Side-effect caution to delay Tyverb
pharmafile | March 19, 2008 | News story | Research and Development |Â Â Â
GlaxoSmithKline has informed regulators in the US and Europe that a small number of patients taking its new breast cancer drug Tyverb have suffered liver side-effects.
Already launched in the US, Tyverb (lapatinib) had been awaiting final clearance from Europe's regulator, but will now be reassessed by the EMEA in late April before it can be approved.
Tyverb (known as Tykerb in the US) has been expected to be GSK's first blockbuster in cancer, and could still reach peak sales of around $2.5 billion.
GSK said it believes the data doesn't change the positive benefit-risk profile for Tyverb, but the news is a setback for a key product in the company's late-stage pipeline.
The company uncovered the side-effects in the review of clinical trial and post-marketing data, finding that a small number of patients can suffer hepatotoxicity (predominately elevated liver enzymes) when taking Tyverb.
Severe hepatotoxicity was less frequently observed, and elevated liver enzymes generally returned to normal when the patients stopped taking Tyverb.
The side-effects affected only 0.4% of patients (or four per 1,000) and the events were generally identified through a routine blood test, but an increasingly cautious approach from regulators means all known side-effects must be closely evaluated.
Despite the relatively small number of patients affected, the news is a blow to Tyverb's prospects. Not only will the new EMEA review hold back the already delayed launch of the drug, it will raise doubts about the drug's safety before it mounts its challenge to existing cancer treatments.
Tyverb is being launched as a treatment for advanced or metastatic breast cancer in combination with Xeloda (capacitabine), and will eventually challenge Roche's top-selling breast cancer drug Herceptin.
The most common adverse events in trials of lapatinib plus capecitabine during trials were gastrointestinal (diarrhoea, nausea and vomiting) or skin disorders (rash and hand and foot syndrome).
There were also some reports of decreases in left ventricular ejection fraction (LVEF) and also pulmonary toxicity, though these side-effects are also seen in patients taking Herceptin.
Tyverb was set to gain a conditional approval from the EMEA, which means the regulator would wait until after its launch for key efficacy data.
A conditional approval could make it difficult for GSK to promote the drug, as it will involve the regulator reviewing new information annually and updating the product information as necessary.
