pharmacovigilance review of Tyverb, which included findings from clinical trials and post-marketing data from countries where the drug has already been approved. According to GSK, the results of the pharmacovigilance review included the discovery of a small risk of hepatotoxicity during treatment with Tyverb. Hepatotoxicity is characterised by elevated levels of liver enzymes that can attack or damage the liver, and in the case of Tyverb incidence of the condition was recorded at four per 1,000 patients evaluated during the review. The company says it has informed investigators running ongoing clinical trials on Tyverb and prescribers in countries where the drug is already on sale that they should increase the frequency of blood tests administered to patients to monitor liver function. The CHMP has been informed by the European Commission that it must discuss these latest findings before a final adoption of its approval recommendation can be issued. The matter is due to be reviewed at the CHMP's next meeting on 21-24 April. Tyverb saw its first market launches in 2007 under the brand name Tykerb, and brought in turnover of £51 million (US$102.4 million) by the end of the year. GSK has previously said that it expects Tyverb/Tykerb to generate global revenues of US$1.35 billion by 2010. Outlook and Implications This is not the first time that GSK's latest cancer hopeful has been linked to adverse effects, as the U.S. FDA rapped the company's knuckles last year over its apparent failure to adequately warn prescribers that Tykerb is known to decrease left ventricular ejection fraction (LVEF), and that patients' LVEF should be monitored before and during treatment (see United Kingdom: 27 November 2007: GSK Receives FDA Warning Letter Over Launch of Tykerb). The main difference between this and the European Commission's decision is that Tyverb has not yet been approved in Europe, and as such GSK still has everything to play for. The fact that hepatotoxicity levels can easily be monitored with routine blood tests should be a point in Tyverb's favour, and the drug's proven efficacy in reducing the progression of HER2-positive breast cancer, where Herceptin (trastuzumab; produced by Swiss company Roche) has failed, is also a convincing argument for approval. HER2-positive patients make up approximately 20% of all breast-cancer patients, and the pressure from patient groups to approve and subsidise new treatments is enormous. Approval for Tyverb in Europe still remains likely, even if it is somewhat delayed. However, in light of the latest safety data it remains to be seen whether GSK will eventually seek marketing approval for the drug as a first-line treatment.
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